Abstract 60P
Background
SG, a Trop-2–directed antibody-drug conjugate, has demonstrated activity and manageable safety in heavily pretreated patients with mNSCLC. EVOKE-02 (NCT05186974) is an open-label, multicohort phase II study evaluating SG + pembro ± a platinum agent in 1L mNSCLC. Here we report results by histology (squamous vs nonsquamous) in patients treated with SG + pembro in Cohorts A and B of EVOKE-02.
Methods
Patients aged ≥ 18 years, with no prior systemic treatment for mNSCLC, no actionable genomic alterations, and an ECOG PS of ≤ 1 were enrolled into Cohort A (programmed death [ligand] 1 [PD-L1] tumor proportion score [TPS] ≥ 50%) or B (PD-L1 TPS < 50%). PD-L1 status, if not already known, was determined locally or at the central laboratory using the 22C3 assay prior to enrollment. Patients received SG 10 mg/kg on Days 1 and 8 + pembro 200 mg on Day 1 of a 21-day cycle. The primary end point is objective response rate (ORR; per RECIST v1.1); secondary end points include progression-free survival, overall survival, duration of response (DOR), disease control rate (DCR), and safety.
Results
As of June 16, 2023, 30 patients in Cohort A and 33 in Cohort B were enrolled. In Cohort A (PD-L1 TPS ≥ 50%), the ORR by investigator assessment was 73% (8/11) in efficacy-evaluable patients (those with ≥ 13 weeks of follow-up) with squamous mNSCLC and 67% (12/18) in patients with nonsquamous mNSCLC; in Cohort B (PD-L1 TPS < 50%), it was 54% (7/13) and 37% (7/19), respectively (Table). Median DOR was not reached in either cohort. In the safety population (N = 63), any-grade treatment-emergent adverse events (TEAEs) were reported in 63 patients (100%; grade ≥ 3, 70%). Table: 60P
| Efficacy by investigator assessment | Squamous mNSCLC | Nonsquamous mNSCLC | ||
| Cohort APD-L1 TPS≥ 50% (n = 11) | Cohort BPD-L1 TPS< 50% (n = 13) | Cohort APD-L1 TPS≥ 50% (n = 18) | Cohort BPD-L1 TPS< 50% (n = 19) | |
| ORR,a n (%) [95% CI] | 8 (73) [39-94] | 7 (54) [25-81] | 12 (67) [41-87] | 7 (37) [16-62] |
| Best overall response,a n (%) | ||||
| PR | 8 (73) | 7 (54) | 12 (67) | 7 (37) |
| Confirmed PR | 7 (64) | 6 (46) | 11 (61) | 6 (32) |
| SD | 1 (9) | 4 (31) | 4 (22) | 7 (37) |
| PD | 2 (18) | 0 | 1 (6) | 2 (11) |
| Not assessed | 0 | 2 (15) | 1 (6) | 3 (16) |
| DCR,b n (%) [95% CI] | 9 (82) [48-98] | 11 (85) [55-98] | 16 (89) [65-99] | 14 (74) [49-91] |
PD, progressive disease; PR, partial response; SD, stable disease.
aIncludes confirmed and unconfirmed responses.
bComplete response + PR + SD ≥ 6 weeks.
Conclusions
In EVOKE-02, SG + pembro showed promising activity regardless of histology (squamous and nonsquamous) in previously untreated mNSCLC. The safety profile was manageable and consistent with the known safety profile of each agent.
Clinical trial identification
NCT05186974.
Editorial acknowledgement
Medical writing and editorial support was provided by Sonal Joshi, PhD, of Parexel, and funded by Gilead Sciences, Inc. This study is in collaboration with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Legal entity responsible for the study
Gilead Sciences, Inc.
Funding
Gilead Sciences, Inc.
Disclosure
F. Cappuzzo: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Mirati, PharmaMar, Novocure, OSE, GALECTO and MSD; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Mirati, Novocure, OSE, andMSD. J. Patel: Financial Interests, Personal, Advisory Board: AbbVie, AnHeart, AstraZeneca, BMS, Daiichi Sankyo, Gilead, Guardant, Sanofi, Takeda; Financial Interests, Personal, Other, travel: Tempus; Financial Interests, Personal, Invited Speaker, travel: Daiichi Sankyo. B.C. Cho: Financial Interests, Personal, Other, Consulting role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Medpacto, Blueprint medicines, RandBio, Hanmi, GC Cell, Gilead, Ridgeline Discovery GmbH; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc, J INTS Bio, Therapex Co., Ltd, Gilead, Amgen, AstraZeneca, Regeneron, Seagen, Samsung Bioepis; Financial Interests, Personal, Member of Board of Directors: Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Full or part-time Employment: Yonsei University Health System; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Royalties: Champions Oncology, Crown Bioscience, Imagen, PearlRiver Bio GmbH, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: CHA Bundang Medical Center, MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, Gradiant Bioconvergence, Therapex, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Oncology, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, JINTSbio, Hanmi, Daewoong Pharmaceutical Co., Ltd., Vertical Bio AG, Korea Institute of Oriental Medicine, National Research Foundation of Korea, KHIDI; Other, Personal, Other, Founder: DAAN Biotherapeutics; Other, Personal, : ASCO. D. Vicente Baz: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD Oncology, Pfizer, Roche/Genentech. J. Fuentes Pradera: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, MSD, Takeda, Sanofi; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Gilead, Roche, Daiichi, Bioatla. J. Neal: Financial Interests, Personal, Other, Honoraria: CME Matters, Clinical Care Options CME, Research to Practice CME, Medscape CME, Biomedical Learning Institute CME, MLI Peerview CME, Prime Oncology CME, Projects in Knowledge, Rockpointe CME, MJH Life Sciences CME, Medical Educator Consortium, HMP Education; Financial Interests, Personal, Advisory Role: AstraZeneca, Genentech/Roche, Exelixis, Takeda Pharmaceuticals, Eli Lilly and Company, Amgen, Iovance Biotherapeutics, Blueprint Pharmaceuticals, Regeneron Pharmaceuticals, Natera, Sanofi/Regeneron, D2G Oncology, Surface Oncology, Turning Point Therapeutics, Mirati Therapeutics, Gilead Sciences, AbbVie, Summit Therapeutics, Novartis, Novocure, Janssen Oncology, Anheart Therapeutics; Financial Interests, Institutional, Research Grant: Genentech/Roche, Merck, Novartis, Boehringer Ingelheim, Exelixis, Nektar Therapeutics, Takeda Pharmaceuticals, Adaptimmune, GSK, Janssen, AbbVie, Novocure; Financial Interests, Personal, Other, Royalties: Up to date - Royalties . E.B. Garon: Financial Interests, Personal, Advisory Board: Novartis, BMS, EMD Serono, Regeneron, Sanofi, Gilead, Eli Lilly, Zymeworks, AstraZeneca, AbbVie, Sensei, Seagan, Arcus, Summit, Synthekine, BridgeBio, Atreca, Sumitomo, Merus, Hookipa, LianBio; Financial Interests, Personal, Other, DSMB: Nuvalent; Financial Interests, Personal, Other, Independent Medical Education: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Novartis, Merck, EMD Serono, Eli Lilly, Genentech, Iovance, Mirati, AstraZeneca, BMS, ABL Bio, Daiichi Sankyo Sanko, Prelude, Arrivent, Regeneron, Synthekine, Gilead; Non-Financial Interests, Personal, Advisory Role, Scientific Advisory Board: Lungevity. S. Mekan: Financial Interests, Institutional, Full or part-time Employment: Gilead Sciences. F. Safavi: Financial Interests, Personal, Full or part-time Employment: Gilead Sciences, Inc. N. Fernando: Financial Interests, Personal, Stocks/Shares: Gilead Sciences, Inc.; Non-Financial Interests, Personal, Advisory Board, Safety Review Meetings: Gilead Sciences, Inc. M. Chisamore: Financial Interests, Institutional, Stocks/Shares: Merck & Co. Inc; Financial Interests, Institutional, Full or part-time Employment: Merck & Co. Inc. M. Reck: Financial Interests, Personal, Other, Consulting: Amgen, AstraZeneca, Boehringer Ingelheim, BeiGene, Daiichi Sankyo, Lilly, Merck, Mirati Therapeutics, MSD Oncology, Novartis, Pfizer, Roche, Regeneron, Sanofi, Janssen, Bristol Myers Squibb, Regeneron; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, AstraZeneca, Boehringer Ingelheim, Amgen, Celgene, Lilly, Merck Serono, Mirati Therapeutics, MSD Oncology, Novartis, Pfizer, Roche, Sanofi, Janssen; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Jannsen, Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, BMS, Lilly, Merck, MSD, Mirati, Novartis, GSK, Pfizer, Roche, Regeneron, Sanofi, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Sanofi. All other authors have declared no conflicts of interest.