MK-4830

P2, N=160, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

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

P1/2, N=110, Recruiting, Merck Sharp & Dohme LLC | Active, not recruiting --> Recruiting | N=80 --> 110 | Trial completion date: Nov 2026 --> Nov 2029 | Trial primary completion date: Nov 2026 --> May 2026

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

P2, N=320, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

P1/2, N=120, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

P1, N=13, Completed, Presage Biosciences

P1/2, N=80, Active, not recruiting, Merck Sharp & Dohme LLC | Phase classification: P1b/2 --> P1/2

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, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Dec 2026 --> Sep 2028 | Trial primary completion date: Feb 2025 --> Nov 2026

P2, N=120, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Feb 2032 --> Sep 2025 | Trial primary completion date: Feb 2032 --> Sep 2025

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

P2, N=160, Active, not recruiting, Merck Sharp & Dohme LLC | Trial primary completion date: Oct 2024 --> Dec 2023

P1/2, N=370, Active, not recruiting, Merck Sharp & Dohme LLC | Phase classification: P1b/2 --> P1/2

P1/2, N=200, Recruiting, Merck Sharp & Dohme LLC | N=300 --> 200

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

P2, N=120, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

P1b/2, N=370, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

P2, N=160, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting | Trial completion date: Jun 2025 --> Dec 2024

P1, N=442, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

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).

(2022 Clin Cancer Res 28: 57-70) reported encouraging results of the initial clinical study combining the ILT4 antagonist mAb MK-4830 with pembrolizumab. Doses of CDX-585 up to 60 mg/kg were well tolerated in cynomolgus macaques and displayed a favorable pharmacokinetic profile. Together these data demonstrate that CDX-585 effectively combines PD-1 and ILT4 blockade into one molecule with favorable biophysical and functional characteristics supporting the initiation of a dose-escalation clinical trial in patients with advanced solid tumors.

P1, N=15, Recruiting, Presage Biosciences | N=24 --> 15

P2, N=320, Recruiting, Merck Sharp & Dohme LLC | Trial primary completion date: Sep 2024 --> Sep 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.

P2, N=120, Recruiting, Merck Sharp & Dohme Corp. | N=60 --> 120

P1, N=24, Recruiting, Presage Biosciences | N=36 --> 24

P2, N=320, Recruiting, Merck Sharp & Dohme Corp. | N=240 --> 320 | Trial completion date: Sep 2024 --> Aug 2025

This first-in-class MK-4830 antibody dosed as monotherapy and in combination with pembrolizumab was well tolerated with no unexpected toxicities, and demonstrated dose-related evidence of target engagement and antitumor activity. Inflammation intrinsic to the ILT4 mechanism may be facilitated by alleviating the myeloid suppressive components of the tumor microenvironment, supporting the target of ILT4 as a potential novel immunotherapy in combination with an anti-PD-1/PD-L1 agent.

P1, N=410, Recruiting, Merck Sharp & Dohme Corp. | N=290 --> 410

P1, N=36, Recruiting, Presage Biosciences | Not yet recruiting --> Recruiting | N=12 --> 36 | Initiation date: Feb 2021 --> Jun 2021

P1, N=290, Recruiting, Merck Sharp & Dohme Corp. | Trial completion date: Jul 2023 --> Nov 2024 | Trial primary completion date: Jul 2023 --> Nov 2024

P1, N=12, Not yet recruiting, Presage Biosciences | Trial completion date: Dec 2030 --> Dec 2031 | Initiation date: Nov 2020 --> Feb 2021 | Trial primary completion date: Dec 2030 --> Dec 2031

P2, N=60, Recruiting, Merck Sharp & Dohme Corp. | Suspended --> Recruiting

P1, N=12, Not yet recruiting, Presage Biosciences

P2, N=60, Suspended, Merck Sharp & Dohme Corp. | Initiation date: May 2020 --> Nov 2020

P2, N=60, Suspended, Merck Sharp & Dohme Corp. | Not yet recruiting --> Suspended