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LBA23 - EPIK-P1: Retrospective chart review study of patients (pts) with PIK3CA -related Overgrowth Spectrum (PROS) who have received alpelisib (ALP) as part of a compassionate use programme
- Guillaume Canaud (Paris, France)
Abstract
Background
PROS is a group of rare, heterogeneous disorders resulting from activating somatic mutations in the
Methods
EPIK-P1 is a retrospective non-interventional medical chart review of pts (age ≥2 years) with PROS treated with ALP. Pts had a diagnosis of PROS, severe or life-threatening conditions, confirmed
Results
Data were abstracted from 57 pts (39 paediatric, 18 adult) at 7 sites in 5 countries. Median length of exposure (start of tx to last tx per cutoff date) was 18.1 mo. In the primary endpoint analysis at week 24, 37.5% (95% CI, 21.1-56.3%) of pts (12/32 of the complete cases) responded; sensitivity analysis showed similar results. Of the 12 responders, none experienced disease progression or death by data cutoff. 23 out of 31 pts (74.2%) reported reduction in sum of target lesion volume with mean reduction of 13.7%. At week 24, proportion of pts with improvement in the most frequent (in the full-study population) PROS-related symptoms/signs was pain 90.9% (20/22), fatigue 76.2% (32/42), vascular malformation 78.9% (30/38), limb asymmetry 69.0% (20/29), and disseminated intravascular coagulation 55.2% (16/29). In the first 24 weeks, there were no surgeries due to disease progression. Adverse events (AEs) and tx-related AEs were experienced by 82.5% (n=47) and 38.6% (n=22) of pts, respectively; no deaths were reported. The most common tx-related AEs were hyperglycaemia (n=7, 12.3%), aphthous ulcer (n=6, 10.5%), and stomatitis (n=3, 5.3%).
Conclusions
The real-world evidence from the EPIK-P1 study demonstrates that ALP confers clinically meaningful efficacy to, and is well tolerated in, pts with PROS.
Clinical trial identification
NCT04285723.
Editorial acknowledgement
We thank Rob Camp, PhD, and Kymberleigh Romano, PhD, of Healthcare Consultancy Group, LLC, for their medical editorial assistance with this abstract, which was funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
G. Canaud: Financial Interests, Personal, Other, Consulting fees & Travel support: Novartis Pharmaceuticals Corporation; Financial Interests, Personal, Other, Consulting fees: Bridgebio; Other, Personal and Institutional, Other, Patent pending WO2017140828A1: Hôpital Necker, Université de Paris; Financial Interests, Personal, Other, Consulting fees: Fresenius Medical Care. J.C. López Gutiérrez: Financial Interests, Personal, Speaker’s Bureau, Travel support and speakers' bureau fees: Pierre Fabre Pharmaceuticals. A. Irvine: Financial Interests, Personal, Speaker’s Bureau, Consulting fees: AbbVie; Financial Interests, Personal, Other, Consulting fees: Arena Pharmaceuticals; Financial Interests, Personal, Other, Consulting fees: Benevolent AI; Financial Interests, Personal, Other, Consulting fees: Chugai; Financial Interests, Personal, Other, Consulting fees: Dermavant; Financial Interests, Personal, Other, Consulting fees: Genentech; Financial Interests, Personal, Speaker’s Bureau, Consulting fees: LEO Pharma; Financial Interests, Personal, Speaker’s Bureau, Consulting fees: Lilly; Financial Interests, Personal, Other, Consulting fees: Menlo Therapeutics; Financial Interests, Personal, Speaker’s Bureau, Consulting fees: Novartis; Financial Interests, Personal, Speaker’s Bureau, Consulting fees: Pfizer; Financial Interests, Personal, Speaker’s Bureau, Consulting fees: Regeneron; Financial Interests, Personal, Speaker’s Bureau, Consulting fees: Sanofi; Financial Interests, Personal, Other, Consulting fees: UCB. N. Ankrah: Financial Interests, Personal, Full or part-time Employment: Novartis Pharmaceuticals Corporation. A. Papadimitriou: Financial Interests, Personal, Full or part-time Employment: Novartis Pharmaceuticals Corporation. A. Ridolfi: Financial Interests, Personal, Full or part-time Employment: Novartis Pharma S.A.S. D.M. Adams: Financial Interests, Personal, Other, Consulting fees: Novartis Pharmaceuticals Corporation; Financial Interests, Personal, Other, Consulting fees: Venthera.
512O - Interim results from a phase II study of the ATR inhibitor ceralasertib in ARID1A-deficient and ARID1A-intact advanced solid tumor malignancies
- Rahul Aggarwal (San Francisco, United States of America)
Abstract
Background
Loss of
Methods
Patients (pts) with advanced solid tumor malignancies were enrolled.
Results
Of screened pts whose tumors harbored pathogenic mutations in
Conclusions
We observed anti-tumor activity with single agent ceralasertib in
Clinical trial identification
NCT03682289.
Legal entity responsible for the study
University of California San Francisco.
Funding
AstraZeneca.
Disclosure
S. Smith: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. N. Shah: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. E. Dean: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. All other authors have declared no conflicts of interest.
Invited Discussant LBA23 and 512O
- Christophe Massard (Villejuif, France)
Q&A and live discussion
- Christophe Massard (Villejuif, France)
513O - A phase I/II multicenter, first-in-human study of DS-7300 (B7-H3 DXd-ADC) in patients (pts) with advanced solid tumors
- Melissa L. Johnson (Nashville, TN, United States of America)
Abstract
Background
B7-H3 overexpression is associated with poor prognosis in various cancers. DS-7300 is an antibody drug conjugate composed of an anti–B7-H3 IgG1 monoclonal antibody conjugated to an exatecan derivative payload with a drug to antibody ratio of ∼4. It has shown potent preclinical antitumor activity. Here, we report preliminary results from a phase 1/2 trial of DS-7300 in pts with advanced solid tumors.
Methods
This dose-escalation (part 1) and -expansion (part 2) study is recruiting adult pts with 11 selected tumor types in the US and Japan. DS-7300, from 0.8 to 16 mg/kg IV, is administered every 3 wk. Part 1 assesses safety, tolerability, and maximum tolerated or recommended dose for expansion; additional pts were enrolled to examine safety and efficacy. Part 2 assesses safety and prospective efficacy.
Results
Part 1 results are presented. At data cutoff (Apr 9, 2021), 56 pts had enrolled: Median treatment duration, 12 wk (range, 3.0-47.9 wk), with 26 pts (46%) ongoing; median age, 65 y (range, 35-77 y); 42 pts (75%) were male. Baseline B7-H3 expression was highly prevalent in the study population. No DLTs were observed. Treatment-emergent adverse events (TEAEs) occurred in 55 pts (98%). The most common (≥20%) all-grade (Gr) TEAEs were nausea (48%), infusion-related reactions (IRRs; 36%), decreased appetite and vomiting (27% each). Gr ≥3 TEAEs occurred in 11 pts (20%); the most common was anemia (11%). One Gr 3 treatment-related AE (TRAE), neutropenia, occurred. No serious TRAEs occurred. IRRs were Gr 1/2 and manageable with supportive care. Due to TEAEs, 2 pts each (4%) had a dose interruption or reduction, and no dose discontinuations occurred. Two pts died due to disease progression. Among 56 pts enrolled, 9 partial responses (PRs; 5 confirmed PRs [2 CRPC, 1 esophageal SCC (ESCC), 1 sqNSCLC, 1 SCLC], and 4 unconfirmed PRs [1 CRPC, 1 ESCC, 1 SCLC, and 1 endometrial cancer]) were observed, with 6 PRs ongoing; 28 pts had stable disease.
Conclusions
DS-7300 was generally well tolerated with early signs of clinical activity, including objective responses, in pts with pretreated advanced solid tumors. Expansion cohorts are currently enrolling to evaluate DS-7300 in selected tumor types.
Clinical trial identification
NCT04145622. Release date: October 30, 2019.
Editorial acknowledgement
Medical writing support was provided by Neil Gillette, PharmD, of SciMentum, a Nucleus Global company, and was funded by Daiichi Sankyo, Inc.
Legal entity responsible for the study
Daiichi Sankyo, Inc.
Funding
Daiichi Sankyo, Inc.
Disclosure
M.L. Johnson: Financial Interests, Personal, Advisory Role: Otsuka; Financial Interests, Institutional, Advisory Role: Genentech/Roche; Financial Interests, Institutional, Advisory Role: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Advisory Role: Calithera Biosciences; Financial Interests, Institutional, Advisory Role: Merck; Financial Interests, Institutional, Advisory Role: Loxo; Financial Interests, Institutional, Advisory Role: Sanofi; Financial Interests, Institutional, Advisory Role: Mirati Therapeutics; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Advisory Role: Guardant Health; Financial Interests, Institutional, Advisory Role: Ribon Therapeutics; Financial Interests, Institutional, Advisory Role: Incyte; Financial Interests, Institutional, Advisory Role: Abbvie; Financial Interests, Institutional, Advisory Role: Achilles Therapeutics; Financial Interests, Institutional, Advisory Role: Atreca; Financial Interests, Institutional, Advisory Role: GlaxoSmithKline; Financial Interests, Institutional, Advisory Role: Gritstone Oncology; Financial Interests, Institutional, Advisory Role: Janssen Oncology; Financial Interests, Institutional, Advisory Role: Lilly; Financial Interests, Institutional, Advisory Role: Novartis; Financial Interests, Institutional, Advisory Role: Association of Community Cancer Centers (ACCC); Financial Interests, Institutional, Advisory Role: Amgen; Financial Interests, Institutional, Advisory Role: Bristol-Myers Squibb; Financial Interests, Institutional, Advisory Role: Daiichi Sankyo; Financial Interests, Institutional, Advisory Role: EMD Serono; Financial Interests, Institutional, Advisory Role: G1 Therapeutics; Financial Interests, Institutional, Advisory Role: WindMIL; Financial Interests, Institutional, Advisory Role: Checkpoint Therapeutics; Financial Interests, Institutional, Advisory Role: Eisai; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Abbvie; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Genentech; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Incyte; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merck; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Sanofi; Financial Interests, Institutional, Research Grant: EMD Serono; Financial Interests, Institutional, Research Grant: Kadmon; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Mirati Therapeutics; Financial Interests, Institutional, Research Grant: Genmab; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Stem CentRx; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Checkpoint Therapeutics; Financial Interests, Institutional, Research Grant: Array BioPharma; Financial Interests, Institutional, Research Grant: Regeneron; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Hengrui Pharmaceutical; Financial Interests, Institutional, Research Grant: Lycera; Financial Interests, Institutional, Research Grant: BeiGene; Financial Interests, Institutional, Research Grant: Tarveda Therapeutics; Financial Interests, Institutional, Research Grant: Loxo; Financial Interests, Institutional, Research Grant: Abbvie; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Guardant Health; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: CytomX Therapeutics; Financial Interests, Institutional, Research Grant: Dynavax Technologies; Financial Interests, Institutional, Research Grant: Corvus Pharmaceuticals; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Genocea Biosciences; Financial Interests, Institutional, Research Grant: Gritstone Oncology; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Institutional, Research Grant: Adaptimmune; Financial Interests, Institutional, Research Grant: Syndax; Financial Interests, Institutional, Research Grant: Neovia Oncology; Financial Interests, Institutional, Research Grant: Acerta Pharma; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Shattuck Labs; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: Apexigen; Financial Interests, Institutional, Research Grant: Atreca; Financial Interests, Institutional, Research Grant: OncoMed; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Immunocore; Financial Interests, Institutional, Research Grant: Jounce Therapeutics; Financial Interests, Institutional, Research Grant: University of Michigan; Financial Interests, Institutional, Research Grant: WindMIL; Financial Interests, Institutional, Research Grant: TCR2 Therapeutics; Financial Interests, Institutional, Research Grant: Arcus Biosciences; Financial Interests, Institutional, Research Grant: Ribon Therapeutics; Financial Interests, Institutional, Research Grant: BerGenBio; Financial Interests, Institutional, Research Grant: Calithera Biosciences; Financial Interests, Institutional, Research Grant: Tmunity Therapeutics, Inc.; Financial Interests, Institutional, Research Grant: Seven and Eight Biopharmaceuticals; Financial Interests, Institutional, Research Grant: Rubius Therapeutics; Financial Interests, Institutional, Research Grant: Curis; Financial Interests, Institutional, Research Grant: Silicon Therapeutics; Financial Interests, Institutional, Research Grant: Dracen; Financial Interests, Institutional, Research Grant: PMV Pharma; Financial Interests, Institutional, Research Grant: Artios. T. Doi: Financial Interests, Institutional, Principal Investigator: Lilly; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator: Sumitomo Dainippon; Financial Interests, Institutional, Principal Investigator: Taiho; Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Institutional, Principal Investigator: Merck Serono; Financial Interests, Institutional, Principal Investigator: Janssen; Financial Interests, Institutional, Principal Investigator: Boehringer Ingelheim; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Principal Investigator: Abbvie; Financial Interests, Institutional, Principal Investigator: IQVIA; Financial Interests, Institutional, Principal Investigator: Eisai; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Abbvie; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Astellas. S.A. Piha-Paul: Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Institutional, Research Grant: Abbvie; Financial Interests, Institutional, Research Grant: Aminex; Financial Interests, Institutional, Research Grant: Biomarin; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Cerulean Pharma; Financial Interests, Institutional, Research Grant: Chugai Pharma; Financial Interests, Institutional, Research Grant: Curis; Financial Interests, Institutional, Research Grant: Five Prime Therapeutics; Financial Interests, Institutional, Research Grant: Genmab; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: Helix BioPharma; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Jacobio; Financial Interests, Institutional, Research Grant: MedImmune; Financial Interests, Institutional, Research Grant: Medivation; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pieris Pharmaceuticals; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Principa Biopharma; Financial Interests, Institutional, Research Grant: Puma Biotechnology; Financial Interests, Institutional, Research Grant: RAPT Therapeutics; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Taiho Oncology; Financial Interests, Institutional, Research Grant: Tesaro; Financial Interests, Institutional, Research Grant: TransThera Biosciences; Financial Interests, Institutional, Research Grant: XuanZhu; Financial Interests, Institutional, Research Grant: Amphivena Therapeutics; Financial Interests, Institutional, Research Grant: Alkermes; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: ABM Therapeutics, Inc.; Financial Interests, Institutional, Research Grant: Acepodia, Inc.; Financial Interests, Institutional, Research Grant: ENB Therapeutics; Financial Interests, Institutional, Research Grant: Gene Quantum; Financial Interests, Institutional, Research Grant: Silverback Therapeutics; Financial Interests, Institutional, Research Grant: NCI/NIH P30CA016672. S. Sen: Financial Interests, Personal, Full or part-time Employment: Roche/Genentech; Financial Interests, Personal, Stocks/Shares: Roche/Genentech; Financial Interests, Institutional, Research Grant: Loxo; Financial Interests, Institutional, Research Grant: Exelixis; Financial Interests, Institutional, Research Grant: BioAtla; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Epizyme; Financial Interests, Institutional, Research Grant: Fujifilm; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: Tesaro; Financial Interests, Institutional, Research Grant: Synthorx; Financial Interests, Institutional, Research Grant: Xencor; Financial Interests, Institutional, Research Grant: Cyteir; Financial Interests, Institutional, Research Grant: Turning Point Therapeutics; Financial Interests, Institutional, Research Grant: Abbisko; Financial Interests, Institutional, Research Grant: Oncorus. T. Shimizu: Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharma; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Takeda; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: Chugai Pharma; Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Takeda/Millennium; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Five Prime Therapeutics; Financial Interests, Institutional, Research Grant: PharmaMar; Financial Interests, Institutional, Research Grant: 3D Medicines; Financial Interests, Institutional, Research Grant: SymBio Pharmaceuticals; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Chordia Therapeutics; Financial Interests, Institutional, Research Grant: Astellas Pharma. B. Cheng: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc.. N. Yoshizuka: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc.. N. Okamoto: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc.; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo, Inc.; Financial Interests, Personal, Stocks/Shares, An Immediate Family Member: Daiichi Sankyo, Inc.; Financial Interests, Personal, Stocks/Shares, An Immediate Family Member: Takeda; Financial Interests, Personal, Stocks/Shares, An Immediate Family Member: Astellas Pharma. Y. Okuda: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Co., LTD. X. Qian: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc.; Financial Interests, Personal, Other, Equity Ownership: Daiichi Sankyo, Inc.. G. Serbest: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc.. W.E. Brady: Financial Interests, Personal, Full or part-time Employment: Sarah Cannon; Financial Interests, Personal, Full or part-time Employment, (Spouse) Employment: State University of New York at Buffalo; Financial Interests, Personal, Other, (Spouse) Consultancy (Includes expert testimony): Fred Hutchinson Cancer Center. M.R. Patel: Financial Interests, Institutional, Research Grant: Daiichi Sankyo, Inc.. J.C. Bendell: Financial Interests, Institutional, Advisory Role: Gilead Sciences; Financial Interests, Institutional, Advisory Role: Genentech/Roche; Financial Interests, Institutional, Advisory Role: Bristol-Myers Squibb; Financial Interests, Institutional, Advisory Role: Five Prime Therapeutics; Financial Interests, Institutional, Advisory Role: Lilly; Financial Interests, Institutional, Advisory Role: Merck; Financial Interests, Institutional, Advisory Role: MedImmune; Financial Interests, Institutional, Advisory Role: Celgene; Financial Interests, Institutional, Advisory Role: EMD Serono; Financial Interests, Institutional, Advisory Role: Taiho Pharmaceutical; Financial Interests, Institutional, Advisory Role: Macrogenics; Financial Interests, Institutional, Advisory Role: GlaxoSmithKline; Financial Interests, Institutional, Advisory Role: Novartis; Financial Interests, Institutional, Advisory Role: OncoMed; Financial Interests, Institutional, Advisory Role: Leap Therapeutics; Financial Interests, Institutional, Advisory Role: TG Therapeutics; Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Advisory Role: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Role: Daiichi Sankyo; Financial Interests, Institutional, Advisory Role: Bayer; Financial Interests, Institutional, Advisory Role: Incyte; Financial Interests, Institutional, Advisory Role: Apexigen; Financial Interests, Institutional, Advisory Role: Array BioPharma; Financial Interests, Institutional, Advisory Role: Sanofi; Financial Interests, Institutional, Advisory Role: ARMO BioSciences; Financial Interests, Institutional, Advisory Role: Ipsen; Financial Interests, Institutional, Advisory Role: Merrimack; Financial Interests, Institutional, Advisory Role: Oncogenex; Financial Interests, Institutional, Advisory Role: FORMA Therapeutics; Financial Interests, Institutional, Advisory Role: Arch Oncology; Financial Interests, Institutional, Advisory Role: Prelude Therapeutics; Financial Interests, Institutional, Advisory Role: Phoenix Biotech; Financial Interests, Institutional, Advisory Role: Cyteir; Financial Interests, Institutional, Advisory Role: Molecular Partners; Financial Interests, Institutional, Advisory Role: Innate Pharma; Financial Interests, Institutional, Advisory Role: Torque; Financial Interests, Institutional, Advisory Role: Tizona Therapeutics, Inc.; Financial Interests, Institutional, Advisory Role: Janssen; Financial Interests, Institutional, Advisory Role: Tolero Pharmaceuticals; Financial Interests, Institutional, Advisory Role: TD2; Financial Interests, Institutional, Advisory Role: Amgen; Financial Interests, Institutional, Advisory Role: Seattle Genetics; Financial Interests, Institutional, Advisory Role: Moderna Therapeutics; Financial Interests, Institutional, Advisory Role: Tanabe Research; Financial Interests, Institutional, Advisory Role: Beigene; Financial Interests, Institutional, Advisory Role: Continuum Clinical; Financial Interests, Institutional, Advisory Role: Cerulean Pharma; Financial Interests, Institutional, Advisory Role: Kyn Therapeutics; Financial Interests, Institutional, Advisory Role: Bicycle Therapeutics; Financial Interests, Institutional, Advisory Role: Relay Therapeutics; Financial Interests, Institutional, Advisory Role: Evelo Therapeutics; Financial Interests, Institutional, Advisory Role: Fusion Pharmaceuticals; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merck; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche/Genentech; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Celgene; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Daiichi Sankyo; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Gilead Sciences; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol-Myers Squibb; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Lilly; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MedImmune; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Taiho Pharmaceutical; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Novartis; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: OncoMed; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Boehringer Ingelheim; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: ARMO BioSciences; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Ipsen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: FORMA Therapeutics; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Gilead Sciences; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Leap Therapeutics; Financial Interests, Institutional, Research Grant: AstraZeneca/MedImmune; Financial Interests, Institutional, Research Grant: Boston Biomedical; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Array BioPharma; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: Celgene; Financial Interests, Institutional, Research Grant: OncoMed; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Apexigen; Financial Interests, Institutional, Research Grant: Kolltan Pharmaceuticals; Financial Interests, Institutional, Research Grant: SynDevRx; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Macrogenics; Financial Interests, Institutional, Research Grant: Five Prime Therapeutics; Financial Interests, Institutional, Research Grant: EMD Serono; Financial Interests, Institutional, Research Grant: TG Therapeutics; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Forty Seven; Financial Interests, Institutional, Research Grant: Stem CentRx; Financial Interests, Institutional, Research Grant: Onyx; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Abbott/AbbVie; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Celldex; Financial Interests, Institutional, Research Grant: Agios; Financial Interests, Institutional, Research Grant: ARMO BioSciences; Financial Interests, Institutional, Research Grant: CytomX Therapeutics; Financial Interests, Institutional, Research Grant: Nektar; Financial Interests, Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Research Grant: Merrimack; Financial Interests, Institutional, Research Grant: Tarveda Therapeutics; Financial Interests, Institutional, Research Grant: Tyrogenex; Financial Interests, Institutional, Research Grant: Oncogenex; Financial Interests, Institutional, Research Grant: Marshall Edwards; Financial Interests, Institutional, Research Grant: Pieris Pharmaceuticals; Financial Interests, Institutional, Research Grant: Mersana; Financial Interests, Institutional, Research Grant: Calithera Biosciences; Financial Interests, Institutional, Research Grant: Blueprint Medicines; Financial Interests, Institutional, Research Grant: Gritstone Oncology; Financial Interests, Institutional, Research Grant: Evelo Therapeutics; Financial Interests, Institutional, Research Grant: FORMA Therapeutics; Financial Interests, Institutional, Research Grant: Forty Seven; Financial Interests, Institutional, Research Grant: EMD Serono; Financial Interests, Institutional, Research Grant: Merus; Financial Interests, Institutional, Research Grant: Jacobio; Financial Interests, Institutional, Research Grant: eFFECTOR Therapeutics; Financial Interests, Institutional, Research Grant: Novocure; Financial Interests, Institutional, Research Grant: Sorrento Therapeutics; Financial Interests, Institutional, Research Grant: Arrys Therapeutics; Financial Interests, Institutional, Research Grant: TRACON Pharma; Financial Interests, Institutional, Research Grant: Sierra Oncology; Financial Interests, Institutional, Research Grant: Innate Pharma; Financial Interests, Institutional, Research Grant: Prelude Therapeutics; Financial Interests, Institutional, Research Grant: Arch Oncology; Financial Interests, Institutional, Research Grant: Harpoon therapeutics; Financial Interests, Institutional, Research Grant: Phoenix Biotech; Financial Interests, Institutional, Research Grant: Unum Therapeutics; Financial Interests, Institutional, Research Grant: Vyriad; Financial Interests, Institutional, Research Grant: Harpoon therapeutics; Financial Interests, Institutional, Research Grant: cyteir; Financial Interests, Institutional, Research Grant: Molecular Partners; Financial Interests, Institutional, Research Grant: Innate Pharma; Financial Interests, Institutional, Research Grant: ADC Therapeutics; Financial Interests, Institutional, Research Grant: Torque; Financial Interests, Institutional, Research Grant: Tizona Therapeutics, Inc.; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: BeiGene; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Millenium Pharamceuticals; Financial Interests, Institutional, Research Grant: ImClone Systems; Financial Interests, Institutional, Research Grant: Acerta Pharma; Financial Interests, Institutional, Research Grant: Rgenix; Financial Interests, Institutional, Research Grant: Bellicum Pharmaceuticals; Financial Interests, Institutional, Research Grant: Arcus Biosciences; Financial Interests, Institutional, Research Grant: Gossamer Bio; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Tempest Therapeutics; Financial Interests, Institutional, Research Grant: Shattuck Labs; Financial Interests, Institutional, Research Grant: Synthorx; Financial Interests, Institutional, Research Grant: Revolution Medicines; Financial Interests, Institutional, Research Grant: Bicycle Therapeutics; Financial Interests, Institutional, Research Grant: Zymeworks; Financial Interests, Institutional, Research Grant: Relay Therapeutics; Financial Interests, Institutional, Research Grant: Evelo Therapeutics; Financial Interests, Institutional, Research Grant: Scholar Rock; Financial Interests, Institutional, Research Grant: NGM Biopharmaceuticals; Financial Interests, Institutional, Research Grant: Numab; Financial Interests, Institutional, Research Grant: AtlasMedx; Financial Interests, Institutional, Research Grant: Treadwell Therapeutics. All other authors have declared no conflicts of interest.
514O - An open-label, global, first-in-human study of SKB264 in patients with locally advanced or metastatic solid tumors
- Jordi Rodon (Houston, United States of America)
Abstract
Background
SKB264 is an antibody drug conjugate (ADC) composed of an antibody targeting the trophoblast cell-surface antigen 2 (TROP2), which is overexpressed in many types of solid tumors, coupled to moderate cytotoxic belotecan-derivative through a novel linker which was designed to balance the extracellular stability and intracellular rupture. We hereby report initial results of the FIH study (NCT04152499; CTR20201069).
Methods
Patients (pts) aged ≥18 with unresectable solid tumors refractory to/relapsed from standard treatment with measurable disease per RECIST 1.1 will be enrolled and receive SKB264 Q2W every 4 weeks as monotherapy. The objectives are to determine the safety, tolerability, pharmacokinetics (PK) and antitumor activity of SKB264.
Results
The dose escalation study is still ongoing. As of March 15, 2021, 18 pts were enrolled in 3 dose levels (2, 4 and 6 mg/kg). Treatment emergent adverse events (TEAEs) regardless of causality were reported in 18 of 18 pts, the most common TEAEs were Grade (G) 1-2 nausea (72.2%) and alopecia (66.7%). The most common≥G3 TEAEs were neutrophil count decreased (27.8%), white blood cell count decreased (22.2%), and anemia (16.7%). The above ≥G3 AEs were recovered after corresponding treatment. No TEAE led to death. The PK results suggest that exposure of SKB264 increased proportionally with dose, and no accumulation observed after multiple doses. The half-lives of SKB264 and free payload are approximately 36 hours and 49 hours respectively, which support the dose regimen of Q2W. Serum free payload was about 6% and 5% of total SKB264 (ADC) Cmax and AUC respectively in Cycle 1, indicated the stable novel linker of SKB264 in the serum. A total of 17 pts had undergone at least one tumor assessment, and preliminary efficacy was observed in all dose levels from 2 to 6 mg/kg. Six patients had Partial Response per RECIST 1.1: 2 triple-negative breast cancer (40%, 2/5), 2 ovarian cancer (40%, 2/5), 1 HER2+breast cancer (100%, 1/1), and 1 gastric adenocarcinoma (100%, 1/1). The Overall Response Rate (ORR) is 35.3% (6/17) and the Disease Control Rate (DCR) is 70.6% (12/17).
Conclusions
SKB264 has demonstrated encouraging safety and antitumor activity. Study continues to identify dose(s) of SKB264.
Clinical trial identification
NCT04152499 November 5, 2019.
Legal entity responsible for the study
Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.
Funding
Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.
Invited Discussant 513O and 514O
- Elena Garralda (Barcelona, Spain)
Q&A and live discussion
- Elena Garralda (Barcelona, Spain)