Abstract 401P
Background
The checkpoint inhibitor TIGIT is coexpressed with PD-L1 in EC, and higher expression of TIGIT and PD-L1 is associated with a worse prognosis. Dual blockade of TIGIT and PD-(L)1 may be an effective therapeutic strategy. We present results from cohort E of the open-label phase 2 KEYVIBE-005 study (NCT05007106), which evaluated first-line vibo/pembro (anti-TIGIT/anti–PD-1) + chemo in patients (pts) with advanced EC.
Methods
Eligible pts had unresectable locally recurrent or metastatic adenocarcinoma or squamous cell carcinoma (SCC) of the esophagus or Siewert type 1 adenocarcinoma of the GEJ and an ECOG PS of 0 or 1 and had not received prior treatment. The study comprised a safety lead-in to identify the recommended phase 2 dose (RP2D) followed by a dose-expansion phase of ≤2 years. The starting dose was vibo 200 mg/pembro 200 mg Q3W + 5-FU 800 mg/m2/day for 5 days + cisplatin 80 mg/m2 Q3W, with dose reduction of 5-FU and cisplatin permitted per a modified toxicity probability interval design. The primary end point was ORR per RECIST v1.1 by investigator review. Secondary end points included DOR and PFS per RECIST v1.1, OS, and safety.
Results
A total of 40 pts were enrolled. Median age was 60.5 years, 88% of pts were male, 65% had an ECOG PS of 1, 78% had SCC, 20% had adenocarcinoma, and 3% had poorly differentiated adenocarcinoma. At the data cutoff (Oct 24, 2023), median follow-up was 16.6 mo (range, 10.6-24.6). One of 10 pts (10%) in the safety lead-in experienced a dose-limiting toxicity (grade 3 stomatitis); the RP2D was identified as vibo 200 mg/pembro 200 mg Q3W + 5-FU 4000 mg/m2 + cisplatin 80 mg/m2 Q3W. At data cutoff, 26 pts (65%) had discontinued treatment. Efficacy and safety data are reported in the table. Table: 401P
Efficacy and safety data
| ORR: all, n/N (%) | 21/40 (53) |
| ORR: SCC, n/N (%) | 16/31 (52) |
| ORR: adenocarcinoma, a n/N (%) | 4/8 (50) |
| Median DOR, mo (95% CI) | 13.9 (7.9-not reached) |
| DOR ≥12 mo, % | 61 |
| Median PFS, mo (95% CI) | 10.4 (6.4-18.0) |
| 12-mo PFS, % | 43 |
| Median OS, mo (95% CI) | 18.0 (10.7-not reached) |
| 12-mo OS, % | 67 |
| TRAE: Any grade, n (%) | 38 (95) |
| TRAE: Grade 3-5, b n (%) | 29 (73) |
| Most common grade 3-5 TRAEs (≥20%): Neutropenia (28%) and anemia (20%) | |
| Immune-mediated AEs or infusion reactions: Any grade, n (%) | 15 (38) |
| Immune-mediated AEs or infusion reactions: Grade 3-5, n (%) | 7 (18) |
aOne pt with poorly differentiated adenocarcinoma had a confirmed response
bOne grade 5 event (pneumonitis)
Conclusions
Vibo/pembro + 5-FU + cisplatin had promising antitumor activity and manageable safety in pts with previously untreated advanced EC.
Clinical trial identification
NCT05007106; study start: 2021-09-16.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Shanel Dhani, PhD, and Holly C. Cappelli, PhD, CMPP, of ApotheCom (Yardley, PA, USA).
Legal entity responsible for the study
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Funding
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Disclosure
C. Hsu: Financial Interests, Personal and Institutional, Advisory Board: BMS, Ono Pharmaceuticals, Roche, AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: BMS, Ono Pharmaceuticals AstraZeneca; Financial Interests, Personal and Institutional, Principal Investigator: BMS, Ono Pharmaceuticals, Merck Sharp & Dohme, Roche, BeiGene, NGM Biopharmaceuticals, Surface Oncology, Ipsen, Taiho Pharmaceuticals, AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker: BMS, Ono Pharmaceuticals, Merck Sharp & Dohme, Roche; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Institutional, Research Grant: BeiGene, NGM Pharmaceuticals, Surface Oncology, Ipsen, Taiho Pharmaceuticals; Financial Interests, Institutional, Principal Investigator: BeiGene, NGM Pharmaceuticals, Surface Oncology, Ipsen, Taiho Pharmaceuticals,. R. Dziadziuszko: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Pfizer, Takeda, MSD, Bristol Myers Squibb, Bayer; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Expert Testimony: Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Roche, AstraZeneca, MSD, Amgen, Celon Pharma, Pfizer, Novartis, Bristol Myers Squibb, Eli Lilly, Loxo; Financial Interests, Personal and Institutional, Other, Sub investigator and ad hoc Consultant: PDC*line Pharma; Financial Interests, Invited Speaker: OSE Immunotherapeutics; Non-Financial Interests, Institutional, Product Samples: Novartis, Pfizer, AstraZeneca, Roche. M. Gil Martín: Financial Interests, Personal, Invited Speaker: MSD, GSK, Clovis. P. Cassier: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: Roche, Amgen, Boehringer Ingelheim; Financial Interests, Personal, Other, Advisor: OSE immunotherapeutics; Financial Interests, Institutional, Invited Speaker: AbbVie, Amgen, Blueprint, Boehringer Ingelheim, Bristol Meyer Squibb, Exelixis, GSK, Incyte, Janssen, Loxo/Eli Lilly, Novartis, Roche, Taiho, Toray Industries, Transgene; Non-Financial Interests, Institutional, Product Samples: Plexxikon, Novartis, MSD, AstraZeneca, GSK. S. Im: Financial Interests, Personal, Advisory Board, no payment: AstraZeneca, Novartis, Eisai, Roche, Hanmi, Pfizer, Lilly, MSD, GSK, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Bertis; Financial Interests, Personal, Advisory Board: Idience; Financial Interests, Institutional, Research Grant: AstraZeneca, Pfizer, Roche, Eisai, Dae Woong; Financial Interests, Institutional, Invited Speaker, Clinical Trial Budget: AstraZeneca, Eisai, Hanmi, Novartis, Roche, Pfizer, Daiichi Sankyo, MSD, Lilly; Financial Interests, Institutional, Research Grant, Clinical Trial Budget: Boryung Pharm. S. Kim: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Lilly, DaeHwa Pharma, ISU Abx, Daiichi Sankyo, BeiGene, Samsung Bioepics, OBI Pharma; Financial Interests, Personal, Invited Speaker: Legochem Bioscience; Financial Interests, Personal, Ownership Interest: Genopeaks; Financial Interests, Institutional, Research Grant: Novartis, Sanofi-Genzyme, DongKook Pharm Co. T. Kudo: Financial Interests, Personal, Invited Speaker: Merck Biopharma Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bristol Myers Squibb K.K., MSD Co., Ltd., Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Advisory Board: Daiichi Sankyo Co., Ltd.; Financial Interests, Institutional, Invited Speaker: Astellas Pharma Inc., Novartis Pharma K.K., Amgen inc., ONO Pharmaceutical Co., Ltd., MSD Co., Ltd., AstraZeneca K.K., Incyte Biosciences Japan G.K.; Financial Interests, Institutional, Research Grant: Pfizer Inc. S. Ochsenreither: Financial Interests, Personal, Advisory Board: MSD, BMS, Janssen, Ipsen, Immunocore, Genemab, Pfizer; Financial Interests, Personal, Invited Speaker: MSD, Merck, Immunocore, Janssen; Financial Interests, Personal, Other, Support for travel/meeting: Janssen, Pfizer; Financial Interests, Personal, Invited Speaker, Patent of T-cell therapy target: Fred Hutchinson cancer Research Center. M.A.N. Sendur: Financial Interests, Personal, Advisory Board: BMS, Pfizer, Takeda, Roche, Astellas; Financial Interests, Personal, Invited Speaker: Astellas, Pfizer, BMS, MSD, Roche. K. Yonemori: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, Sanofi, Genmab, Gliad, OncoXerna, Takeda, Novartis, MSD; Financial Interests, Personal, Invited Speaker: Pfizer, Eisai, AstraZeneca, Eli Lilly, Takeda, Chugai, Fuji Film Pharma, PDR Pharma, MSD, Ono, BMS, Boehringer Ingelheim, Daiichi Sankyo, Bayer, Jansen, Sanofi; Financial Interests, Institutional, Invited Speaker: MSD, Daiichi Sankyo, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seagen, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirrin, Nihon Kayaku, Haihe. C.I. Rojas: Financial Interests, Personal, Advisory Board: BMS, Roche, Roche, MSD, Pfizer, Sanofi; Financial Interests, Personal, Invited Speaker: BMS, MSD, AstraZeneca, Knight, Pfizer; Financial Interests, Personal, Member of Board of Directors: Bradford Hill. Q. Liu, T. Keenan, J. Healy: Financial Interests, Personal, Full or part-time Employment, Full Time: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. M. Kwiatkowski: Financial Interests, Personal, Invited Speaker: Janssen Cilag, Novartis, Roche; Non-Financial Interests, Principal Investigator, Clinical Trials: MSD, BMS; Non-Financial Interests, Principal Investigator, Clinical trials: AstraZeneca, Roche, Hengrui, Janssen Cilag, BeiGene, Shanghai Jinshu, Bayer. All other authors have declared no conflicts of interest.