Displaying One Session

Barcelona Auditorium (Hall 2) Proffered Paper session
Date
28.09.2019
Time
08:30 - 10:00
Location
Barcelona Auditorium (Hall 2)
Chairs
  • Laurence Albiges (Villejuif, CEDEX, France)
  • Ignacio Duran Martinez (Santander, Spain)
Proffered Paper 1 – Genitourinary tumours, non-prostate Proffered Paper session

LBA54 - ENTRATA: Randomized, double-blind, phase II study of telaglenastat (tela; CB-839) + everolimus (E) vs placebo (pbo) + E in patients (pts) with advanced/metastatic renal cell carcinoma (mRCC) (ID 811)

Presentation Number
LBA54
Lecture Time
08:30 - 08:45
Speakers
  • Chung-Han Lee (New York, United States of America)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:30 - 10:00

Abstract

Background

Altered glucose and glutamine (gln) metabolism is a hallmark of RCC. Glutaminase (GLS) is a key enzyme in gln metabolism and drives proliferation of RCC cells when overexpressed. Tela, a novel, first-in-clinic, selective GLS inhibitor, blocks critical gln-dependent pathways and synergizes preclinically with signal transduction inhibitors (eg, E). In a phase I study in mRCC, telaE was well tolerated and had encouraging clinical activity. We present here results of a randomized phase II study of telaE vs pboE in 3L+ mRCC (NCT03163667).

Methods

Eligible pts had ≥2 prior lines of systemic therapy for mRCC, including ≥1 VEGFR-targeted tyrosine kinase inhibitor (TKI), KPS ≥70%, and measurable disease (RECIST 1.1). Pts were stratified by prior lines of TKI and MSKCC risk and randomized 2:1 to receive tela (800 mg PO BID) or pbo, plus E (10 mg PO QD), until disease progression/unacceptable toxicity. Primary endpoint is investigator-assessed progression-free survival (PFS) (RECIST 1.1; 1-sided alpha <0.2).

Results

69 pts were randomized (Table). Median PFS was 3.8 mo for telaE vs 1.9 mo for pboE (HR = 0.64 [95% CI, 0.34-1.20], 1-sided P = 0.079).Gr ≥3 adverse events (AEs) occurred in 80% telaE pts vs 60% pboE; most common were anemia (17% vs 17%), pneumonia (7% vs 4%), abdominal pain (7% vs 0%), thrombocytopenia (7% vs 0%), fatigue (4% vs 9%). Discontinuation rates due to AEs were similar (28% telaE, 30% pboE). There were no treatment-related deaths. Subgroup analyses were consistent w/ primary analysis. Survival data will be presented.

LBA54

Baseline Characteristics
TelaE n = 46PboE n = 23
Median age, y (range)65 (47-85)65 (37-76)
Male, n (%)37 (80)20 (87)
Intermediate/poor MSKCC risk, n (%)32 (70)15 (65)
Median lines prior therapy, n (range)3 (2-7)3 (2-5)
≥2 Prior TKI, n (%)33 (72)15 (65)
Prior PD-(L)1 antibody treatment, n (%)42 (91)19 (83)

Conclusions

The addition of tela improved PFS over pboE, w/ tolerable safety profile in heavily treated mRCC pts, including refractory to multiple TKIs and immune checkpoint inhibitors. ENTRATA met its primary endpoint, supporting proof of concept for GLS inhibition w/ tela as a new therapeutic approach in RCC.

Clinical trial identification

NCT03163667; May 23, 2017.

Editorial acknowledgement

Medical writing support was provided by Ingrid Koo, PhD, and funded by Calithera Biosciences, Inc.

Legal entity responsible for the study

Calithera Biosciences, Inc.

Funding

Calithera Biosciences, Inc.

Disclosure

R.J. Motzer: Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Merck; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy: Incyte; Advisory / Consultancy: Lilly; Research grant / Funding (institution): Bristol-Myers Squibb. C. Lee: Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): Exelexis; Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution): BMS; Research grant / Funding (institution): Calithera; Research grant / Funding (institution): Pfizer; Leadership role: Kidney Cancer Association. H. Emamekhoo: Advisory / Consultancy: Exelixis; Advisory / Consultancy: Bayer. M. Matrana: Speaker Bureau / Expert testimony: Merck; Speaker Bureau / Expert testimony: Genentech; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Eisai; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Janssen; Advisory / Consultancy: Strata Oncology. J.J. Hsieh: Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution), Research funding for Kidney Cancer Therapeutics; Institutional funding for clinical trials: Eisai; Advisory / Consultancy, Research grant / Funding (self), Research funding for Kidney Cancer Genomics: Novartis; Research grant / Funding (self), Research funding for Kidney Cancer Genomics: BostonGene; Research grant / Funding (self), Research funding for Kidney Cancer Genomics: Cancer Genetics Inc; Research grant / Funding (institution), Institutional funding for clinical trials: Calithera; Research grant / Funding (institution), Institutional funding for clinical trials: BMS; Research grant / Funding (institution), Institutional funding for clinical trials: Exelixis; Leadership role, Medical Steering Committee: Kidney Cancer Association. A. Hussain: Advisory / Consultancy, Consultant; Site PI for sponsored clinical trial: Bayer; Advisory / Consultancy, Advisory Board: AstraZeneca; Advisory / Consultancy, Consultant: Bristol-Myers Squibb; Advisory / Consultancy, Advisory Board: Exelexis; Research grant / Funding (institution), Site PI for sponsored clinical trial: Sotio; Research grant / Funding (institution), Site PI for sponsored clinical trial: Calithera; Research grant / Funding (institution), Site PI for sponsored clinical trial: Merck; Research grant / Funding (institution), Site PI for sponsored clinical trial: Roche; Research grant / Funding (institution), Site PI for sponsored clinical trial: Constellation; Research grant / Funding (institution), Site PI for sponsored clinical trial: Clovis. U.N. Vaishampayan: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research support: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research support: Exelixis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Research grant / Funding (self), Research support: Novartis; Leadership role, Board Member: Michigan Society of Hematology Oncology. S. Liu: Honoraria (self): Merck; Honoraria (self): Exelixis. S. McCune: Research grant / Funding (institution), PI on this trial for our institution: Calithera. H. Parmar: Shareholder / Stockholder / Stock options, Full / Part-time employment: Calithera Biosciences. Y. Shen: Shareholder / Stockholder / Stock options, Full / Part-time employment: Calithera Biosciences. S.H. Whiting: Shareholder / Stockholder / Stock options, Full / Part-time employment: Calithera Biosciences; Spouse / Financial dependant: Seattle Genetics. N.M. Tannir: Research grant / Funding (self), Research grant / Funding (institution), Principal Investigator on clinical trials; institutional - direct costs on clinical trials: Calithera. All other authors have declared no conflicts of interest.

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Proffered Paper 1 – Genitourinary tumours, non-prostate Proffered Paper session

LBA55 - Initial results from TROPHY-U-01: A phase II open-label study of sacituzumab govitecan in patients (Pts) with metastatic urothelial cancer (mUC) after failure of platinum-based regimens (PLT) or immunotherapy (ID 1900)

Presentation Number
LBA55
Lecture Time
08:45 - 09:00
Speakers
  • Scott T. Tagawa (New York, US, United States of America)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:30 - 10:00

Abstract

Background

Pts with mUC have limited options after progression on PLT/checkpoint inhibitors (CPI). Sacituzumab govitecan (SG) is an antibody-drug conjugate comprising a humanized anti-Trop-2 monoclonal antibody coupled to SN-38 via a unique hydrolysable linker. In a prior phase I/II study, SG showed significant clinical activity and manageable toxicity in 45 heavily pretreated mUC pts (ORR: 31% overall).

Methods

TROPHY-U-01 (NCT03547973) is a global, open-label, phase II trial evaluating the antitumor activity of SG (10 mg/kg, days 1, 8 of 21-day cycles) in pts with mUC with measurable disease, ECOG performance status 0 or 1, and creatinine clearance ≥30 mL/min. This pre-planned interim analysis based on investigator assessment per RECIST v1.1 reports data from Cohort 1 (pts who progressed after both PLT and CPI). Cohort 1 (N = 35) had a Simon two-stage design with a prespecified futility stopping rule of 11% ORR.

Results

35 pts with ≥1 post -baseline response assessment (80% male; median age 64 y [range 43-90], 77% ≥1 Bellmunt risk factors) received a median of 3 (range 2-7) prior therapies. At a median follow-up of 4.1 mon, ORR was 29% (10/35) with 2 confirmed CR, 5 confirmed PR, and 3 unconfirmed PR (all 3 ongoing and awaiting radiographic confirmation); 74% (26/35) of pts had target lesion reduction. ORR was 25% [2/8] in pts with liver involvement. The safety profile was consistent with prior reports. Key Grade ≥3 treatment-related AEs were neutropenia (23%), anemia (17%), febrile neutropenia (11%), diarrhea (11%). No events of interstitial lung disease, ocular toxicities, or grade >2 neuropathy were reported. There were no treatment-related deaths.

Conclusions

Interim Cohort 1 results from TROPHY-U-01 surpassed the pre-specified futility stopping rule and enrollment continues. Findings confirm prior phase I/II study results of SG as well-tolerated with significant antitumor activity in mUC pts after both prior PLT and CPI. In this population that continues to have a high unmet medical need despite recent progress, the ORR of 29% compares favorably with single-agent chemotherapy (ORR of 9%–14%).

Clinical trial identification

NCT03547973 (release date: June 6, 2018).

Editorial acknowledgement

Editorial support was provided by Cindy Gobbel, PhD, of Peloton Advantage, LLC, an OPEN Health company, and funded by Immunomedics, Inc.

Legal entity responsible for the study

Immunomedics Inc.

Funding

Immunomedics Inc.

Disclosure

S.T. Tagawa: Advisory / Consultancy, Research grant / Funding (institution): Medivation; Advisory / Consultancy, Research grant / Funding (institution): Astellas Pharma; Advisory / Consultancy, Research grant / Funding (institution): Dendreon; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Endocyte; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Immunomedics; Advisory / Consultancy, Research grant / Funding (institution): Karyopharm Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): AbbVie; Advisory / Consultancy: Tolmar; Advisory / Consultancy: QED Therapeutics; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Progenics; Research grant / Funding (institution): Millennium; Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Rexahn Pharmaceuticals; Research grant / Funding (institution): Newlink Genetics; Research grant / Funding (institution): Inovio Pharmaceuticals; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): AVEO; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Stemcentrx; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Clovis Oncology. A. Balar: Advisory / Consultancy, Research grant / Funding (institution): Seattle Genetics. D.P. Petrylak: Advisory / Consultancy, Research grant / Funding (institution): Advanced Accelerator Applications; Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Clovis; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Incyte; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Pharmacyclics; Advisory / Consultancy, Research grant / Funding (institution): Roche Laboratories; Advisory / Consultancy, Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Innocrin; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Endocyte; Advisory / Consultancy: Urogen; Research grant / Funding (institution): Progenics; Research grant / Funding (institution): Sanofi Aventis; Research grant / Funding (institution): Merck; Shareholder / Stockholder / Stock options: Bellicum ; Shareholder / Stockholder / Stock options: Tyme. P. Grivas: Research grant / Funding (institution), to University of Washington for clinical trial conduction: Immunomedics; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Non product speaker’s program, fees to CCF for trial and consulting (unrelated to this study): Genentech; Advisory / Consultancy, consulting (unrelated to this study): Dendreon; Advisory / Consultancy, Research grant / Funding (institution), fees to clev. clinic foundation for clin trial conduction and consulting (unrelated): Bayer; Advisory / Consultancy, Research grant / Funding (institution), clinical trial conduction (unrelated to this study), consulting unrelated to this study: Merck & Co.; Research grant / Funding (institution), clinical trial conduction (unrelated to this study): Mirati; Research grant / Funding (institution), fees to clev. clinic foundation for clin trial conduction (unrelated to study) : Oncogenex; Advisory / Consultancy, Research grant / Funding (institution), consulting, fees to CCF and University of Washington for trial conduction (unrelated to study) : Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, consulting and non product related speaker program (unrelated to this study): Bristol-Myers Squibb; Advisory / Consultancy, consulting unrelated to this study: Exelixis; Advisory / Consultancy, Research grant / Funding (institution), consulting and fees to CCF for trial conduction (unrelated to this study): AstraZeneca; Advisory / Consultancy, consulting (unrelated to this study): Biocept; Advisory / Consultancy, Research grant / Funding (institution), consulting (unrelated to this study), to University of Washington for unrelated clinical trial: Clovis Oncology; Advisory / Consultancy, consulting (unrelated to this study): EMD Serono; Advisory / Consultancy, consulting (unrelated to this study): Seattle Genetics; Advisory / Consultancy, consulting (unrelated to this study): Foundation Medicine; Advisory / Consultancy, consulting (unrelated to this study): Driver Inc.; Advisory / Consultancy, consulting (unrelated to this study): QED Therapeutics; Advisory / Consultancy, consulting (unrelated to this study): Heron Therapeutics; Advisory / Consultancy, consulting (unrelated to this study): Janssen; Research grant / Funding (institution), to University of Washington for clinical trial conduction (unrelated to this study): Bavarian Nordic. N. Agarwal: Advisory / Consultancy, Scientific advisory board: Astellas; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: AstraZeneca; Advisory / Consultancy, Scientific advisory board: Argos; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Bayer; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Clovis; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Eisai; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Exelixis; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: EMD Serono; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Eli Lilly; Advisory / Consultancy, Scientific advisory board: Foundation One; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Genentech; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Janssen; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Merck; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Medivation; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Novartis; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Nektar; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Pfizer; Advisory / Consultancy, Scientific advisory board: Pharmacyclics; Research grant / Funding (institution): Bavarian Nordic; Research grant / Funding (institution): Calithera; Research grant / Funding (institution): Celldex; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): New Link Genetics; Research grant / Funding (institution): Prometheus; Research grant / Funding (institution): Rexahn; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Tracon. C.N. Sternberg: Advisory / Consultancy: Merck; Advisory / Consultancy: Clovis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Incyte; Advisory / Consultancy: AstraZeneca; Research grant / Funding (institution): Janssen. Q. Hong: Shareholder / Stockholder / Stock options, Full / Part-time employment: Immunomedics; Shareholder / Stockholder / Stock options: Bristol-Myers Squibb; Shareholder / Stockholder / Stock options, Full / Part-time employment, Spouse / Financial dependant, Spouse employment and stock ownership: Merck & Co.; Travel / Accommodation / Expenses: Advaxis Inc. A. Gladden: Full / Part-time employment, Clinical Operations Study Lead: Immunomedics. C. Kanwal: Full / Part-time employment: Immunomedics, Inc.. P. Siemon-Hryczyk: Shareholder / Stockholder / Stock options, Full / Part-time employment: Immunomedics. T. Goswami: Full / Part-time employment: Immunomedics. L.M. Itri: Advisory / Consultancy: Immunomedics, Inc. . Y. Loriot: Non-remunerated activity/ies, Investigator: Immunomedics; Advisory / Consultancy, Travel / Accommodation / Expenses, Non-remunerated activity/ies, Fees for consulting, travel paid, investigator: AstraZeneca; Advisory / Consultancy, Non-remunerated activity/ies, Fees for consulting, investigator: Clovis; Advisory / Consultancy, Travel / Accommodation / Expenses, Non-remunerated activity/ies, Fees for consulting and travel paid, investigator: Seattle Genetics; Speaker Bureau / Expert testimony, Non-remunerated activity/ies, Lectures, investigator: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies, Fees for consulting, lectures, travel, investigator: Janssen; Advisory / Consultancy, Non-remunerated activity/ies, Fees for consulting, investigator: Incyte; Advisory / Consultancy, Non-remunerated activity/ies, Fees for consulting, lectures and travel paid, investigator: Roche; Speaker Bureau / Expert testimony, Non-remunerated activity/ies, Fees for lecture, investigator: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies, Fees for consulting, lectures and travel paid, investigator: MSD; Advisory / Consultancy, Non-remunerated activity/ies, Fees for consulting, investigator: Nektar; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Non-remunerated activity/ies, Fees for consulting, lectures and travel paid, investigator: Bristol-Myers Squibb.

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Proffered Paper 1 – Genitourinary tumours, non-prostate Proffered Paper session

Invited Discussant LBA54 and LBA55 (ID 6730)

Lecture Time
09:00 - 09:15
Speakers
  • Ignacio Duran Martinez (Santander, Spain)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:30 - 10:00
Proffered Paper 1 – Genitourinary tumours, non-prostate Proffered Paper session

901O - EV-103: Initial results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma (ID 4844)

Presentation Number
901O
Lecture Time
09:15 - 09:30
Speakers
  • Christopher J. Hoimes (Cleveland, United States of America)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:30 - 10:00

Abstract

Background

Platinum-based chemotherapy remains the standard of care for patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC). Despite the use of first-line (1L) PD-1/PD-1L inhibitors, 71–76% of pts who are cisplatin-ineligible do not respond. EV is an antibody-drug conjugate targeting Nectin-4, which is highly expressed in mUC. EV monotherapy data are encouraging; combination therapy may provide additional benefit. Here, we report initial data on a cohort of cis-ineligible pts receiving 1L EV + pembrolizumab.

Methods

This phase 1b study (NCT03288545) evaluated the safety/activity of EV + pembrolizumab. In the dose-escalation cohort, 1L or 2L pts received 1.0 or 1.25 mg/kg EV + 200 mg pembrolizumab. Cohort A pts received the recommended dose of 1.25 mg/kg EV + pembrolizumab as 1L therapy. In each 21-day cycle, EV was administered on Days 1 and 8 and pembrolizumab on Day 1. The primary endpoint was safety/tolerability; key secondary objectives: recommended EV dose, antitumor activity, DCR, DOR, PFS, and OS.

Results

As of 20 Feb 2019, 29 la/mUC pts (median 68 [51–90] y; 31% liver metastasis, 17% ECOG 2) have been treated with EV (1.25 mg/kg) + pembrolizumab in the 1L setting and completed at least 2 post-baseline scans or discontinued treatment. The most common treatment-emergent adverse events (AE) were fatigue (66%, 14% ≥Grade 3), decreased appetite (52%, 0% ≥Grade 3), alopecia (45%), and diarrhea (41%, 3% ≥Grade 3). Among AE of clinical interest, rash of any type occurred in 45% of pts (14% ≥Grade 3), peripheral neuropathy of any type in 52% (3% ≥Grade 3), and 17% experienced immune-mediated events that required systemic steroid treatment (10% ≥Grade 3). Overall, 2 pts (7%) discontinued treatment with EV + pembrolizumab due to AE (lipase increase,multi-organ failure). Preliminary confirmed ORR per RECIST 1.1 was 62% by investigators, including a 14% CR rate. The DCR was 90%.

Conclusions

In 1L cis-ineligible pts with la/mUC, EV + pembrolizumab demonstrates encouraging efficacy with a tolerable and manageable safety profile. Further evaluation of this combination is warranted. Updated data, including responses pending confirmation, will be available at the meeting.

Clinical trial identification

NCT03288545.

Editorial acknowledgement

Heather Brignull, PhD of Seattle Genetics.

Legal entity responsible for the study

Seattle Genetics, Inc.

Funding

Seattle Genetics, Inc. Astellas Pharma, Inc, and Merck.

Disclosure

C.J. Hoimes: Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy: Eisai; Advisory / Consultancy: Foundation Medicine; Advisory / Consultancy, Speaker Bureau / Expert testimony: Genentech; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Prometheus Labs; Honoraria (self), Advisory / Consultancy: Seattle Genetics. J.E. Rosenberg: Advisory / Consultancy: Adicet Bio; Advisory / Consultancy, Research grant / Funding (institution): Agensys; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: BioClin Therapeutics; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: EMD Serono; Advisory / Consultancy: Fortress Biotech; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech; Advisory / Consultancy: Inovio Pharma; Honoraria (self): Eli Lilly; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Merck; Advisory / Consultancy: Pharmacyclics; Advisory / Consultancy: QED Therapeutics; Advisory / Consultancy: Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Seattle Genetics; Advisory / Consultancy: Sensei Biotherapeutics; Advisory / Consultancy: Western Oncolytics; Shareholder / Stockholder / Stock options: Illumina; Honoraria (self): Chugai Pharma. S. Srinivas: Advisory / Consultancy: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Seattle Genetics. D.P. Petrylak: Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Bellicum Pharm; Advisory / Consultancy, Research grant / Funding (institution): Dendreon; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Ferring; Advisory / Consultancy, Research grant / Funding (institution): Johnson & Johnson; Advisory / Consultancy, Research grant / Funding (self): Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution): Millennium; Advisory / Consultancy: Medivation; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Tyme; Advisory / Consultancy, Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Agensys; Speaker Bureau / Expert testimony: Celgene; Research grant / Funding (institution): Clovis Oncology; Research grant / Funding (institution): Genentech. M. Milowsky: Research grant / Funding (institution): Mirati Therapeutics; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Cerulean Pharm; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Acerta Pharma; Research grant / Funding (institution): BioClin Therapeutics; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): X4 Pharma; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Innocrin Pharma; Research grant / Funding (institution): Inovio Pharmaceuticals. J.R. Merchan: Research grant / Funding (institution): Seattle Genetics; Advisory / Consultancy: Exelixis; Research grant / Funding (institution): Rexahn; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Tocagen; Research grant / Funding (institution): Agensys; Research grant / Funding (institution): Tracon. M.A. Bilen: Advisory / Consultancy: Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Nektar; Advisory / Consultancy: Genomic Health; Advisory / Consultancy, Research grant / Funding (institution): Seattle Genetics; Advisory / Consultancy: Sanofi; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Tricon Pharmaceuticals; Research grant / Funding (institution): Peleton; Research grant / Funding (institution): Pfizer. S. Gupta: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Genentech; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Innocrin Pharma; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Merck. A. Carret: Honoraria (self), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Seattle Genetics. N. Yuan: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Seattle Genetics. A. Melhem-Bertrandt: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Astellas. T. Flaig: Advisory / Consultancy: GTX; Leadership role, Shareholder / Stockholder / Stock options, Officer / Board of Directors: Aurora Oncology; Honoraria (self): BN ImmunoTherapeutics; Research grant / Funding (institution): Agensys; Research grant / Funding (institution): Aragon Pharma; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Bavarian Nordic; Research grant / Funding (institution): Dendreon; Research grant / Funding (institution): Exelisix; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): GTx; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): La Roche-Posay; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Pfizer.

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Proffered Paper 1 – Genitourinary tumours, non-prostate Proffered Paper session

902O - An adaptive, biomarker directed platform study in metastatic urothelial cancer (BISCAY) with durvalumab in combination with targeted therapies (ID 4397)

Presentation Number
902O
Lecture Time
09:30 - 09:45
Speakers
  • Thomas B. Powles (London, United Kingdom)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:30 - 10:00

Abstract

Background

Durvalumab (D), a PD-L1 inhibitor with efficacy in platinum refractory advanced urothelial cancer (UC), was investigated by combining with targeted therapy inhibitors (FGFR1,2,3, PARP, TORC 1 + 2) with a PD-L1 monotherapy arm (D alone) as a non-randomized control. An FGFRi monotherapy arm was also included.

Methods

Platinum refractory, immuno-therapy naïve UC patients were allocated, depending on tumour DNA alterations determined by next generation sequencing (NGS), to: arm A (randomisation of D + FGFRi AZD4547 vs AZD4547 monotherapy: for FGFR mutations/fusions), arm B (D + PARPi olaparib: for BRCA1/2, ATM and HRR gene alterations (GA) and unselected patients), arm E (D + mTORi vistusertib: enriched for TSC1/2 and RICTOR GA). Arm D (D only) followed by Arm F (D + STAT3 mRNA ASO danvatirsen) for patients without “actionable” GA. Primary objectives included safety and tolerability. Key secondary objectives included assessment of ORR and OS rate. Efficacy analysis was explored based on PD-L1 expression and tumour mutational burden (TMB).

Results

As of March 2019, of 393 patients’ whose tumours were screened with NGS, 154 started study drug and had a baseline tumor assessment. Confirmed responses were assessed according to RECIST 1.1 and ranged from 20% to 29% (Table). TMB and PD-L1 were inconsistent across arms (e.g. 38% TMB high for Arm E vs 5% in Arm A combination and 17% in Arm D). D monotherapy (n = 29) had an ORR of 28% [80% CI 17% - 41%] with 12% [80% CI 3.2% - 28%] and 45% [80% CI 24% - 63%] of patients alive and progression free and alive at 12 months, respectively. Complete responses were not prominent in any study arm. Arms A, D and E completed earlier than arms B and F. Data will be updated based on additional follow-up.

902O

AZD4547 (A)AZD4547 + durvalumab (A)Vistusertib + durvalumab (E)durvalumab (D)
N15212929
PD-L1+ve27%33%38%41%
TMB high > 10M/MB20%5%38%17%
ORR (RECIST1.1) 80% CI20% 7.6%; 39%29% 16%; 45%21% 11%; 34%28% 17%; 41%
Discontinued due to AE20%33%38%10%

Conclusions

Combination treatments with durvalumab are tolerated. Clinical activity was seen in all arms of the study including both biomarker-selected and unselected individuals.

Clinical trial identification

NCT02546661; 11-Sep-2015.

Legal entity responsible for the study

AstraZeneca AB, 151 85 Södertälje, Sweden.

Funding

AstraZeneca.

Disclosure

T. Powles: Honoraria (self): AstraZeneca, Roche, MSD, Pfizer, Novartis, Seattle Genetics, Ipsen; Research grant / Funding (institution): AstraZeneca, Roche, MSD. A. Balar: Honoraria (self): AstraZeneca; Roche-Genentech; Merck; Advisory / Consultancy: AstraZeneca, Genentech/Roche, Merck, Incyte, Seattle Genetics, DragonFly, Nektar; Research grant / Funding (institution): Merck, Genentech/Roche, Seattle Genetics, Bristol-Myers Squibb, AstraZeneca, Nektar; Shareholder / Stockholder / Stock options: EpiVax Oncology. G. Gravis: Travel / Accommodation / Expenses: BMS; Pfizer; Janssen; Ipsen. R. Jones: Honoraria (self): AstraZeneca; MSD; Merck Serono; Roche; BMS; Janssen; Astellas; Honoraria (institution): AstraZeneca, Janssen, Astellas; Advisory / Consultancy: AstraZeneca; MSD; Roche; BMS; Pfizer; Janssen; Astellas; Research grant / Funding (institution): Roche; Pfizer; AstraZeneca; Travel / Accommodation / Expenses: BMS; MSD; Astellas. A. Ravaud: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; BMS; AstraZeneca; Roche; MSD; Ipsen; Research grant / Funding (institution): Pfizer. J. Florence: Advisory / Consultancy: Roche; Ipsen; AstraZeneca; Janssen; Tesaro; BMS; Pfizer; Novartis; Sanofi; Astellas; Research grant / Funding (institution): Astellas; Travel / Accommodation / Expenses: Roche; Ipsen; AstraZeneca; Janssen; Tesaro; BMS. P. Grivas: Advisory / Consultancy: Merck & Co; Genentech; Dendreon; Bayer; Pfizer; Bristol-Myers Squibb; Exelixis; AstraZeneca; Biocept; Clovis Oncology; EMD Serono; Seattle Genetics; Foundation Medicine; Driver Inc.; QED Therapeutics; Heron Therapeutics; Janssen; Speaker Bureau / Expert testimony: Genentech; Bristol-Myers Squibb;; Travel / Accommodation / Expenses: AstraZeneca; Clovis Oncology; Research grant / Funding (institution): Merck & Co.; Genentech; Bayer; Mirati; Oncogenex; AstraZeneca; Pfizer; Clovis Oncology; Bavarian Nordic; Immunomedics. D.P. Petrylak: Advisory / Consultancy: Ada Cap (Advanced Accelerator Applications), Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myer Squibb, Clovis, Eli Lilly, Exelixis, Incyte, Janssen, Pfizer, Pharmacyclics, Roche Laboratories, Seattle Genetics, Urogen; Research grant / Funding (institution): Ada Cap (Advanced Accelerator Applications), Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Clovis, Eli Lilly, Endocyte, Genentech, Innocrin, MedImmune, Merck, Novartis, Pfizer, Progenics, Roche Laboratories, Sanofi Aventis, Seattle Genetics; Shareholder / Stockholder / Stock options: Bellicum, Tyme. M. Galsky: Advisory / Consultancy: AstraZeneca, BMS, Genentech, Merck, Pfizer, Dracen, Dragonfly Therapeutics, Astellas, Seattle Genetics, Janssen; Research grant / Funding (institution): AstraZeneca, BMS, Merck, Dendreon, Roche-Genentech. J. Carles: Advisory / Consultancy: Bayer; Johnson & Johnson; Bristol-Myers Squibb; Astellas Pharma; Pfizer; Sanofi; MSD Oncology; Roche; AstraZeneca; Speaker Bureau / Expert testimony: Bayer; Johnson & Johnson; Asofarma; Astellas Pharma; Research grant / Funding (institution): AB Science, Aragon Pharmaceuticals, Arog Pharmaceuticals, INC, Astellas Pharma, AstraZeneca AB, Aveo Pharmaceuticals INC, Bayer AG, Blueprint Medicines Corporation, BN Immunotherapeutics INC, Boehringer Ingelheim España, S.A., Bristol-Myers Squibb Intern. S. Sridhar: Advisory / Consultancy: AstraZeneca, Roche, Merck, BMS, Bayer, Janssen, Astellas. H. Arkenau: Leadership role: Sarah Cannon Research Institute; Research grant / Funding (self): AstraZeneca; Roche; BMS; Novartis; GSK; Servier; Astellas; Array; Iovance; Cytomx; Research grant / Funding (institution): Sarah Cannon Research Institute; Travel / Accommodation / Expenses: Iovance. D. Carroll: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca; Spouse / Financial dependant: Azeria Therapeutics. J. DeCesare: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. F. Mercier: Full / Part-time employment: AstraZeneca; Shareholder / Stockholder / Stock options: Stat Process sarl (Paris, France) - CRO; Health Data Process (Alicante, Spain) - CRO. D. Hodgson: Shareholder / Stockholder / Stock options, Non-remunerated activity/ies: AstraZeneca. J. Stone: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca; Shareholder / Stockholder / Stock options: GSK. J. Cosaert: Full / Part-time employment: AstraZeneca. D. Landers: Research grant / Funding (institution): Clinical Experimental Pharmacology Group, CRUK Manchester Institute, Manchester, UK; AstraZeneca; Full / Part-time employment: AstraZeneca.

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Proffered Paper 1 – Genitourinary tumours, non-prostate Proffered Paper session

Invited Discussant 901O and 902O (ID 6731)

Lecture Time
09:45 - 10:00
Speakers
  • Yohann Loriot (Villejuif, France)
Location
Barcelona Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
08:30 - 10:00