vibostolimab/pembrolizumab (MK-7684A) / Merck (MSD) - LARVOL DELTA

Vibostolimab coformulated with pembrolizumab versus pembrolizumab alone as adjuvant therapy for high-risk stage IIB-IV melanoma (KEYVIBE-010): a randomised, double-blind, phase 3 study. (PubMed, Lancet Oncol) - P3 | "Vibostolimab coformulated with pembrolizumab did not provide additional clinical benefit versus pembrolizumab as adjuvant therapy in participants with resected stage IIB-IV melanoma. Pembrolizumab monotherapy remains a standard of care for resected high-risk melanoma."

Journal • P3 data • Cardiovascular • CNS Disorders • Cutaneous Melanoma • Dermatology • Endocrine Disorders • Immunology • Melanoma • Myasthenia Gravis • Myositis • Nephrology • Oncology • Pruritus • Renal Disease • Solid Tumor

KEYMAKER-U04 Substudy: A Study of Efficacy and Safety of Pembrolizumab Plus Enfortumab Vedotin (EV) +/- Investigational Agents in First-Line Metastatic Urothelial Carcinoma (mUC) (MK-3475-04B/KEYMAKER-U04) (clinicaltrials.gov) - P1/2 | N=49 | Completed | Sponsor: Merck Sharp & Dohme LLC | N=37 ➔ 49

Enrollment change • Oncology • Solid Tumor • Urothelial Cancer • PD-L1

Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365) (clinicaltrials.gov) - P1 | N=210 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | Trial primary completion date: Apr 2020 ➔ Apr 2018

Trial primary completion date • Castration-Resistant Prostate Cancer • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365) (clinicaltrials.gov) - P1 | N=180 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | Trial primary completion date: Apr 2018 ➔ Mar 2020

Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365) (clinicaltrials.gov) - P1 | N=400 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | Active, not recruiting ➔ Recruiting | Trial completion date: Apr 2020 ➔ May 2022

Enrollment open • Trial completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365) (clinicaltrials.gov) - P1 | N=1000 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | Trial completion date: Dec 2023 ➔ May 2025 | Trial primary completion date: Jun 2021 ➔ May 2025

Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365) (clinicaltrials.gov) - P1 | N=210 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | Not yet recruiting ➔ Recruiting

Enrollment open • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365) (clinicaltrials.gov) - P1/2 | N=1000 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | Phase classification: P1 ➔ P1/2

Phase classification • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365) (clinicaltrials.gov) - P1 | N=180 | Active, not recruiting | Sponsor: Merck Sharp & Dohme Corp. | Recruiting ➔ Active, not recruiting

Enrollment closed • Castration-Resistant Prostate Cancer • Prostate Adenocarcinoma • Prostate Cancer

Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365) (clinicaltrials.gov) - P1 | N=1000 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | N=400 ➔ 1000

Enrollment change • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365) (clinicaltrials.gov) - P1/2 | N=1200 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: May 2025 ➔ Oct 2027 | Trial primary completion date: May 2025 ➔ Oct 2027

Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer

Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365) (clinicaltrials.gov) - P1 | N=400 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | Trial primary completion date: Mar 2020 ➔ Jun 2021

Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365) (clinicaltrials.gov) - P1 | N=210 | Not yet recruiting | Sponsor: Merck Sharp & Dohme Corp.

New P1 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365) (clinicaltrials.gov) - P1 | N=400 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | Trial completion date: May 2022 ➔ Dec 2023

Trial completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365) (clinicaltrials.gov) - P1 | N=400 | Active, not recruiting | Sponsor: Merck Sharp & Dohme Corp. | N=180 ➔ 400

Enrollment change • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

KEYMAKER-U04 Substudy: A Study of Efficacy and Safety of Pembrolizumab Plus Enfortumab Vedotin (EV) +/- Investigational Agents in First-Line Metastatic Urothelial Carcinoma (mUC) (MK-3475-04B/KEYMAKER-U04) (clinicaltrials.gov) - P1/2 | N=390 | Completed | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Completed

Trial completion • Oncology • Solid Tumor • Urothelial Cancer • PD-L1

Coformulation of Pembrolizumab/Vibostolimab (MK-7684A) Versus Pembrolizumab (MK-3475) Monotherapy for Programmed Cell Death 1 Ligand 1 (PD-L1) Positive Metastatic Non-Small Cell Lung Cancer (MK-7684A-003, KEYVIBE-003) (clinicaltrials.gov) - P3 | N=1264 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Monotherapy • Trial completion • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-1 • PD-L1 • ROS1

Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365) (clinicaltrials.gov) - P1/2 | N=1200 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Oct 2027 ➔ Jul 2028

Trial completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Vibostolimab coformulated with pembrolizumab versus pembrolizumab alone as adjuvant therapy for high-risk stage IIB–IV melanoma (KEYVIBE-010): a randomised, double-blind, phase 3 study (Lancet Oncol) - "At the time of the first interim analysis, a total of 119 (8%) of 1402 participants had had a recurrence-free survival event, including 67 (10%) of 701 in the vibostolimab–pembrolizumab group and 52 (7%) of 701 in the pembrolizumab alone group. The median recurrence-free survival was not reached in either group; the hazard ratio for recurrence-free survival in the vibostolimab–pembrolizumab group versus pembrolizumab alone group was 1·25 (95% CI 0·9–1·8)."

P3 data • Melanoma

Coformulated vibostolimab/pembrolizumab plus chemotherapy as first-line therapy vs atezolizumab plus chemotherapy for extensive-stage small-cell lung cancer (ES-SCLC): randomized, phase 3 KEYVIBE-008 (SITC 2024) - P3 | "Background Etoposide with platinum-chemotherapy (EP) plus immunotherapy (e.g. atezolizumab) is the recommended treatment for ES-SCLC.1 First-line pembrolizumab plus EP significantly improved PFS but not OS vs placebo plus EP in ES-SCLC in the KEYNOTE-604 study.2 Vibostolimab, an anti–T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) antibody, showed antitumor activity with pembrolizumab in NSCLC.3 The KEYVIBE-008 study evaluated vibostolimab coformulated with pembrolizumab (vibostolimab/pembrolizumab) plus EP as first-line therapy for ES-SCLC (NCT05224141). Methods Patients (≥18 years) with histologically/cytologically confirmed untreated ES-SCLC were randomized 1:1 to vibostolimab/pembrolizumab (200 mg each) Q3W or atezolizumab 1200 mg Q3W; patients also received EP (cisplatin or carboplatin) for the first 4 cycles...All patients provided written informed consent before enrollment. An external independent data and safety monitoring committee..."

Clinical • Late-breaking abstract • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • TIGIT

KEYVIBE 007: Study of Pembrolizumab/Vibostolimab Coformulation (MK-7684A) in Combination With Chemotherapy Versus Pembrolizumab Plus Chemotherapy in Participants With Metastatic Non-Small Cell Lung Cancer (MK-7684A-007/KEYVIBE-007) (clinicaltrials.gov) - P3 | N=739 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

A multicohort, open-label, phase 2 basket study of the coformulation of vibostolimab with pembrolizumab, with or without other anticancer therapies, in select solid tumors (AACR 2022) - P2 | "Enrollment is ongoing. >"

Clinical • IO biomarker • P2 data • Pan tumor • Oncology • Solid Tumor • CD4 • CD8 • TIGIT

A randomized, double-blind, phase 3 trial of MK-7684A plus chemotherapy versus pembrolizumab plus chemotherapy as first-line therapy for metastatic non–small cell lung cancer (NSCLC): KeyVibe-007. (ASCO 2022) - P3 | "Patients are randomized 1:1 to receive MK-7684A (MK-7684 200 mg + pembro 200 mg) IV or pembro 200 mg IV plus chemotherapy (squamous: carboplatin area under the curve [AUC] 6 mg/mL/min plus paclitaxel 200 mg/m2 or nab-paclitaxel 100 mg/m2 [days 1, 8, 15]; nonsquamous: pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 or carboplatin AUC 5 mg/mL/min) Q3W for 4 cycles followed by MK-7684A or pembro Q3W, per randomized therapy, for up to 31 additional cycles (plus continued pemetrexed maintenance, nonsquamous only) or until PD, unacceptable AEs, investigator decision, or patient withdrawal. AEs are graded according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Enrollment is ongoing."

Clinical • IO biomarker • P3 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • NECTIN2 • PD-L1 • PVR • ROS1 • TIGIT

Coformulated vibostolimab/pembrolizumab in advanced cervical cancer: KEYVIBE-005 (ESMO-GC 2024) - P2 | "Efficacy outcomes with coformulated vibo/pembro were not superior to pembro in pts with previously treated PD-L1+ cervical cancer, consistent with that observed in other anti-TIGIT trials. No new safety signals were identified."

Metastases • Cervical Cancer • Oncology • Septic Shock • Solid Tumor • PD-L1 • TIGIT

Vibostolimab coformulated with pembrolizumab versus pembrolizumab alone as adjuvant therapy for high-risk stage IIB to IV melanoma in the phase 3 KEYVIBE-010 trial: results from participants enrolled in China (ESMO Asia 2025) - P3 | "In Chinese pts with resected stage IIB-IV melanoma, adjuvant vibo/pembro did not provide additional clinical benefit vs pembro alone, consistent with the global population. Pembro monotherapy remains a standard of care in this setting."

Clinical • P3 data • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • TIGIT