vibostolimab (MK-7684)

P1/2, N=450, Recruiting, Merck Sharp & Dohme LLC | Active, not recruiting --> Recruiting

Background In the multicohort phase 2 KEYVIBE-005 study (NCT05007106), the antitumor activity of vibostolimab (anti-T-cell immunoreceptor with Ig and ITIM domains [TIGIT]) coformulated with pembrolizumab (anti–PD-1; vibostolimab/pembrolizumab) was demonstrated in patients with previously treated advanced mismatch repair–deficient (dMMR) endometrial cancer (cohort B1; n = 40; ORR, 64%) and in patients with previously untreated advanced esophageal cancer treated with vibostolimab/pembrolizumab plus 5-fluorouracil and cisplatin (cohort E; n = 40; ORR, 53%). Ethics Approval The study protocol and all amendments were approved by the institutional review board or ethics committee at each institution. Consent All patients provided written informed consent.

P1/2, N=450, Active, not recruiting, Merck Sharp & Dohme LLC | Phase classification: P2 --> P1/2

These studies will also evaluate coformulated immunotherapy addressing issues that occur with the sequential administration of immunotherapy. The KEYVIBE program will provide further insight into the clinical utility of vibostolimab-based therapy across multiple indications and various stages of disease.

P1, N=470, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

P1, N=492, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Oct 2024 --> Aug 2024 | Trial primary completion date: Oct 2024 --> Aug 2024

P2, N=360, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Feb 2032 --> Feb 2039 | Trial primary completion date: Feb 2032 --> Feb 2039

P1/2, N=200, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

P1/2, N=90, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

Enrollment is ongoing in Asia, Australia, Europe, North America, and South America. Clinical trial information: NCT02625961.

P2, N=360, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

In addition, we designed a single-chain variable fragment derived from the clinically tested monoclonal antibody Vibostolimab targeting TIGIT, and assessed its performance alongside the nanobodies...The excellent affinity, high specificity and rapid on-target uptake in mice bearing TIGIT- overexpressing tumors showed the promising diagnostic potential of nanobodies to noninvasively image high TIGIT expression within the tumor. These findings hold promise for clinical translation to aid patient selection and improve therapy response.

Here we describe the design and rationale for the open-label, randomized, phase II KEYSTEP-008 trial, which will evaluate the efficacy and safety of pembrolizumab-based combination therapy compared with pembrolizumab monotherapy in chemotherapy-refractory (cohort A) or previously untreated (cohort B) MSI-H/dMMR mCRC. Clinical Trial Registration: NCT04895722 (ClinicalTrials.gov).

Vibostolimab also increased T cell chemotaxis induced by activated NK cells in vitro and in vivo. Overall, blocking TIGIT/CD155 signaling enhances the antitumor effect of expanded NK cells against CRPC; this finding supports the translational application of TIGIT mAb and NK cell combination strategies from bench to bedside for CRPC treatment.

Vibostolimab was evaluated in a phase I alone or in combination with pembrolizumab...Etigilimab was tested in a phase I alone or in combination with nivolumab, but the study was stopped due to business reasons. In the phase II CITYSCAPE trial, tiragolumab demonstrated higher objective response rate and progression-free survival in combination with atezolizumab than atezolizumab alone in advanced PD-L1-high NSCLC...Anti-TIGIT antibodies are under development as a novel immunotherapy approach. A promising research area includes the combination with anti-PD-1 therapies in advanced NSCLCs.

This ongoing, open-label, multicenter, multiarm, randomized, phase 2 trial (NCT04895722) will evaluate efficacy and safety of coformulated pembro and anti–CTLA-4 quavonlimab compared with pembro monotherapy in chemotherapy-refractory stage IV dMMR/MSI-H CRC in cohort A; the study will also evaluate the efficacy and safety of 4 pembro-based combinations (coformulation of pembro with either quavonlimab, anti–LAG-3 favezelimab, or anti-TIGIT vibostolimab; anti-ILT4 MK-4830 given sequentially with pembro) compared with pembro monotherapy in previously untreated stage IV dMMR/MSI-H CRC in cohort B. Pts aged ≥18 y with histologically confirmed stage IV dMMR/MSI-H CRC who have measurable disease per RECIST v1.1 by investigator and confirmed by blinded independent central review (BICR), will be enrolled. Pts in cohort A must have experienced PD after fluoropyrimidine, irinotecan, and oxaliplatin, with or without anti-VEGF antibody, and anti-EGFR antibody for pts with left-sided tumors that are RAS WT...For both cohorts, primary end point is ORR by BICR per RECIST v1.1; secondary end points are ORR assessed by investigator, DOR and PFS assessed by BICR and by investigator per RECIST v1.1, OS, and safety and tolerability graded per NCI CTCAE v5.0. Enrollment in this trial is ongoing.

P1, N=492, Active, not recruiting, Merck Sharp & Dohme Corp. | Recruiting --> Active, not recruiting

The current phase 3 study (KeyVibe-003; ClinicalTrials.gov, NCT04738487) is comparing first-line treatment with MK-7684A, a co-formulation of vibostolimab plus pembrolizumab, versus pembrolizumab monotherapy in patients with PD-L1-positive metastatic NSCLC. This randomized, multicenter, double-blind study is enrolling adults with pathologically confirmed, previously untreated, metastatic NSCLC with PD-L1 TPS ≥1% (centrally confirmed). N/A

Combination of vibostolimab and pembrolizumab is well tolerated and has antitumor activity.

Vibostolimab plus pembrolizumab was well tolerated and demonstrated antitumor activity in patients with advanced solid tumors, including patients with advanced NSCLC.

Background: The T-cell immunoglobulin and ITIM domain (TIGIT) is highly coexpressed with programmed cell death 1 (PD-1) on both CD4 and CD8 T cells in cancers. In the part 2 dose-expansion phase, the plan is to enroll approximately 120 patients from cohorts B-E to receive up to 35 cycles of MK-7684A Q3W; 30 additional patients may be enrolled in a cohort expansion (cohort G) to receive vibostolimab monotherapy Q3W for up to 35 cycles. Cohort G will include patients with cHL or PMBCL with PD after ≥2 or ≥3 prior therapies, FL after ≥2 prior therapies, DLBCL after ≥2 prior therapies, and/or MM after ≥3 prior therapies.

The current phase 3 study (NCT04738487) is comparing first-line treatment with MK-7684A, a co-formulation of vibostolimab plus pembrolizumab, versus pembrolizumab monotherapy in patients with PD-L1–positive metastatic NSCLC. Enrollment began in April of 2021, and is ongoing at 42 sites in 11 countries. Trial Registration ClinicalTrials.gov, NCT04738487

The current phase 3 study (NCT04738487) is comparing the efficacy and safety of first-line treatment with MK-7684A, a co-formulation of vibostolimab plus pembrolizumab, versus pembrolizumab monotherapy in patients with PD-L1-positive metastatic NSCLC. Approximately 598 patients will be randomized. Enrollment began in April of 2021.

P1, N=492, Recruiting, Merck Sharp & Dohme Corp. | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

P1, N=492, Recruiting, Merck Sharp & Dohme Corp. | Trial primary completion date: Sep 2023 --> Jan 2024 | Trial completion date: Sep 2023 --> Jan 2024

P1, N=492, Recruiting, Merck Sharp & Dohme Corp. | Trial completion date: Jun 2022 --> Sep 2023 | Trial primary completion date: Jun 2022 --> Sep 2023