quavonlimab (MK-1308)

P1/2, N=100, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed | N=200 --> 100 | Trial completion date: Apr 2030 --> Aug 2025 | Trial primary completion date: Apr 2030 --> Aug 2025

P2, N=245, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed | Trial completion date: Nov 2025 --> Jun 2025 | Trial primary completion date: Nov 2025 --> Jun 2025

P2, N=318, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Jun 2025 --> Nov 2025 | Trial primary completion date: Jun 2025 --> Nov 2025

P1/2, N=413, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

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

Results from this study may support triplet combination therapies as a potential new standard of care for advanced ccRCC. Clinical trial registry: NCT04736706 (ClinicalTrials.gov).

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).

Patients were categorized by T-cell-inflamed gene expression profile (TcellGEP) and tumor mutational burden (TMB) status and randomly assigned 1:1:1 to receive pembrolizumab + lenvatinib, pembrolizumab + quavonlimab or pembrolizumab + favezelimab. These data demonstrate the feasibility of prospective TcellGEP and TMB assessment to study the clinical activity of first-line pembrolizumab-based combination therapies in advanced NSCLC. ClinicalTrials.gov registration: NCT03516981 .

P1/2, N=348, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Oct 2023 --> Apr 2024 | Trial primary completion date: Oct 2023 --> Apr 2024

P1/2, N=348, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Jan 2024 --> Aug 2023 | Trial primary completion date: Jan 2024 --> Aug 2023

P2, N=318, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Oct 2025 --> Jun 2025 | Trial primary completion date: Oct 2025 --> Jun 2025

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.