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1038MO - Intracranial activity of encorafenib and binimetinib followed by radiotherapy in patients with BRAF mutated melanoma and brain metastasis: Preliminary results of the GEM1802/EBRAIN-MEL phase II clinical trial
- Ivan Marquez-Rodas (Madrid, Spain)
Abstract
Background
Systemic treatment for patients (pts) with
Methods
GEM1802 (NCT03898908) is a prospective phase II clinical trial that evaluates EB (450 mg pd E + 45 mg bd B) in pts with BMs during 56 days (d) followed by brain radiotherapy (RDT) and EB until disease progression. Two cohorts (C) were planned: C1 (N=48), asymptomatic pts; and C2, symptomatic pts (N=15). Primary endpoint is icRR after 56d of EB (before RDT) in C1. Secondary endpoints are extracranial RR, intracranial progression free survival (icPFS), PFS, overall survival and safety. In addition, this study will explore if RDT could improve the duration of response with EB.
Results
We report preliminary results of icRR for first 25 pts with response evaluation after 56d of EB. 14 pts from C1 and 11 from C2 were evaluable for this analysis. icRR was 64.3% and 63.6% in C1 and C2 respectively. Partial response (PR), complete response (CR), stable disease (SD) and progressive disease (PD) as well as G3-4 AEs are described in the table. 71.4% pts in C1 and 72.7% in C2 received RDT following first 56 days of EB.
C1 (asymptomatic) C2 (symptomatic) N 14 11 Previous systemic treatment (%) 21.4 18.2 Brain Target Tumor Burden (mean, mm) 34.5 54.3 % Number of BMs 1 50 27.3 2-3 42.8 45.5 >3 7.1 27.3 Extracranial disease 85.7 100 icRR (95% CI) 64.3 (35-87) 63.6 (31-89) PR 57.1 54.5 CR 7.1 9.1 SD 35.7 36.4 PD 0 0 6 month icPFS 70.1 64.3 Whole brain RDT 28.6 45.5 Radiosurgery/SBRT 50 33.3 Related G3-4 AEs 23.5 13.3
Conclusions
These results are in line with previous data reported for other targeted therapies in this setting, demonstrating a high response rate that is independent of symptomatic status of the pts. Based on this analysis, planned enrollment will continue until completion of accrual.
Clinical trial identification
NCT03898908.
Legal entity responsible for the study
Spanish Melanoma Group (GEM).
Funding
Pierre Fabre.
Disclosure
I. Marquez-Rodas: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Highligth Therapeutics; Financial Interests, Personal, Advisory Board: Bioline Rx; Financial Interests, Personal and Institutional, Invited Speaker, GEM1802 clinical trial: Pierre Fabre; Financial Interests, Institutional, Invited Speaker, GEM1801 clinical study: Novartis; Financial Interests, Institutional, Invited Speaker, GEM1801 clinical study: BMS; Financial Interests, Institutional, Invited Speaker, GEM1801 clinical study: Roche; Financial Interests, Institutional, Invited Speaker, GEM1801 clinical study: Pierre Fabre; Financial Interests, Institutional, Invited Speaker, GEM1801 clinical study: Incyte; Financial Interests, Institutional, Invited Speaker, GEM1801 clinical study: MSD; Financial Interests, Institutional, Invited Speaker, National coordinator of Spotlight 203 clinical trial: Highlight Therapeutics; Non-Financial Interests, Invited Speaker: Spanish Melanoma Group. A. Arance: Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Other, travel and accommodation: Pierre Fabre; Financial Interests, Personal, Research Grant: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Other, travel and accommodation: Novartis; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Other, travel and accommodation: Roche; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Other, travel and accommodation: BMS; Financial Interests, Personal, Research Grant: BMS; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Invited Speaker, travel and accommodation: MSD; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Invited Speaker: MERCK; Financial Interests, Personal, Advisory Role: MERCK; Financial Interests, Personal, Other, travel and accommodation: MERCK; Financial Interests, Personal, Research Grant: MERCK; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Other, travel and accommodation: Sanofi; Financial Interests, Personal, Research Grant: Sanofi; Financial Interests, Personal, Research Grant: Amgen. M.A. Berciano Guerrero: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Pharmamar; Financial Interests, Personal, Invited Speaker: Kyowa Kirin; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Pharmamar. M. Gonzalez Cao: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Apexigen; Financial Interests, Personal, Advisory Role: Pierre Fabre. J. Vidal: Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Guardant; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Roche. T. Puertolas Hernandez: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Invited Speaker: MSD. A. Soria: Financial Interests, Personal, Other, honoraria: Roche; Financial Interests, Personal, Other, honoraria: Merck Serono; Financial Interests, Personal, Other, honoraria: Novartis; Financial Interests, Personal, Other, honoraria: BMS; Financial Interests, Personal, Other, honoraria: Sanofi; Financial Interests, Personal, Other, honoraria: Pierre Fabre; Financial Interests, Personal, Other, honoraria: MSD; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Personal, Speaker’s Bureau: Pierre Fabre; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Other, travel accommodation: Novartis; Financial Interests, Personal, Other, travel accommodation: BMS; Financial Interests, Personal, Other, travel accommodation: Merck. C. Aguado de la Rosa: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Non-Financial Interests, Personal, Other, non-financial support: Roche; Financial Interests, Personal, Other, non-financial support: MSD; Financial Interests, Personal, Other, non-financial support: Pierre Fabre. P. Sánchez Mauriño: Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: BMS; Financial Interests, Personal, Other: Pierre Fabre; Financial Interests, Personal, Other: Sanofi; Financial Interests, Personal, Other: MSD; Financial Interests, Institutional, Other: Novartis; Financial Interests, Institutional, Other: BMS; Financial Interests, Institutional, Other: Pierre Fabre; Financial Interests, Institutional, Other: Sanofi; Financial Interests, Institutional, Other: MSD. P. Foro: Financial Interests, Personal, Invited Speaker: Jansen; Financial Interests, Personal, Invited Speaker: Astellas. A. Alvarez Gonzalez: Financial Interests, Personal, Advisory Role, Revisor Radiation Oncology study GEM1802: Pierre Fabre; Financial Interests, Personal, Principal Investigator, Trial MK-3475-867: MSD. A. Berrocal: Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Other, travel accommodation: BMS; Financial Interests, Personal, Other, honoraria: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Other, travel accommodation: MSD; Financial Interests, Personal, Other, honoraria: MSD; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Other, honoraria: Novartis; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Other, honoraria: Roche; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role, honoraria: Pierre Fabre; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Other, honoraria: Merck. All other authors have declared no conflicts of interest.
1039MO - CheckMate 204: 3-year outcomes of treatment with combination nivolumab (NIVO) plus ipilimumab (IPI) for patients (pts) with active melanoma brain metastases (MBM)
- Kim A. Margolin (Duarte, CA, United States of America)
Abstract
Background
In CheckMate 204, asymptomatic pts (cohort A) with active, untreated MBM achieved high intracranial (IC) and extracranial (EC) response rates with NIVO + IPI; efficacy was lower in pts with symptomatic and/or steroid-requiring MBM (cohort B). Here, we report 3-y response and survival outcomes in both cohorts, along with first results of the blinded independent central review (BICR) of imaging data.
Methods
In this open-label, multicenter, phase II study, pts with metastatic melanoma and ≥ 1 nonirradiated brain metastasis 0.5–3 cm in diameter received NIVO 1 mg/kg + IPI 3 mg/kg Q3W × 4, followed by NIVO 3 mg/kg Q2W until progression or unacceptable toxicity. The primary endpoint was IC clinical benefit rate, defined as the proportion of pts with complete response (CR), partial response (PR), or stable disease (SD) ≥ 6 mo (per modified RECIST 1.1). Investigator (INV)-assessed and BICR-assessed response and PFS were evaluated along with OS.
Results
At an overall minimum follow-up of 34 mo (median follow-up: 34 mo, cohort A; 7.5 mo, cohort B), there were 101 INV-assessed asymptomatic pts (95 BICR-evaluable) and 18 symptomatic pts (17 BICR-evaluable). INV- and BICR-response rates were consistent (table), with a concordance rate among evaluable pts of 85% for cohort A and 94% for cohort B. For cohort A, 36-mo IC progression-free survival (PFS) was 54% (95% CI, 43–64) by INV and 52% (41–62) by BICR, and overall survival (OS) was 72% (62–80). For cohort B, 36-mo IC PFS was 19% (95% CI, 5–40) by INV and 28% (10–50) by BICR, and OS was 37% (14–60). No new safety signals or treatment-related deaths were reported.
Conclusions
High concordance was observed between INV- and BICR-assessed responses in this trial for both cohorts. The durable 3-y OS and PFS rates for the asymptomatic cohort support the use of first-line NIVO + IPI. Symptomatic pts with MBM remain difficult to treat, but some can derive long-term benefit from NIVO + IPI. aTotal patients includes 6 asymptomatic pts and 1 symptomatic pt for whom BICR data were not available. CI, confidence interval; ORR, objective response rate.
INV BICR Asymptomatic, n (%) N = 101 N = 101a CR 33 (33) 16 (16) 17 (17) 26 (26) 14 (14) 11 (11) PR 21 (21) 33 (33) 35 (35) 24 (24) 36 (36) 38 (38) SD ≥ 6 mo 4 (4) 5 (5) 4 (4) 4 (4) 5 (5) 3 (3) ORR, n (%; 95% CI) 54 (54; 43–64) 49 (49; 38–59) 52 (51; 41–62) 50 (50; 39–60) 50 (50; 39–60) 49 (49; 38–59) Symptomatic, n (%) N = 18 N = 18a CR 3 (17) 1 (6) 1 (6) 3 (17) 2 (11) 2 (11) PR 0 3 (17) 3 (17) 1 (6) 2 (11) 2 (11) SD ≥ 6 mo 0 0 0 0 0 0 ORR, n (%; 95% CI) 3 (17; 4–41) 4 (22; 6–48) 4 (22; 6–48) 4 (22; 6–48) 4 (22; 6–48) 4 (22; 6–48)
Clinical trial identification
NCT02320058.
Editorial acknowledgement
Writing and editorial assistance were provided by Melissa Kirk, PhD, and Michele Salernitano of Ashfield MedComms, an Ashfield Health Company, funded by Bristol Myers Squibb Company.
Legal entity responsible for the study
Bristol-Myers Squibb.
Funding
Bristol-Myers Squibb.
Disclosure
H.A. Tawbi: Financial Interests, Personal and Institutional, Advisory Role, Consulting/Advisory Role, Research Funding: Novartis; Financial Interests, Personal and Institutional, Advisory Role, Consulting/Advisory Role, Research Funding: Bristol-Myers Squibb; Financial Interests, Personal and Institutional, Advisory Role, Consulting/Advisory Role, Research Funding: Genentech/Roche; Financial Interests, Personal, Advisory Role, Consulting/Advisory Role, Research Funding: Merck; Financial Interests, Personal, Advisory Role, Consulting/Advisory Role: Array BioPharma; Financial Interests, Institutional, Funding, Research Funding: GlaxoSmithKline; Financial Interests, Institutional, Funding, Research Funding: Celgene; Financial Interests, Personal, Advisory Role, Consulting honorarium: Eisai. P.A. Forsyth: Financial Interests, Personal and Institutional, Research Grant, 1R21 grant, NIH DT Study Section grant reviewer panel, honoraria: NIH/NCI; Financial Interests, Institutional, Research Grant, Grant/research support: CDMRP; Financial Interests, Institutional, Research Grant, Grant/research support: Department of Defense; Financial Interests, Institutional, Research Grant, Grant/research support: Pfizer; Financial Interests, Institutional, Research Grant, Grant/research support: State of Florida Bankhead Coley; Financial Interests, Institutional, Research Grant, Grant/research support: Moffitt Center of Excellence Celgene Project; Financial Interests, Personal, Other, Paid consultant: AbbVie, Inc. ; Financial Interests, Personal, Other, Paid consultant, honoraria : Ziopharm; Financial Interests, Personal, Other, Paid consultant: Novellus; Financial Interests, Personal, Other, Paid consultant: NCI Neuro-Oncology Branch Peer Review; Financial Interests, Personal, Other, Paid consultant : Physical Sciences Oncology Network; Financial Interests, Personal, Other, Paid consultant, honoraria : Tocagen; Financial Interests, Personal, Other, Honoraria, Membership on advisory Committee, review panel, board membership: BTG; Financial Interests, Personal, Other, Honoraria : NCRI; Financial Interests, Personal, Other, Membership on advisory Committee, review panel, board membership: Novocure ; Financial Interests, Personal, Other, Membership on advisory Committee, review panel, board membership : Inovio; Financial Interests, Personal, Invited Speaker, Membership on advisory Committee, review panel, board membership : Bayer. F..S. Hodi: Financial Interests, Personal and Institutional, Advisory Role, Grant to institution; consulting; Royalties to institution: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role, Consulting: Merck; Financial Interests, Personal, Advisory Role, Consulting: EMD Serono; Financial Interests, Personal and Institutional, Advisory Role, Consulting; grant to institution; royalties to institution: Novartis; Financial Interests, Personal, Advisory Role, Advisory Board: Surface; Financial Interests, Personal, Advisory Role, Advisory Board: Compass Therapeutics; Financial Interests, Personal, Advisory Role, Scientific Advisory Board; equity: Apricity; Financial Interests, Personal, Advisory Role, Advisor Consultant: Aduro; Financial Interests, Personal, Advisory Role, Consultant: Sanofi; Financial Interests, Personal, Advisory Role, Advisory Board; equity: Pionyr; Financial Interests, Personal, Advisory Role, Advisor: 7 Hills Pharma; Financial Interests, Personal, Other, Scientific Advisory Board; equity: Torque; Financial Interests, Personal, Advisory Board, Advisory Board: Rheos; Financial Interests, Personal, Advisory Role, Consultant: Kairos; Financial Interests, Personal, Advisory Role, Scientific Advisory Board; equity: Bicara; Financial Interests, Personal, Advisory Role, Consultant: Psioxus Therapeutics; Financial Interests, Personal, Advisory Role, Consultant: Pieris Pharmacutical; Financial Interests, Personal, Advisory Board, Advisory Board: Zumutor; Financial Interests, Personal, Advisory Role, Consultant: Corner Therapeutics; Financial Interests, Personal, Advisory Role, Consultant: Eisai; Financial Interests, Personal, Advisory Board, Scientific Advisory Board: Checkpoint Therapeutics; Financial Interests, Personal, Advisory Role, Consultant: Idera; Financial Interests, Personal, Advisory Role, Consultant: Takeda; Financial Interests, Personal, Advisory Role, Consultant: Genentech/Roche; Financial Interests, Personal, Advisory Board, Advisory Board: Bioentre; Financial Interests, Personal, Advisory Role, Consultant: Gossamer. A. Algazi: Financial Interests, Personal and Institutional, Other, Advisor fees, stock options, travel support, clinical trial support paid to UCSF: OncoSec Medical, Inc.; Financial Interests, Personal, Stocks/Shares, Stock options: Valitor Biosciences; Financial Interests, Personal and Institutional, Research Grant, Advisory Board Member Honoraria, Clinical trial support paid to UCSF: Regeneron; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Acerta; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Amgen; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: AstraZeneca; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Dynavax; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Genentech; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Idera; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Incyte; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: ISA; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: LOXO; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Merck; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Novartis; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Sensei; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Tessa; Financial Interests, Personal, Funding, Advisory Board Member Honoraria: Array. O. Hamid: Financial Interests, Personal and Institutional, Advisory Role, Consulting : Bristol Myers Squibb; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Aduro; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Akeso; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Amgen; Financial Interests, Personal, Advisory Role, Consulting: Beigene; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Bioatla; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Genentech; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: GlaxoSmithKline; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Immunocore; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Idera; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Incyte; Financial Interests, Personal, Advisory Role, Consulting: Janssen; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Merck; Financial Interests, Personal and Institutional, Speaker’s Bureau, Consulting, Contracted Research for Institution: NextCure; Financial Interests, Personal and Institutional, Speaker’s Bureau, Consulting, Speaker, Contracted Research for Institution: Novartis; Financial Interests, Personal and Institutional, Speaker’s Bureau, Consulting, Speaker, Contracted Research for Institution: Pfizer; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Speaker, Contracted Research for Institution: Sanofi Regeneron; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Seattle Genetics; Financial Interests, Personal, Advisory Role, Consulting: Tempus; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Zelluna; Financial Interests, Institutional, Research Grant, Contracted Research for Institution: Arcus; Financial Interests, Institutional, Research Grant, Contracted Research for Institution: CytomX; Financial Interests, Institutional, Research Grant, Contracted Research for Institution: Exelixis; Financial Interests, Institutional, Research Grant, Contracted Research for Institution: Iovance; Financial Interests, Institutional, Research Grant, Contracted Research for Institution: Moderna; Financial Interests, Institutional, Research Grant, Contracted Research for Institution: Merck Serono. C.D. Lao: Financial Interests, Institutional, Other, Research support, travel, medical ad board: Bristol Myers Squibb; Financial Interests, Institutional, Other, Research support: Dynavax; Financial Interests, Institutional, Other, Travel, Medical ad board: Immunocore; Financial Interests, Institutional, Other, Research support: GlaxoSmithKline; Financial Interests, Institutional, Other, Research support: Merck. M.B. Atkins: Financial Interests, Personal and Institutional, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Genentech-Roche; Financial Interests, Personal, Advisory Board: Werewolf; Financial Interests, Personal, Advisory Board: Pyxis Oncology; Financial Interests, Personal, Other, Consultant: AstraZeneca; Financial Interests, Personal, Advisory Board: PACT; Financial Interests, Personal, Other, Consultant: Idera; Financial Interests, Personal, Other, Consultant: Agenus; Financial Interests, Personal, Advisory Board: Elpis; Financial Interests, Personal, Other, Consultant: Adagene; Financial Interests, Personal, Other, Consultant: Exelixis; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Apexigen; Financial Interests, Personal, Other, Consultant: Neoleukin; Financial Interests, Personal, Other, Consultant: Iovance; Financial Interests, Personal, Other, Consultant: Immunocore; Financial Interests, Personal, Other, Consultant: Calithera; Financial Interests, Personal, Advisory Board: Aveo; Financial Interests, Personal, Advisory Board: Leads Biopharma. K. Lewis: Financial Interests, Institutional, Funding: Bristol-Myers Squibb. M.A. Postow: Financial Interests, Personal and Institutional, Other, Consulting/Advisory Role, Honoraria, Research Funding: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Other, Consulting/Advisory Role, Honoraria, Research Funding: Merck; Financial Interests, Personal, Other, Consulting/Advisory Role: Eisai; Financial Interests, Personal and Institutional, Other, Consulting/Advisory Role, Research Funding: Novartis; Financial Interests, Personal and Institutional, Funding, Research Funding: Array BioPharma; Financial Interests, Personal, Other, Consulting/Advisory Role: Incyte; Financial Interests, Personal, Other, Consulting/Advisory Role: NewLink Genetics; Financial Interests, Personal, Other, Consulting/Advisory Role: Aduro; Financial Interests, Institutional, Funding, Research Funding: RGenix; Financial Interests, Institutional, Funding, Research Funding: Infinity; Financial Interests, Institutional, Funding, Research Funding: AstraZeneca. N.I. Khushalani: Financial Interests, Personal, Advisory Role, Consulting/Advisory Role: Array BioPharma; Financial Interests, Personal, Advisory Role, Consulting/Advisory Role, Honoraria, Research Funding: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Consulting/Advisory Role: EMD Serono; Financial Interests, Personal, Advisory Role, Consulting/Advisory Role: Genentech; Financial Interests, Personal and Institutional, Other, Consulting/Advisory Role, Research Funding: HUYA Bioscience International; Financial Interests, Personal and Institutional, Other, Consulting/Advisory Role, Research Funding: Regeneron; Financial Interests, Personal, Other, Consulting/Advisory Role: Immunocore; Financial Interests, Personal and Institutional, Other, Consulting/Advisory Role, Research Funding: Merck; Financial Interests, Personal, Other, Honoraria: Sanofi; Financial Interests, Institutional, Funding, Research Funding: Amgen; Financial Interests, Institutional, Funding, Research Funding: Celgene; Financial Interests, Institutional, Funding, Research Funding: GlaxoSmithKline; Financial Interests, Institutional, Funding, Research Funding: Novartis; Financial Interests, Personal, Stocks/Shares, Stock/Other Ownership Interests: Amarin Corporation; Financial Interests, Personal, Stocks/Shares, Stock/Other Ownership Interests: Bellicum Pharmaceuticals; Financial Interests, Personal, Stocks/Shares, Stock/Other Ownership Interests: Mazor Robotics; Financial Interests, Personal, Stocks/Shares, Stock/Other Ownership Interests: TransEnterix; Financial Interests, Personal, Advisory Role: Jounce. A.C. Pavlick: Financial Interests, Personal and Institutional, Advisory Role, Consulting/Advisory Role, Research Funding: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Advisory Role, Consulting/Advisory Role, Research Funding: Merck; Financial Interests, Personal and Institutional, Advisory Role, Consulting/Advisory Role, Travel, Accommodations, and Expenses, Research Funding: Regeneron; Financial Interests, Personal, Advisory Role, Consulting/Advisory Role, Travel, Accommodations, and Expenses: Sanofi/Regeneron; Financial Interests, Personal, Advisory Role, Consulting/Advisory Role, Travel, Accommodations, and Expenses: Array BioPharma; Financial Interests, Institutional, Funding, Research Funding: Celldex; Financial Interests, Institutional, Funding, Research Funding: Millennium. D.A. Reardon: Financial Interests, Institutional, Other, Research paid to DFCI: Acerta Phamaceuticals; Financial Interests, Institutional, Other, Research paid to DFCI, Advisory/Consultation: Agenus; Financial Interests, Institutional, Other, Research paid to DFCI, Advisory/Consultation: Celldex; Financial Interests, Institutional, Other, Research paid to DFCI, Advisory/consultation: EMD Serono; Financial Interests, Institutional, Other, Research paid to DFCI: Incyte; Financial Interests, Institutional, Other, Research paid to DFCI, Advisory/consultation: Inovio; Financial Interests, Institutional, Other, Research paid to DFCI: Midatech; Financial Interests, Institutional, Other, Research paid to DFCI: Omniox; Financial Interests, Institutional, Other, Research paid to DFCI: Tragara; Financial Interests, Personal, Other, Advisory/consultation: AbbVie; Financial Interests, Personal, Other, Advisory/consultation: Advantagene; Financial Interests, Personal, Other, Advisory/consultation: Amgen; Financial Interests, Personal, Other, Advisory/consultation: Bayer; Financial Interests, Personal, Other, Advisory/consultation: Bristol Myers Squibb; Financial Interests, Personal, Other, Advisory/consultation: DelMar; Financial Interests, Personal, Other, Advisory/consultation: Genentech/Roche; Financial Interests, Personal, Other, Advisory/consultation: Merck; Financial Interests, Personal, Other, Advisory/consultation: Merck KGaA; Financial Interests, Personal, Other, Advisory/consultation: Monteris; Financial Interests, Personal, Other, Advisory/consultation: Novocure; Financial Interests, Personal, Other, Advisory/consultation: Oncorus; Financial Interests, Personal, Other, Advisory/consultation: Oxigene; Financial Interests, Personal, Other, Advisory/consultation: Regeneron; Financial Interests, Personal, Other, Advisory/consultation: Stemline; Financial Interests, Personal, Other, Advisory/consultation: Taiho Oncology, Inc.; Financial Interests, Personal, Other, Advisory/consultation: Boston Biomedical; Financial Interests, Personal, Other, Advisory/consultation: Medicenna. C. Lee: Financial Interests, Personal, Stocks/Shares, Employment: Bristol Myers Squibb. T. Bas: Financial Interests, Personal, Stocks/Shares, Employment, Stock Ownership: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Consulting/advisory role - immediate family member family member: Fiore Healthcare Advisors. All other authors have declared no conflicts of interest.
Discussion 1038MO and 1039MO
- Teresa Petrella (Toronto, Ontario, Canada)
LBA39 - Personalized combination of neoadjuvant domatinostat, nivolumab (NIVO) and ipilimumab (IPI) in stage IIIB-D melanoma patients (pts) stratified according to the interferon-gamma signature (IFN-γ sign): The DONIMI study
- Christian U. Blank (Amsterdam, Netherlands)
Abstract
Background
Neoadjuvant (neoadj) IPI + NIVO induces high pathologic response rates (pRR 72-78%) in stage IIIB-D melanoma which is strongly associated with long-term relapse-free survival (RFS). Pts with a low baseline IFN-γ sign are less likely to respond. The class I histone deacetylase inhibitor domatinostat (DOM) increased intratumoral T cell infiltration and IFN-γ sign expression in melanoma. DONIMI tests neoadj combinations of NIVO ± IPI with DOM stratified according to IFN-γ sign from tumor biopsies.
Methods
This phase 1b study tested the safety/feasibility of neoadj NIVO ± DOM ± IPI in stage III RECISTv1.1 measurable melanoma. It also prospectively tested the IFN-γ sign for the first time, randomizing IFN-γ sign high pts to arm A (2 cycles NIVO 240mg q3w) or arm B (2 cycles NIVO 240mg + DOM 200mg BID, d1-14, q3w), and IFN-γ sign low pts to arm C (same treatment regimen as arm B) or arm D (2 cycles NIVO 240mg + IPI 80mg + DOM 200mg QD, d1-14, q3w). Surgery was planned after 6 wks. Adjuvant NIVO 480mg q4w or dabrafenib + trametinib (non-responding BRAFV600 mutated pts) started at week 12 for 52 wks.
Results
Between Jan 2020 - Apr 2021, 40 pts were enrolled (10 pts in each arm). Baseline characteristics were comparable. All treatment regimens were feasible as surgery was performed on time in all pts (wk 6 ± 1 wk). Gr 3-4 systemic treatment-related AEs (trAEs) during the first 12 wks occurred in 0% in arm A, 20% in arm B, 40% in arm C and 20% in arm D. Except for gr 2-3 DOM-related rash, no unexpected trAEs were observed. pRR was 90% in arm A, 80% in arm B (both IFN-γ sign high pts), 30% in arm C and 40% in arm D (both IFN-γ sign low pts). 2 pts in arm D developed distant metastases before surgery. At data cutoff (Jul 7, median FU 8.9 months), estimated 6-month RFS rate was 100% in IFN-γ sign high pts and 79.4% in IFN-γ sign low pts.
Conclusions
Neoadj NIVO ± DOM ± IPI appears safe and feasible. DONIMI shows prospectively the discriminative ability of the IFN-γ sign algorithm. It adequately identified pts who can benefit from NIVO ± DOM alone (IFN-γ high pts) vs pts who might need an alternative scheme (IFN-γ low pts). Standard DOM dosing (200mg BID d1-14) plus IPI + NIVO is currently being tested.
Clinical trial identification
NCT04133948.
Legal entity responsible for the study
Netherlands Cancer Institute (PI: Christian Blank).
Funding
4SC.
Disclosure
C.U. Blank: Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: GSK; Financial Interests, Institutional, Advisory Board: AstraZenica; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Institutional, Advisory Board: Genmab; Financial Interests, Institutional, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Third Rock Ventures; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Nanostring; Financial Interests, Institutional, Research Grant: 4SC; Financial Interests, Personal, Ownership Interest: Immagene BV. A.M. Menzies: Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Advisory Board: Pierre-Fabre; Financial Interests, Institutional, Advisory Board: QBiotics. R.P.M. Saw: Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: QBiotics; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: Novartis. A.J. Spillane: Non-Financial Interests, Institutional, Advisory Board: QBiotics; Financial Interests, Personal, Other, fees for professional services: Stryker. B.A. van de Wiel: Non-Financial Interests, Institutional, Advisory Board: BMS. R.A. Scolyer: Financial Interests, Institutional, Other, professional services: QBiotics; Financial Interests, Institutional, Other, professional services: Novartis; Financial Interests, Institutional, Other, professional services: MSD; Financial Interests, Institutional, Other, professional services: NeraCare; Financial Interests, Institutional, Other, professional services: Amgen Inc; Financial Interests, Institutional, Other, professional services: BMS; Financial Interests, Institutional, Other, professional services: Myriad Genetics; Financial Interests, Institutional, Other, professional services: GSK. A.C.J. van Akkooi: Financial Interests, Institutional, Advisory Board: Amgen; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Merck-Pfizer; Financial Interests, Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Advisory Board: Sirius Medical; Financial Interests, Institutional, Advisory Board: 4SC; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Merck-Pfizer. G.V. Long: Financial Interests, Institutional, Advisory Board: Aduro Biotech Inc; Financial Interests, Institutional, Advisory Board: Amgen Inc; Financial Interests, Institutional, Advisory Board: Array Biopharma Inc; Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim International GmbH; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: Highlight Therapeutics S.L.; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Novartis Pharma AG; Financial Interests, Institutional, Advisory Board: Pierre-Fabre; Financial Interests, Institutional, Advisory Board: QBiotics Group Limited; Financial Interests, Institutional, Advisory Board: Regeneron Pharmaceuticals Inc. All other authors have declared no conflicts of interest.
LBA40 - SECOMBIT: The best sequential approach with combo immunotherapy [ipilimumab (I) /nivolumab (N)] and combo target therapy [encorafenib (E)/binimetinib (B)] in patients with BRAF mutated metastatic melanoma: A phase II randomized study
- Paolo A. Ascierto (Napoli, Italy)
Abstract
Background
Treatment with targeted therapy (BRAF and MEK inhibitors) and immune-checkpoint inhibitors (anti-CTLA4, anti-PD-1) have improved the outcome of
Methods
From Nov 2016 to May 2019, 37 sites in 9 countries enrolled 251 patients with untreated, metastatic
Results
The study primary endpoint was met in each arm with at least 30 patients alive at 24 months. The median follow-up estimated with the reverse Kaplan-Meier method was 32.2 months (IQR= 27.9-41.6). The median OS was not reached in any of the treatment arms. The survival rate at 2 and 3 years was 65% and 54% in arm A, 73% and 62% in arm B and 69% and 60% in arm C respectively. Total PFS rate at 2 and 3 years was 46% and 41% in arm A, 65% and 53% in arm B, 57% and 54% in arm C.
Conclusions
The OS and TPFS rates at 2 and 3 years showed a better trend in arm B and C. Data continue to be collected to provide additional information on the long-term benefit of the three treatment combinations. The biomarkers analysis is ongoing.
Clinical trial identification
NCT02631447.
Legal entity responsible for the study
Fondazione Melanoma Onlus.
Funding
BMS and Array Biopharma/Pfizer.
Disclosure
P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS; Financial Interests, Personal, Other, Consultant and Advisory Role: Roche Genentech; Financial Interests, Personal, Other, Consultant and Advisory Role: MSD; Financial Interests, Personal, Other, Consultant and Advisory Role: Novartis; Financial Interests, Personal, Other, Consultant and Advisory Role: Array; Financial Interests, Personal, Other, Consultant and Advisory Role: Merck Serono; Financial Interests, Personal, Other, Consultant and Advisory Role: Pierre Fabre; Financial Interests, Personal, Other, Consultant and Advisory Role: Incyte; Financial Interests, Personal, Other, Consultant and Advisory Role: Genmab; Financial Interests, Personal, Other, Consultant and Advisory Role: Medimmune; Financial Interests, Personal, Other, Consultant and Advisory Role: AstraZeneca; Financial Interests, Personal, Other, Consultant and Advisory Role: Sindax; Financial Interests, Personal, Other, Consultant and Advisory Role: Sun Pharma; Financial Interests, Personal, Other, Consultant and Advisory Role: Sanofi; Financial Interests, Personal, Other, Consultant and Advisory Role: Idera; Financial Interests, Personal, Other, Consultant and Advisory Role: Ultimovacs; Financial Interests, Personal, Other, Consultant and Advisory Role: Sandoz; Financial Interests, Personal, Other, Consultant and Advisory Role: Immunocore; Financial Interests, Personal, Other, Consultant and Advisory Role: 4SC; Financial Interests, Personal, Other, Consultant and Advisory Role: Alkermes; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Consultant and Advisory Role: Nektar; Financial Interests, Personal, Other, Consultant and Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Other, Advisory Role: Eisai; Financial Interests, Personal, Other, Consultant and Advisory Role: Regeneron; Financial Interests, Personal, Other, Consultant Role: Daiichi Sankyo; Financial Interests, Personal, Other, Consultant Role: Pfizer; Financial Interests, Personal, Other, Consultant Role: Oncosec; Financial Interests, Personal, Other, Consultant Role: Nouscom; Financial Interests, Personal, Other, Consultant Role: Takis; Financial Interests, Personal, Other, Consultant Role: Lunaphore; Financial Interests, Personal, Other, Advisory Role: Seagen; Financial Interests, Institutional, Funding, Clinical trial and translational research: BMS; Financial Interests, Institutional, Funding, Clinical Trial: Roche-Genentech; Financial Interests, Institutional, Funding, Clinical Trial: Array; Financial Interests, Institutional, Funding, Clinical Trial: Sanofi; Non-Financial Interests, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Other, Member of Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Invited Speaker, November 2017 - December 2020: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member: SITC; Non-Financial Interests, Member: EORTC Melanoma Cooperative Group; Non-Financial Interests, Member: AIOM; Non-Financial Interests, Member: SMR; Other, Travel Support: MSD. M. Mandala: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Novartis. P.F. Ferrucci: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Pierre Fabre. P. Rutkowski: Financial Interests, Personal, Advisory Role: Blueprint Medicines; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Research Grant: Pfizer; Non-Financial Interests, Officer: ASCO; Non-Financial Interests, Member: Polish Society of Surgical Oncology. M. Guidoboni: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Institutional, Research Grant: MSD. A.M. Arance Fernandez: Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Other, Travel expenses: Pierre Fabre; Financial Interests, Institutional, Research Grant: Pierre Fabre; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Other, Travel expenses: Novartis; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Other, Travel expenses: Roche; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Other, Travel expenses: BMS; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Other, Travel expenses: MSD; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Personal, Advisory Role: Merck-Serono; Financial Interests, Personal, Invited Speaker: Merck-Serono; Financial Interests, Personal, Other, Travel expenses: Merck-Serono; Financial Interests, Institutional, Research Grant: Merck-Serono; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Other, Travel expenses: Sanofi; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Amgen. V. Ferraresi: Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Other, Travel accomodation: BMS; Financial Interests, Personal, Other, Travel accomodation: Pierre Fabre; Financial Interests, Personal, Other, Travel accomodation: MSD. E. Maiello: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, Travel expenses: AstraZeneca; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Other, Travel expenses: Sanofi; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Other, Travel expenses: Servier; Financial Interests, Personal, Invited Speaker: Merck-Serono; Financial Interests, Personal, Advisory Board: Merck- Serono; Financial Interests, Personal, Other, Travel expenses: Merck-Serono; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Other, Travel expenses: Lilly; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Other, Travel expenses: Eisai; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Other, Travel expenses: Roche; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Funding: MSD. M. Guida: Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pierre Fabre. M. Del Vecchio: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: Sanofi. M.T. Fierro: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: AbbVie; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Other, Travel expenses: Novartis; Financial Interests, Personal, Other, Travel expenses: BMS; Financial Interests, Personal, Other, Travel expenses: MSD; Financial Interests, Personal, Other, Travel expenses: Pierre Fabre; Financial Interests, Personal, Other, Travel expenses: AbbVie; Financial Interests, Personal, Other, Travel expenses: Lilly. P. Queirolo: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Merck-Serono; Financial Interests, Personal, Advisory Role: Sun Pharma; Financial Interests, Personal, Advisory Role: Sanofi. C. Lebbe: Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: BMS; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Pierre Fabre; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Incyte; Financial Interests, Personal, Other, Travel expenses: BMS; Financial Interests, Personal, Other, Travel expenses: MSD; Financial Interests, Personal, Other, Travel expenses: Novartis; Financial Interests, Personal, Other, Travel expenses: Sanofi; Financial Interests, Personal, Other, Travel expenses: Pierre Fabre; Financial Interests, Personal, Other: Avantis Medical System. I. Melero: Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Alligator; Financial Interests, Institutional, Research Grant: Pharmamar; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Genmab; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Alligator; Financial Interests, Personal, Advisory Role: Pharmamar; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Genmab; Financial Interests, Personal, Advisory Role: Merck-Serono; Financial Interests, Personal, Advisory Role: Numab; Financial Interests, Personal, Advisory Role: Gossamer; Financial Interests, Personal, Advisory Role: Bioncotech. G. Palmieri: Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Incyte; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: Roche-Genentech. A.M. Grimaldi: Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Roche-Genentech; Financial Interests, Personal, Invited Speaker: Merck-Serono; Financial Interests, Personal, Other, Travel grant: BMS; Financial Interests, Personal, Other, Travel grant: MSD; Financial Interests, Personal, Other, Travel grant: Merck- Serono. R. Dummer: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Catalaym; Financial Interests, Personal, Invited Speaker: MaxiVAX SA; Financial Interests, Personal, Invited Speaker: Amgend Takeda; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Sun Pharma; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Second Genome; Financial Interests, Personal, Invited Speaker: Regeneron; Financial Interests, Personal, Invited Speaker: Alligator; Financial Interests, Personal, Invited Speaker: T3Pharma. V. Chiarion Sileni: Financial Interests, Personal, Advisory Role: Merck-Serono; Financial Interests, Personal, Invited Speaker: Merck-Serono; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Other, Travel expenses: Pierre Fabre; Financial Interests, Personal, Other, Travel expenses: BMS; Financial Interests, Personal, Advisory Role: Pierre Fabre. All other authors have declared no conflicts of interest.
1041MO - 5-year update on COLUMBUS: A randomized phase III trial of encorafenib (enco) + binimetinib (bini) versus enco or vemurafenib (vem) in patients (pts) with BRAF V600-mutant melanoma
- Reinhard Dummer (Zurich, Switzerland)
Abstract
Background
Combined BRAF/MEK inhibitor therapy has demonstrated benefits on progression-free survival (PFS) and overall survival (OS) and is standard of care for the treatment (tx) of advanced
Methods
In COLUMBUS Part 1, 577 pts with advanced/metastatic
Results
In the enco + bini arm, the 5-year OS rate (95% CI) in all pts (n=192), those with lactate dehydrogenase (LDH) ≤ upper limit of normal (ULN) at baseline (n=137), and low tumor burden (n=88) was 35% (28–42), 45% (36–53), and 48% (37–58), respectively (data cut-off: Sep 15, 2020). Other efficacy results are shown in the table. Safety results were consistent with the known tolerability profile of enco + bini. Adverse events (AEs) occurring in ≥ 20% of enco + bini pts were nausea, diarrhea, vomiting, arthralgia, fatigue, increased blood creatinine phosphokinase (CPK), headaches, constipation, asthenia, and pyrexia. Grade 3/4 AEs occurring in ≥ 2.5% of pts in the enco + bini were hypertension, pyrexia, abdominal pain, diarrhea, and vomiting. Grade 3/4 abnormal laboratory values occurring in ≥ 2.5% pts in the enco + bini arm were increased gamma-glutamyl transferase, increased blood CPK, anemia, increased alanine transaminase, and hyperglycemia. 12%–14% of pts in each arm discontinued tx due to AEs. The most common anti-cancer tx after enco + bini were checkpoint inhibitors. Additional analyses will be presented. *% (95% CI) †n (%)
Enco + bini (n=192) Enco (n=194) Vem (n=191) 5-year PFS rate* 23 (16–30) 19 (13–27) 10 (5–18) 5-year OS rate* LDH ≤ ULN n LDH > ULN n Low tumor burden n 35 (28–42) 45 (36–53) 137 9 (3–18) 55 48 (37–58) 88 35 (28–42) 42 (33–50) 147 14 (6–26) 47 50 (39–60) 94 21 (16–28) 28 (21–36) 139 4 (1–12) 52 38 (28–49) 84 Objective response rate* 64 (57–71) 52 (44–59) 41 (34–48) Disease control rate* 92 (87–96) 84 (78–89) 81 (75–86) Complete response† 27 (14) 15 (8) 16 (8) Partial response† 96 (50) 85 (44) 62 (32) Stable disease† (includes non-complete response or non-progressive disease) 54 (28) 63 (32) 77 (40) Progressive disease† (includes best response of unknown or no assessment) 15 (8) 31 (16) 36 (19)
Conclusions
Updated results with enco + bini indicate continued long-term benefit in pts with advanced/metastatic
Clinical trial identification
NCT01909453; release date: July 26, 2013.
Editorial acknowledgement
Editorial and medical writing support was provided by Raya Mahbuba at Caudex and was funded by Pfizer.
Legal entity responsible for the study
Pfizer.
Funding
Array BioPharma, which was acquired by Pfizer in July 2019.
Disclosure
R. Dummer: Financial Interests, Personal, Advisory Board: Novartis, MSD, BMS, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, T3 Pharma, MaxiVAX SA, touchIME. K.T. Flaherty: Financial Interests, Personal, Member of the Board of Directors: Clovis Oncology, Strata Oncology, Vivid Biosciences, Checkmate Pharmaceuticals; Financial Interests, Personal, Advisory Board: X4 Pharmaceuticals, PIC Therapeutics, Sanofi, Amgen, Asana, Adaptimmune, Fount, Aeglea, Shattuck Labs, Tolero, Apricity, Oncoceutics, Fog Pharma, Neon, Tvardi, xCures, Monopteros, Vibliome; Financial Interests, Personal, Other: Lilly, Novartis, Genentech, BMS, Merck, Takeda, Verastem, Boston Biomedical, Pierre Fabre, Debiopharm; Financial Interests, Personal and Institutional, Funding: Novartis, Sanofi. C. Robert: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca. A. Arance: Financial Interests, Personal, Other, Consultant, Travel, Accommodations, Expenses: Pierre Fabre; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Funding: Pierre Fabre; Financial Interests, Personal, Other, Consultant, Travel, Accommodations, Expenses: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Funding: Novartis; Financial Interests, Personal, Other, Consultant, Travel, Accommodations, Expenses: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Funding: Roche; Financial Interests, Personal, Other, Consultant, Travel, Accommodations, Expenses: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Funding: Bristol Myers Squibb; Financial Interests, Personal, Other, Consultant, Travel, Accommodations, Expenses: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Funding: MSD; Financial Interests, Personal, Other, Consultant, Travel, Accommodations, Expenses: Merck; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Funding: Merck; Financial Interests, Personal, Other, Consultant, Travel, Accommodations, Expenses: Sanofi; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Funding: Sanofi; Financial Interests, Personal, Funding: Amgen. J.W.B. de Groot: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Servier. C. Garbe: Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal and Institutional, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal and Institutional, Advisory Board: Neracare; Financial Interests, Personal and Institutional, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Philogen; Financial Interests, Personal and Institutional, Advisory Board: Roche; Financial Interests, Personal and Institutional, Advisory Board: Sanofi. H.J. Gogas: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Non-Financial Interests, Personal, Member, Steering committee: Amgen; Financial Interests, Institutional, Other, Local PI: Amgen; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Institutional, Other, Local PI: Bristol Myers Squibb; Financial Interests, Institutional, Other, Local PI: MSD; Financial Interests, Institutional, Research Grant: Pfizer. R. Gutzmer: Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, Novartis, Amgen, Merck Serono, Almirall Hermal, SUN, Sanofi, Pierre-Fabre; Financial Interests, Institutional, Other, Clinical study fees: Roche, BMS, MSD, Novartis, Amgen, Merck Serono, SUN, Sanofi, Pierre-Fabre, Philogen, Pfizer; Financial Interests, Personal, Advisory Board: BMS, Roche, Novartis, Almirall Hermal, MSD, Amgen, SUN, Sanofi, Pierre-Fabre, 4SC, Bayer, MerckSerono, Pfizer; Financial Interests, Institutional, Research Grant: Novartis, Pfizer, Johnson & Johnson, Amgen, Merck-Serono, SUN Pharma, Sanofi; Non-Financial Interests, Personal, Other, Travel/meeting support: Roche, BMS, SUN, Merck-Serono, Pierre-Fabre. G. Liszkay: Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Principal Investigator: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Principal Investigator: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Principal Investigator: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Principal Investigator: Pfizer; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Principal Investigator: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Principal Investigator: Incyte Corporation. C. Loquai: Financial Interests, Personal, Advisory Board: MSD, BMS, Merck, Novartis, Roche, Pierre Fabre, Sanofi, Sun Pharma, Biontech, Almiral Hermal; Financial Interests, Personal, Speaker’s Bureau: MSD, BMS, Merck, Novartis, Roche, Pierre Fabre, Sanofi, Sun Pharma; Financial Interests, Personal, Other, Travel reimbursement: MSD, BMS, Merck, Novartis, Roche, Pierre Fabre, Sanofi, Sun Pharma, Biontech, Almiral Hermal, Kyowa Kirin . M. Mandala: Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Advisory Board: Pierre Fabre; Financial Interests, Institutional, Invited Speaker: Pierre Fabre; Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Invited Speaker: Sanofi. D. Schadendorf: Financial Interests, Personal, Advisory Board: 4SC; Financial Interests, Personal, Advisory Board: Array Biopharma; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Immunocore; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: NEKTAR; Financial Interests, Personal, Advisory Board: Neracare; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Philogen; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Sandoz; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Board: Sanofi/Regeneron; Financial Interests, Personal, Member, Steering Committee Member: 4SC; Financial Interests, Institutional, Principal Investigator, Coordinating PI: 4SC; Financial Interests, Institutional, Research Grant: Array/Pfizer; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Member, Steering Committee Member: Bristol Myers Squibb; Financial Interests, Personal, Member, Steering Committee Member: MSD; Financial Interests, Institutional, Principal Investigator, Coordinating PI: MSD; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Personal, Member, Steering Committee Member: Nektar; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Nektar; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Member, Steering Committee Member: Novartis; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Novartis; Financial Interests, Institutional, Principal Investigator, Local PI: Philogen; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Pierre Fabre; Financial Interests, Institutional, Principal Investigator, Local PI: Roche; Financial Interests, Institutional, Principal Investigator, Local PI: Sanofi; Non-Financial Interests, Personal, Member, Board of Directors: EORTC-MG. N. Yamazaki: Financial Interests, Personal and Institutional, Speaker’s Bureau: Ono; Financial Interests, Personal and Institutional, Research Grant: Ono. F. Zohren: Financial Interests, Personal, Full or part-time Employment: Pfizer. M. Edwards: Financial Interests, Institutional, Full or part-time Employment, Salary paid by Pfizer: Pfizer. P.A. Ascierto: Financial Interests, Personal and Institutional, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Advisory Board: Roche-Genentech; Financial Interests, Personal and Institutional, Research Grant: Roche-Genentech; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal and Institutional, Advisory Board: Array; Financial Interests, Personal and Institutional, Research Grant: Array; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Pierre-Fabre; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Medimmune; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Syndax; Financial Interests, Personal, Advisory Board: Sun Pharma; Financial Interests, Personal and Institutional, Advisory Board: Sanofi; Financial Interests, Personal and Institutional, Research Grant: Sanofi; Financial Interests, Personal, Advisory Board: Idera; Financial Interests, Personal, Advisory Board: Ultimovacs; Financial Interests, Personal, Advisory Board: Sandoz; Financial Interests, Personal, Advisory Board: Immunocore; Financial Interests, Personal, Advisory Board: 4SC; Financial Interests, Personal, Advisory Board: Alkermes; Financial Interests, Personal, Advisory Board: Italfarmaco; Financial Interests, Personal, Advisory Board: Nektar; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Oncosec; Financial Interests, Personal, Advisory Board: Nouscom; Non-Financial Interests, Institutional, Principal Investigator: Takis; Financial Interests, Personal, Advisory Board: Lunaphore; Financial Interests, Personal, Advisory Board: Seagen. All other authors have declared no conflicts of interest.
Discussion LBA39, LBA40 and 1041MO
- Teresa Troiani (Napoli, Italy)