favezelimab/pembrolizumab (MK-4280A) / Merck (MSD) - LARVOL DELTA

KEYMAKER-U03B: Substudy 03B: A Study of Immune and Targeted Combination Therapies in Participants With Second Line Plus (2L+) Renal Cell Carcinoma (MK-3475-03B/KEYMAKER-U03) (clinicaltrials.gov) - P1/2 | N=263 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • PD-L1

Substudy 03A: A Study of Immune and Targeted Combination Therapies in Participants With First Line (1L) Renal Cell Carcinoma (MK-3475-03A) (clinicaltrials.gov) - P1/2 | N=393 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results. (PubMed, Nat Med) - P2 | "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 ."

Biomarker • Combination therapy • IO biomarker • Journal • P2 data • Tumor mutational burden • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TMB

KEYNOTE-495/KeyImPaCT: updated analysis of a biomarker-directed, randomized, phase 2 trial of pembrolizumab-based combination therapy for non-small cell lung cancer (SITC 2022) - P2 | "Methods Patients with previously untreated stage IV NSCLC were categorized by Tcell inf GEP and TMB dual biomarker status (Tcell inf GEP low TMB non-high , Tcell inf GEP low TMB high , Tcell inf GEP non-low TMB non-high , Tcell inf GEP non-low TMB high ) then randomly assigned 1:1:1 to receive pembrolizumab (200 mg IV Q3W) plus the multikinase inhibitor (targeting VEGFRs 1-3, FGFRs 1-4, PDGFRα, RET, and KIT) lenvatinib (20 mg oral QD), CTLA-4 inhibitor quavonlimab (75 mg IV Q6W), or LAG-3 inhibitor favezelimab (initially 200 mg and then 800 mg IV Q3W). Although response in the pembrolizumab+favezelimab arm did not reach the efficacy bar, there was a trend toward improved ORR in the Tcell inf GEP non-low TMB high subgroup versus the other 3 biomarker-defined subgroups; median PFS and OS were also numerically longer in the Tcell inf GEP non-low TMB high subgroup compared with the other 3 biomarker-defined subgroups. Prospective assessment of dual biomarkers, as..."

Biomarker • Clinical • Combination therapy • IO biomarker • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • LAG3 • PDGFRA • TMB

Favezelimab (anti–LAG-3) plus pembrolizumab in patients with anti–PD-1–naive relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL): An open-label phase 1/2 study. (ASCO 2022) - P1/2 | "Favezelimab 800 mg + pembrolizumab 200 mg Q3W demonstrated a tolerable safety profile and effective antitumor activity in pts with anti–PD-1–naïve R/R cHL. Further studies will be useful to compare its activity to that of pembrolizumab alone."

Clinical • P1/2 data • Bone Marrow Transplantation • Endocrine Disorders • Fatigue • Hematological Disorders • Hematological Malignancies • Hepatology • Hodgkin Lymphoma • Immunology • Inflammation • Lymphoma • Musculoskeletal Pain • Oncology • Pain • Transplantation • LAG3

COFORMULATED FAVEZELIMAB/PEMBROLIZUMAB VERSUS CHEMOTHERAPY IN PARTICIPANTS WITH RELAPSED OR REFRACTORY CLASSIC HODGKIN LYMPHOMA: RESULTS OF THE RANDOMIZED PHASE 2 KEYFORM-008 STUDY (EHA 2026) - P2 | "Pts must have had PD per investigator ≤12 wk from last dose of anti–PD-(L)1–based therapy (received for ≥3 mo with ≥2 doses) and must have exhausted available tx options with known clinical benefit, including being ineligible for or having not responded to or progressed after autologous stem cell transplant and brentuximab vedotin. Pts were randomly assigned 1:1 to favezelimab 800 mg/pembrolizumab 200 mg IV Q3W or chemotherapy (gemcitabine 800- 1200 mg/m 2 IV on days 1 and 8 of a 21-day cycle or bendamustine 90-120 mg/m 2 IV on days 1 and 2 of either a 21- or 28-day cycle)...Although ORR was notably lower for favezelimab/pembrolizumab, disease control (CR+PR+SD) was similar between the two groups. KEYFORM-008 was discontinued based on the sponsor's business decision to end the entire favezelimab clinical development program and was not driven by safety or efficacy concerns."

Clinical • P2 data • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Infectious Disease • Lymphoma • Septic Shock • LAG3

Updated Results from an Open-Label Phase 1/2 Study of Favezelimab (anti–LAG-3) Plus Pembrolizumab in Relapsed or Refractory Classical Hodgkin Lymphoma after Anti–PD-1 Treatment (ASH 2022) - P1/2 | "After additional follow-up, favezelimab plus pembrolizumab combination therapy continued to demonstrate sustained antitumor activity and acceptable safety in pts with R/R cHL whose disease progressed following anti–PD-1 therapy. A phase 3 study is planned to further investigate the promising results found in this patient population."

Clinical • P1/2 data • Acute Graft versus Host Disease • Bone Marrow Transplantation • Cardiovascular • CNS Disorders • Endocrine Disorders • Fatigue • Graft versus Host Disease • Heart Failure • Hematological Disorders • Hematological Malignancies • Hepatology • Hodgkin Lymphoma • Immunology • Inflammation • Lymphoma • Melanoma • Metabolic Disorders • Migraine • Musculoskeletal Pain • Neutropenia • Oncology • Pain • Solid Tumor • Transplantation • LAG3

Safety and Dose-Expansion Study of Combination Favezelimab (anti–LAG-3) Plus Pembrolizumab in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma Refractory to Anti–PD-1 Treatment (ISHL 2022) - P1/2 | "Favezelimab 800 mg + pembrolizumab 200 mg Q3W demonstrated acceptable safety and effective antitumor activity in pts with R/R cHL and PD following anti–PD-1 therapy. This combination shows potential to reinduce a response in this pt population."

Clinical • Bone Marrow Transplantation • Endocrine Disorders • Fatigue • Hematological Disorders • Hematological Malignancies • Hepatology • Hodgkin Lymphoma • Immunology • Inflammation • Lymphoma • Oncology • Transplantation • LAG3

FAVEZELIMAB PLUS PEMBROLIZUMAB IN ANTI–PD-1–REFRACTORY CLASSICAL HODGKIN LYMPHOMA (CHL): ESTIMATING THE RELATIVE EFFICACY OF FAVEZELIMAB (ICML 2023) - "In this analysis, favezelimab + pembrolizumab was associated with a higher ORR and deeper responses than pembrolizumab alone in pts with anti–PD-1–refractory R/R cHL, indicating that favezelimab contributed substantially to the efficacy observed in MK-4280-003."

Clinical • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • LAG3

Pembrolizumab with favezelimab or vibostolimab for patients with bacillus Calmette-Guérin (BCG)–unresponsive high-risk (HR) non–muscle-invasive bladder cancer (NMIBC): Phase 2 KEYNOTE-057 cohort C. (ASCO-GU 2024) - P2 | "Enrollment is ongoing in Asia, Australia, Europe, North America, and South America. Clinical trial information: NCT02625961."

Clinical • P2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • LAG3 • TIGIT

Favezelimab plus pembrolizumab for anti-PD-1-refractory classic Hodgkin lymphoma: an open-label phase 1/2 study. (PubMed, Blood Neoplasia) - P1/2 | "Favezelimab plus pembrolizumab showed manageable safety and antitumor activity in heavily pretreated anti-PD-1-refractory cHL. This trial was registered at www.clinicaltrials.gov as NCT03598608."

Journal • P1/2 data • Autoimmune Hepatitis • B Cell Lymphoma • Classical Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

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

Population Pharmacokinetic, Exposure-Response Efficacy and Safety Analyses of Favezelimab in Patients With Solid Tumors. (PubMed, Clin Transl Sci) - "Favezelimab population pharmacokinetics (popPK) was evaluated using data from 2 trials; a Phase 1 study evaluating favezelimab across a range of doses (7 to 800 mg administered intravenously [IV] every 3 weeks [Q3W]) in patients with advanced solid tumors, and a Phase 3 study evaluating 800 mg IV Q3W favezelimab combined with pembrolizumab (200 mg Q3W) in patients with programmed death ligand 1 (PD-L1) positive colorectal cancer (CRC). No covariates were associated with ORR. This analysis was used to characterize variability in favezelimab pharmacokinetics and support the choice of Phase 3 dose."

Clinical • Journal • PK/PD data • Colorectal Cancer • Gastric Cancer • Oncology • Solid Tumor • LAG3 • PD-L1

KEYMAKER-U02 Substudy 02B: Substudy 02B: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With First Line (1L) Advanced Melanoma (MK-3475-02B/KEYMAKER-U02) (clinicaltrials.gov) - P1/2 | N=335 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Melanoma • Oncology • Solid Tumor

Safety and Efficacy Study of Investigational Agents as Monotherapy or in Combination With Pembrolizumab (MK-3475) for the Treatment of Extensive-Stage Small Cell Lung Cancer (ES-SCLC) in Need of Second-Line Therapy (MK-3475-B98/KEYNOTE-B98) (clinicaltrials.gov) - P1/2 | N=110 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Lung Cancer • Oncology • Small Cell Lung 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

Results from KEYNOTE-B98: A phase 1b/2 study of pembrolizumab plus investigational agents in patients with anti-PD-(L)1-refractory extensive-stage small-cell lung cancer (ES-SCLC) (AACR 2024) - P1/2 | "In the KEYNOTE-B98 study of anti-PD-(L)1-refractory ES-SCLC, no new safety signals were identified for the pembro-based combinations investigated. Modest antitumor activity was observed with MK-1308A ± lenvatinib, but no activity for MK-1308A + MK-4830 or for MK-4280A. This study provided proof-of-concept for the feasibility of platform trials in 2L ES-SCLC."

Clinical • P1/2 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Safety and Efficacy Study of Investigational Agents as Monotherapy or in Combination With Pembrolizumab (MK-3475) for the Treatment of Extensive-Stage Small Cell Lung Cancer (ES-SCLC) in Need of Second-Line Therapy (MK-3475-B98/KEYNOTE-B98) (clinicaltrials.gov) - P1/2 | N=110 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial primary completion date: May 2026 ➔ Dec 2029

Monotherapy • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

KeyForm-010: Study of Favezelimab Coformulated With Pembrolizumab (MK-4280A) in Participants With Selected Solid Tumors (MK-4280A-010) (clinicaltrials.gov) - P2 | N=160 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Pan tumor • pMMR • Trial completion • Endometrial Cancer • Oncology • 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

KeyImPaCT: A Study of Biomarker-Directed, Pembrolizumab (MK-3475) Based Combination Therapy for Advanced Non-Small Cell Lung Cancer (MK-3475-495/KEYNOTE-495) (clinicaltrials.gov) - P2 | N=192 | Not yet recruiting | Sponsor: Merck Sharp & Dohme Corp. | Initiation date: Jul 2018 ➔ Dec 2018

Biomarker • Trial initiation date • Tumor mutational burden • Non Small Cell Lung Cancer • ALK • EGFR • ROS1

KeyImPaCT: A Study of Biomarker-Directed, Pembrolizumab (MK-3475) Based Combination Therapy for Advanced Non-Small Cell Lung Cancer (MK-3475-495/KEYNOTE-495) (clinicaltrials.gov) - P2 | N=318 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Jun 2025 ➔ Nov 2025 | Trial primary completion date: Jun 2025 ➔ Nov 2025

Biomarker • Trial completion date • Trial primary completion date • Tumor mutational burden • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1

KeyImPaCT: A Study of Biomarker-Directed, Pembrolizumab (MK-3475) Based Combination Therapy for Advanced Non-Small Cell Lung Cancer (MK-3475-495/KEYNOTE-495) (clinicaltrials.gov) - P2 | N=318 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | Trial completion date: May 2022 ➔ Jan 2023 | Trial primary completion date: May 2022 ➔ Jan 2023

Biomarker • Trial completion date • Trial primary completion date • Tumor mutational burden • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer • ALK • EGFR • ROS1

KeyImPaCT: A Study of Biomarker-Directed, Pembrolizumab (MK-3475) Based Combination Therapy for Advanced Non-Small Cell Lung Cancer (MK-3475-495/KEYNOTE-495) (clinicaltrials.gov) - P2 | N=245 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed | Trial completion date: Nov 2025 ➔ Jun 2025 | Trial primary completion date: Nov 2025 ➔ Jun 2025

Biomarker • Trial completion • Trial completion date • Trial primary completion date • Tumor mutational burden • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1

KeyImPaCT: A Study of Biomarker-Directed, Pembrolizumab (MK-3475) Based Combination Therapy for Advanced Non-Small Cell Lung Cancer (MK-3475-495/KEYNOTE-495) (clinicaltrials.gov) - P1/2 | N=288 | Not yet recruiting | Sponsor: Merck Sharp & Dohme Corp.

Biomarker • New P1/2 trial • New P2 trial • Tumor mutational burden • Non Small Cell Lung Cancer • ALK • EGFR • ROS1