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

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 | Terminated | Sponsor: Merck Sharp & Dohme LLC | Completed ➔ Terminated; MK-7684A-007 was terminated early due to futility. A non-submission CSR, not intended to support any registration, was issued; therefore, an abbreviated CSR was generated.

Trial termination • 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

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

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 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

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 | Terminated | Sponsor: Merck Sharp & Dohme LLC | Completed ➔ Terminated; Business Reasons

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

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

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

Study of Pembrolizumab (MK-3475) and Pembrolizumab With Other Investigational Agents in Participants With High Risk Non-muscle Invasive Bladder Cancer (MK-3475-057/KEYNOTE-057) (clinicaltrials.gov) - P2 | N=296 | Terminated | Sponsor: Merck Sharp & Dohme LLC | Completed ➔ Terminated; Business Reasons

Trial termination • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • PD-L1

KEYVIBE-006: Study of Pembrolizumab/Vibostolimab (MK-7684A) in Combination With Concurrent Chemoradiotherapy Followed by Pembrolizumab/Vibostolimab Versus Concurrent Chemoradiotherapy Followed by Durvalumab in Participants With Stage III Non-small Cell Lung Cancer (MK-7684A-006) (clinicaltrials.gov) - P3 | N=610 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

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

Biomarker analysis of coformulation of vibostolimab with pembrolizumab (vibo/pembro) with or without docetaxel for metastatic non–small-cell lung cancer (mNSCLC) after chemotherapy and immunotherapy (SITC 2025) - P2 | "Additional biomarker data will be presented.Conclusions These biomarker analyses showed that higher TIGIT IHC was associated with numerically longer PFS and OS in participants with mNSCLC previously treated with an anti-PD-(L)1 and platinum-based chemotherapy receiving vibo/pembro with docetaxel; this benefit was not observed with vibo/pembro alone.Trial Registration ClinicalTrials.gov identifier, NCT04725188Ethics Approval The study was conducted in accordance with principles of Good Clinical Practice and approved by the appropriate institutional review boards and regulatory agencies. All participants provided written informed consent before enrolling.Abstract 508 Table 1View inline•Open as popupPFS and OS HRa estimates for biomarker subgroups"

Biomarker • IO biomarker • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1 • TIGIT

A Study of Adjuvant Pembrolizumab/Vibostolimab (MK-7684A) Versus Pembrolizumab for Resected High-Risk Melanoma in Participants With High-Risk Stage II-IV Melanoma (MK-7684A-010/KEYVIBE-010) (clinicaltrials.gov) - P3 | N=1594 | Terminated | Sponsor: Merck Sharp & Dohme LLC | Completed ➔ Terminated; Business Reason

Trial termination • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor

MK-7684A (Vibostolimab [Vibo] Plus Pembrolizumab [Pembro] Coformulation) With/Without Docetaxel in Metastatic NSCLC After Platinum-Chemotherapy (Chemo) and Immunotherapy (ESMO-IO 2023) - P2 | "Conclusions In pts with mNSCLC previously treated with anti-PD-(L)1 therapy and platinum-doublet chemo, MK-7684A and MK-7684A + docetaxel vs docetaxel alone did not show statistically significant differences in PFS, and no new safety signals. Follow-up is ongoing."

Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1 • TIGIT

Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365) (clinicaltrials.gov) - P1/2 | N=1200 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • 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 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Completed ➔ Active, not recruiting | N=49 ➔ 390

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

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