22O - Association of biomarkers with response to coformulated vibostolimab/pembrolizumab (vibo/pembro) in metastatic cervical cancer (CC): Exploratory analysis from the phase II KEYVIBE-005 study

Background

In the multicohort KEYVIBE-005 study (NCT05007106), vibo/pembro (n = 85) showed antitumor activity similar to pembro (n = 84; ORR, 20.0% vs 15.5%) with a manageable safety profile in patients (pts) with previously untreated metastatic CC with PD-L1 CPS ≥1. We evaluated the association between biomarkers and response to treatment in this cohort.

Methods

Using tumor samples, expression of TIGIT on immune cells (clone SP410, FLA assay) and PD-L1 CPS (PD-L1 22C3 pharmDx) were evaluated by IHC, T-cell–inflamed gene expression profile (Tcell_infGEP) by NanoString, and TMB by WES. ORR and PFS were evaluated. Significance of continuous biomarkers was prespecified at 0.05 for 1-sided P values from logistic (ORR) and Cox proportional hazard (PFS) regression. ctDNA was isolated from pretreatment plasma samples collected on day 1 at cycle 1 (C1), C2, and C3 and sequenced using a personalized tumor-informed assay (Invitae PCM); quantity was expressed as maximum somatic allele frequency (MSAF).

Results

The association of biomarkers with ORR and PFS is reported in the table. The AUROCs (95% CI) for discriminating response to vibo/pembro were as follows: TIGIT, 0.64 (0.48-0.80); PD-L1, 0.72 (0.61-0.83); Tcell_infGEP, 0.71 (0.56-0.86); and TMB, 0.74 (0.58-0.91). The AUROCs (95% CI) for discriminating response to pembro were as follows: TIGIT, 0.63 (0.47-0.79); PD-L1, 0.68 (0.50-0.86); Tcell_infGEP, 0.65 (0.46-0.84); and TMB, 0.71 (0.46-0.95). Median ctDNA MSAF was reduced by 21% at C2 and by 32% at C3 with vibo/pembro (from C1) compared with 4% and 6% reductions, respectively, with pembro.Table: 22O

P values of the association analysis between biomarkers and clinical outcomes

Conclusions

In pts with CC with PD-L1 CPS ≥1, all biomarkers trended towards a positive association with response to vibo/pembro; the strongest associations were observed for PD-L1 and Tcell_infGEP. Trends towards larger ctDNA decreases were observed with vibo/pembro vs pembro.

Clinical trial identification

NCT05007106 (study start date: 2021-09-16).

Editorial acknowledgment

Medical writing and/or editorial assistance was provided by Shanel Dhani, PhD, Mehak Aggarwal, PharmD, and Holly C. Cappelli, PhD, CMPP, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, 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. Le Tourneau: Financial Interests, Personal, Advisory Board: BMS, MSD, Merck Serono, Nanobiotix, Roche, Rakuten, Seattle Genetics, GSK, Celgene, ALX Oncology, Exscientia. C.I. Rojas: Financial Interests, Personal, Advisory Board: BMS, Roche, MSD, Pfizer, Sanofi; Financial Interests, Personal, Invited Speaker: BMS, MSD, AstraZeneca, Knight, Pfizer; Financial Interests, Personal, Member of Board of Directors: Bradford Hill. A. Leary: Financial Interests, Personal, Advisory Board: Zentalis; Financial Interests, Personal, Invited Speaker, Educational: GSK, Medscape, Onko+; Financial Interests, Institutional, Other, Steering committee: MSD; Financial Interests, Institutional, Advisory Board: GSK, AstraZeneca, Clovis, Ability Pharma, MSD, Merck Serono, Apmonia, Blueprint; Financial Interests, Institutional, Invited Speaker, Educational: Kephren publishing; Financial Interests, Institutional, Other, Consultancy: Orion; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Clovis; Financial Interests, Personal, Other, Consultancy: GLG; Financial Interests, Institutional, Other, consultancy: OWKIN; Financial Interests, Institutional, Research Grant, PI translational research: ARCAGY-GINECO, Sanofi, AstraZeneca; Financial Interests, Institutional, Funding, CI clinical trial: AstraZeneca; Financial Interests, Institutional, Research Grant, Int CI clinical trial: OSE immuno; Financial Interests, Institutional, Funding, PI clinical trial: Agenus, BMS, Iovance, GSK; Financial Interests, Institutional, Funding, PI 5 clinical trials: Roche; Financial Interests, Institutional, Funding, PI 2 clinical trials: AstraZeneca; Financial Interests, Institutional, Funding, PI 3 clinical trials and steering committee: MSD; Non-Financial Interests, Institutional, Other, Academic research project: Owkin, LXRepair; Non-Financial Interests, Personal, Proprietary Information, IDMC member: Clovis; Non-Financial Interests, Personal, Proprietary Information, IDMC chair: Pfizer; Non-Financial Interests, Personal, Member: GCIG. K. Yonemori: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, Sanofi, Genmab, Gilead, 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, Janssen, 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. I. Lugowska: Financial Interests, Personal, Invited Speaker: Roche, ESMO; Financial Interests, Institutional, Other, Research grants: Roche; Financial Interests, Institutional, Other, Research grant: Agenus; Financial Interests, Personal and Institutional, Invited Speaker: MSD, Roche, BMS, Janssen, AstraZeneca, Amgen, RyVu, Incyte, Siropa, Mennarini, Celon, Pfizer, Agenus, Rhizen; Non-Financial Interests, Personal, Project Lead: MSCI; Non-Financial Interests, Personal, Other, Board Member: OECI; Other, Personal, Other, Robert Lugowski (my husband) co-ownership: Clininote. D. Tosi: Financial Interests, Institutional, Advisory Board: Mabqi, Vertical; Financial Interests, Institutional, Invited Speaker, preclinical research grant: Ipsen, Bayer; Financial Interests, Institutional, Invited Speaker, Compensations for local PI role in clinical trials: Several pharmaceutical companies; Non-Financial Interests, Personal, Leadership Role: Fondazione Gianni Bonadonna; Non-Financial Interests, Personal, Advisory Role: CyteaBio, Phost'in, Revolution Medicines, Brenus Pharma, Italian Ministry of health, Cancéropôle PACA, Qu Biologics; Non-Financial Interests, Institutional, Product Samples, drug for research purposes: Ipsen, Bayer; Non-Financial Interests, Personal, Other, support for participation to scientific meetings: Several pharmaceuticals companies. F. Ghiringhelli: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Amgen, Merck Serono, MSD. C. Caglevic: Financial Interests, Personal, Research Grant: Principal/ Sub investigator for: MSD, AstraZeneca, Roche, Astellas Pharma, BMS, GSK, Athenex, Sanofi, AbbVie, Amgen, Bayer Healthcare Pharmaceuticals, Biontech, Daiichi Sankyo INC, Exelixis, Novartis, F. Hoffmann LaRoche, PharmaMar, Zymeworks, Cogent Biosciences, . R. Perets: Financial Interests, Personal, Other, Consultant: Galmed Therapeutics, Gilboa Therapeutics, 1E Therapeutics; Financial Interests, Institutional, Invited Speaker: Janssen, MSD, BMS, Genentech, Biomica, Amgen, AbbVie, Ammune; Non-Financial Interests, Institutional, Product Samples, Antibody for research: AbbVie. S.Y. Rha: Financial Interests, Personal, Advisory Board: Indivumed, Amgen, LG biochemical, Astellas; Financial Interests, Personal, Invited Speaker: MSD, Eli Lilly, Daiichi Sankyo, Amgen; Financial Interests, Institutional, Funding: MSD, Eli Lilly; Financial Interests, Institutional, Research Grant: BMS, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Indivumed, AstraZeneca; Financial Interests, Personal, Other, Drug supply for clinical trial: Merck; Financial Interests, Institutional, Invited Speaker, Drug supply for clinical trial: MSD; Financial Interests, Institutional, Invited Speaker, Drug supply for clinical trial: zy, Meworks; Financial Interests, Institutional, Invited Speaker, Drug supply for clinical trial: BeiGene; Financial Interests, Personal, Invited Speaker, Drug supply for clinical trial: Incyte. T. Doi: Financial Interests, Personal, Other, Advisory Role: Noil-Immune Biotech, Oncolys BioPharma, Boehringer Ingelheim, A2 Healthcare, Nano Carrier, PRA Health Sciences, KAKEN Pharma, Chugai Pharma, Sumitomo Pharma, SHIONOGI, Otsuka Pharma, Takeda, Kyowa Kirin, Rakuten Medical, Gilead; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Taiho, MSD, AbbVie, Eisai, Pfizer, BMS, Janssen Pharma, Daiichi Sankyo, Chugai Pharma, Boehringer Ingelheim, PRA Health Sciences, Amgen, GSK, SHIONOGI, RIN Institute, ONO Pharma. Y. Zhang, T. Keenan, E. Dettman: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. G. Akturk: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Invited Speaker: Merck & Co., Inc.. C.E. Pena. Y. Chen: Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.; Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.. All other authors have declared no conflicts of interest.