1398TiP - Be6A Lung-01, a phase III study of sigvotatug vedotin (SV), an investigational antibody-drug conjugate (ADC) versus docetaxel in patients (pts) with previously treated non-small cell lung cancer (NSCLC)

Background

Integrin beta-6 (IB6) expression is correlated with poor outcomes in several cancers, including NSCLC, and >90% of NSCLC tumors express IB6.^1-3 SV (formerly known as SGN-B6A) is an IB6-directed ADC that demonstrated encouraging activity in heavily pretreated pts with NSCLC and other solid tumors.^4,5 In NSCLC, second line or subsequent treatment options offer limited benefit for pts whose disease has progressed after treatment with programmed cell death-ligand 1 (PD-[L]1) inhibitors, platinum-based chemotherapy, and/or targeted therapy. High unmet needs remain for pts with previously treated NSCLC.

Trial design

Be6A Lung-01 (NCT06012435) is a ph 3, open label, global study evaluating the efficacy and safety of SV compared with docetaxel in pts with locally advanced, unresectable, or metastatic nonsquamous NSCLC. Pts must have experienced disease progression during or after treatment with PD-(L)1 inhibitors, platinum-based chemotherapy, or targeted treatment regimen(s) for known actionable genomic alterations (AGAs), where applicable. Pts must not have received prior treatment with antimicrotubule agents, and not more than 1 prior line of cytotoxic chemotherapy. Approximately 600 pts will be randomized in a 1:1 ratio to receive SV 1.8 mg/kg using their Adjusted Ideal Body Weight (AiBW) intravenously (IV) on Days 1 and 15 of a 28-day cycle (Q2W) or docetaxel 75 mg/m² IV on Day 1 of a 21-day cycle (Q3W). Randomization is stratified based on ECOG PS, AGAs, and regions. Pts must have ECOG PS of 0 or 1, with adequate organ function. The primary endpoints are OS and confirmed ORR by Blinded Independent Central Review (BICR) per RECIST v1.1. The key secondary endpoint is PFS by BICR per RECIST v1.1; other secondary endpoints include confirmed ORR, PFS by investigator, DOR by BICR and investigator per RECIST v1.1, safety, and patient-reported outcomes. Enrollment has begun in the US and the EU and is planned for other regions, including APAC and LATAM. References: 1. Li 2020; 2. Elayadi 2007; 3. Pfizer internal data on file; 4. Hollebecque SITC 2022; 5. Hollebecque ASCO 2023.

Clinical trial identification

NCT06012435.

Editorial acknowledgement

Editorial support was provided by Gary Dever, PhD, CMPP of Engage Scientific Solutions and was funded by Pfizer.

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc.

Disclosure

S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GSK, Gilead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure; Financial Interests, Institutional, Invited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, eCancer, Boehringer Ingelheim, BMS, AstraZeneca, OncologyEducation, RMEI, Mirati; Financial Interests, Personal, Other, Associate Editor Annals of Oncology and Deputy Editor Lung Cancer: Elsevier; Financial Interests, Institutional, Advisory Board, Permanent independent scientific advisor: HUTCHMED; Financial Interests, Institutional, Member of Board of Directors, Swiss network of pharmacies: Galenica; Financial Interests, Institutional, Coordinating PI, MERMAID-1: AstraZeneca; Financial Interests, Institutional, Steering Committee Member, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca; Financial Interests, Institutional, Steering Committee Member, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS; Financial Interests, Institutional, Steering Committee Member, RELATIVITY 095: BMS; Financial Interests, Institutional, Steering Committee Member, BGB-A317-A1217-301/AdvanTIG-301: BeiGene; Financial Interests, Institutional, Trial Chair, Clinical Trial Chair ZEAL-1: GSK; Financial Interests, Institutional, Steering Committee Member, Clinical Trial steering Committee PEARLS, MK-7684A: MSD; Financial Interests, Institutional, Steering Committee Member, Clinical Trial Steering Committee SAPPHIRE: Mirati; Financial Interests, Institutional, Steering Committee Member, LAGOON: PharmaMar; Financial Interests, Institutional, Steering Committee Member, phase 1/2 trials: Phosplatin Therapeutics; Financial Interests, Institutional, Trial Chair, Clinical Trial Chair Skyscraper-01; chair ALEX; steering committee BFAST; steering committee BEAT-Meso; steering committee ImPower-030, IMforte: Roche/Genentech; Financial Interests, Institutional, Steering Committee Member, Phase 2 Inupadenant with chemo: iTeos; Non-Financial Interests, Officer, ESMO President 2020-2022: ESMO; Non-Financial Interests, Officer, Council Member & Scientific Committee Chair: ETOP/IBCSG Partners; Non-Financial Interests, Officer, Vice-President Lung Group: SAKK; Non-Financial Interests, Other, Involved in Swiss politics: Swiss Political Activities; Non-Financial Interests, Officer, President and Council Member: Ballet Béjart Lausanne Foundation; Non-Financial Interests, Principal Investigator, Involved in academic trials: ETOP / EORTC / SAKK; Non-Financial Interests, Member: Association of Swiss Physicians FMH (CH), ASCO, AACR, IASLC; Non-Financial Interests, Leadership Role, ESMO President: ESMO; Non-Financial Interests, Member, Vice-President Lung Group: SAKK; Non-Financial Interests, Leadership Role, Vice -President: SAMO; Non-Financial Interests, Member, Association of Swiss interns and residents: ASMAC/VSAO. M.L. Cheng: Financial Interests, Institutional, Advisory Role: Janssen, Mirati Therapeutics, Pfizer; Financial Interests, Institutional, Research Funding: Palleon Pharmaceuticals. D. Planchard: Financial Interests, Personal, Advisory Role: Prime Oncology, PeerVoice; Financial Interests, Institutional, Advisory Role: AbbVie, ArriVent, AZ, BeiGene, BI, BMS, Celgene, Daiichi Sankyo, Janssen, MedImmune, Mirati, MSD, Novartis, Samsung, Seagen, Pfizer, Pierre Fabre, Roche, Takeda; Financial Interests, Institutional, Research Funding: AbbVie, ArriVent, AZ/MedImmune, BI, BMS, Daiichi Sankyo, Janssen, Lilly, Merck, Mirati, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi/Aventis, Seagen, Taiho Pharmaceutical, Takeda. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, BMS, Boehringer-Ingelheim, Lilly, MSD, Merck, Novartis, Regeneron, Roche, Sanofi, GSK, Pfizer; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, BioNTech, Boehringer-Ingelheim, Daiichi Sankyo, Gilead, MSD, Mirati, Pfizer, Regeneron, Roche, Sanofi, GSK, Lilly; Financial Interests, Personal, Other, Member of DMSB: Daiichi Sankyo; Financial Interests, Personal, Coordinating PI: AstraZeneca; Financial Interests, Institutional, Steering Committee Member: Amgen, Boehringer-Ingelheim, BeiGene, Daiichi Sankyo, GSK, BMS, Lilly, MSD, Regeneron, Roche; Financial Interests, Institutional, Local PI: Pfizer Seagen. R.A. Soo: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BMS, Lily, Merck, Novartis, Pfizer, Roche, Taiho, Takeda, Yuhan, Janssen, Merck Serono, Puma Biotech, Thermo Fisher; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim; Financial Interests, Personal, Research Grant: Pfizer. Y. Zhu, E. Kim: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. N. Yamamoto: Financial Interests, Institutional, Research Funding: AbbVie, Astellas, AZ, Bayer, BI, BMS, Carna Biosciences, Chiome Bioscience, Chugai, Cmic, Daiichi Sankyo, Eisai, Eli Lilly, Genmab, GSK, InventisBio, Janssen, Kaken, Kyowa Kirin, Merck, MSD, Novartis, ONO, Otsuka, Pfizer, Rakuten Medical, Shionogi, Sumitomo Pharma, Taiho, Takeda, Toray; Financial Interests, Personal, Advisory Role: BI, Cmic, Chugai, Daiichi Sankyo, Eisai, Healios, Merck, Takeda. All other authors have declared no conflicts of interest.