favezelimab (MK-4280) / Merck (MSD), Agenus - LARVOL DELTA

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

Study to Evaluate the Safety and Efficacy of a Combination of Favezelimab (MK-4280) and Pembrolizumab (MK-3475) in Participants With Hematologic Malignancies (MK-4280-003) (clinicaltrials.gov) - P1/2 | N=174 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Oct 2028 ➔ Jan 2026 | Trial primary completion date: Oct 2028 ➔ Jan 2026

Trial completion date • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Classical Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

KEYMAKER-U03 Substudy 03B: Pembrolizumab (pembro) and novel immunotherapy agents for advanced clear cell renal cell carcinoma (ccRCC). (ASCO-GU 2025) - P1/2 | "We present results from arms containing only immunotherapy regimens: arm B1 (quavonlimab [qmab; anti–CTLA-4] coformulated with pembro), arm B2 (favezelimab [fave; anti–LAG-3] coformulated with pembro), and arm B3 (pembro + MK-4830 [anti-ILT4]), and the reference (ref) arm (pembro + lenvatinib). Preliminary data from qmab/pembro (arm B1) and pembro + lenvatinib (ref arm) showed antitumor activity in pts with ccRCC that progressed on anti–PD-(L)1 and VEGF-TKI therapy. Fave/pembro (arm B2) and pembro + MK-4830 (arm B3) arms did not show clinical activity in this setting. The safety profile of each arm was manageable."

Metastases • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

Co-formulated favezelimab plus pembrolizumab versus standard-of-care in previously treated, PD-L1-positive metastatic colorectal cancer: The phase 3, randomized KEYFORM-007 study. (ASCO-GI 2025) - P3 | " Eligible pts with PD-L1 CPS ≥1, MSS/pMMR unresectable mCRC (Stage IV per AJCC 8th edition), who had progressed on or after, or could not tolerate standard treatment were randomized 1:1 to co-formulated fave 800 mg/pembro 200 mg IV Q3W (Arm A) or SOC (regorafenib 160 mg PO Q4W [QD on days 1-21] or TAS-102 35 mg/m2 PO Q4W [BID on days 1-5 and 8-12]) (Arm B). At final analysis, co-formulated fave/pembro did not improve OS vs SOC in pts with PD-L1-positive MSS/pMMR mCRC. The safety profile was manageable with no new safety signals observed."

Clinical • IO biomarker • Late-breaking abstract • Metastases • P3 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • PD-L1

Study to Evaluate the Safety and Efficacy of a Combination of Favezelimab (MK-4280) and Pembrolizumab (MK-3475) in Participants With Hematologic Malignancies (MK-4280-003) (clinicaltrials.gov) - P1/2 | N=174 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Classical Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

UPDATED ANALYSIS OF A PHASE 1/2 STUDY EVALUATING PEMBROLIZUMAB (PEMBRO) PLUS THE ANTI–LYMPHOCYTE-ACTIVATION GENE 3 (LAG-3) ANTIBODY FAVEZELIMAB FOR ANTI–PD-1–NAIVE RELAPSED OR REFRACTORY (R/R) CLASSICAL HODGKIN LYMPHOMA (CHL) (ISHL 2024) - P1/2 | "With additional follow-up, pembro+favezelimab continued to demonstrate manageable safety and sustained antitumor activity in pts with anti–PD-1–naive R/R cHL. These findings support further investigation of pembro + favezelimab"

P1/2 data • Bone Marrow Transplantation • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Hepatology • Hodgkin Lymphoma • Immunology • Lymphoma • Oncology • Pneumonia

UPDATED ANALYSIS OF A PHASE 1/2 STUDY EVALUATING PEMBROLIZUMAB (PEMBRO) PLUS THE ANTI–LYMPHOCYTE-ACTIVATION GENE 3 (LAG-3) ANTIBODY FAVEZELIMAB FOR HEAVILY PRETREATED ANTI–PD-1–REFRACTORY CLASSICAL HODGKIN LYMPHOMA (CHL) (ISHL 2024) - P1/2, P3 | "With additional follow-up, pembro plus favezelimab continued to demonstrate manageable safety and sustained antitumor activity in pts with heavily pretreated anti–PD-1–refractory R/R cHL. A coformulation of favezelimab and pembro is being evaluated (KEYFORM-008; NCT05508867)"

P1/2 data • Bone Marrow Transplantation • CNS Disorders • Diabetes • Hematological Malignancies • Hepatology • Hodgkin Lymphoma • Lymphoma • Metabolic Disorders • Oncology • Type 1 Diabetes Mellitus

Deciphering LAG-3: unveiling molecular mechanisms and clinical advancements. (PubMed, Biomark Res) - "Currently, with the approval of relatlimab, a LAG-3 blocking antibody, a third player, has been used in the fight against cancer...However, the complex biology of LAG-3 may hinder its full development as a therapeutic alternative. In this review, we provide in-depth insight into the biology of LAG-3 and its current and future development in cancer treatment."

Journal • Review • Oncology • Solid Tumor • CTLA4 • LAG3

Study to Evaluate the Safety and Efficacy of a Combination of Favezelimab (MK-4280) and Pembrolizumab (MK-3475) in Participants With Hematologic Malignancies (MK-4280-003) (clinicaltrials.gov) - P1/2 | N=174 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Apr 2028 ➔ Oct 2028 | Trial primary completion date: Apr 2028 ➔ Oct 2028

Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

KEYMAKER-U02 substudy 02C: Neoadjuvant pembrolizumab (pembro) and investigational agents followed by adjuvant pembro for stage IIIB-D melanoma (ESMO 2024) - P1/2 | "We present initial results from arm 4 (pembro + MK-4830 [anti-ILT4]) and arm 5 (favezelimab [anti-LAG-3] coformulated with pembro [fave/pembro]) and updated results from arm 1 (pembro + vibostolimab [vibo; anti-TIGIT]), arm 2 (pembro + gebasaxturev [geba; coxsackievirus A21]), and arm 3 (pembro alone). Adults with resectable stage IIIB-D melanoma were randomly assigned to open arms. All arms had manageable safety in stage IIIB-D melanoma. With the promising antitumor activity observed in this study, further investigation of pembro + vibo and fave/pembro in this setting is warranted. RFS by major pathologic response will be presented."

Clinical • Melanoma • Oncology • Solid Tumor • TIGIT

FAVEZELIMAB (ANTI-LAG-3) PLUS PEMBROLIZUMAB (PEMBRO) IN PATIENTS WITH RELAPSED OR REFRACTORY (R/R) INDOLENT NON-HODGKIN LYMPHOMA: COHORT 4 OF A MULTICOHORT OPEN-LABEL PHASE 1/2 STUDY (EHA 2024) - P1/2 | "Limited antitumor activity was noted for favezelimab plus pembro in pts with R/R iNHL in cohort 4. The safetyprofile was manageable and consistent with data from other cohorts in the study. The use of this combinationin further studies on R/R iNHL is not suggested."

Clinical • P1/2 data • Endocrine Disorders • Follicular Lymphoma • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Immunology • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pain • Pancreatitis • TINCR

PEMBROLIZUMAB PLUS THE ANTI–LAG-3 ANTIBODY FAVEZELIMAB FOR ANTI–PD-1–NAIVE RELAPSED OR REFRACTORY (R/R) CLASSICAL HODGKIN LYMPHOMA: AN UPDATED ANALYSIS OF A PHASE 1/2 STUDY (EHA 2024) - P1/2 | "In this updated analysis, pembrolizumab plus favezelimab continued to demonstrate manageable safety andsustained antitumor activity in pts with anti–PD-1–naive R/R cHL. Further investigation of pembrolizumab plusfavezelimab are warranted"

P1/2 data • Bone Marrow Transplantation • Endocrine Disorders • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Hepatology • Hodgkin Lymphoma • Immunology • Lymphoma • Melanoma • Oncology • Pneumonia • Solid Tumor

PEMBROLIZUMAB PLUS THE ANTI–LAG-3 ANTIBODY FAVEZELIMAB FOR HEAVILY PRETREATED ANTI–PD-1–REFRACTORY CLASSICAL HODGKIN LYMPHOMA (CHL): AN UPDATED ANALYSIS OF A PHASE 1/2 STUDY (EHA 2024) - P1/2, P3 | "In this updated analysis, pembrolizumab plus favezelimab continued to demonstrate manageable safety andantitumor activity in pts with heavily pretreated anti–PD-1–refractory cHL. A coformulation of favezelimab andpembrolizumab is being evaluated in anti–PD-1–refractory cHL in the phase 3 KEYFORM-008 study(NCT05508867)."

P1/2 data • Bone Marrow Transplantation • CNS Disorders • Diabetes • Endocrine Disorders • Fatigue • Hematological Malignancies • Hepatology • Hodgkin Lymphoma • Lymphoma • Metabolic Disorders • Oncology • Type 1 Diabetes Mellitus

A phase 1/2 study of favezelimab in combination with pembrolizumab for heavily pretreated anti–PD-1–refractory classical Hodgkin lymphoma (cHL): An updated analysis. (ASCO 2024) - P1/2, P3 | "After additional follow-up, favezelimab + pembrolizumab continued to demonstrate manageable safety and antitumor activity in pts with heavily pretreated anti–PD-1–refractory cHL. The phase 3 KEYFORM-008 study (NCT05508867) will evaluate a coformulation of favezelimab and pembrolizumab in pts with anti–PD-1–refractory cHL."

Combination therapy • P1/2 data • Bone Marrow Transplantation • CNS Disorders • Diabetes • Endocrine Disorders • Fatigue • Hematological Disorders • Hematological Malignancies • Hepatology • Hodgkin Lymphoma • Lymphoma • Metabolic Disorders • Oncology • Transplantation • Type 1 Diabetes Mellitus

A phase 1/2 study of favezelimab in combination with pembrolizumab for anti–PD-1–naive relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL): An updated analysis. (ASCO 2024) - P1/2 | "With additional follow-up, favezelimab plus pembrolizumab continued to demonstrate sustained antitumor activity and manageable safety in pts with anti–PD-1–naive R/R cHL. Further studies to investigate this combination are warranted."

Combination therapy • P1/2 data • Bone Marrow Transplantation • Endocrine Disorders • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Hepatology • Hodgkin Lymphoma • Immunology • Lymphoma • Oncology • Pneumonia • Transplantation

Study to Evaluate the Safety and Efficacy of a Combination of Favezelimab (MK-4280) and Pembrolizumab (MK-3475) in Participants With Hematologic Malignancies (MK-4280-003) (clinicaltrials.gov) - P1/2 | N=174 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Oct 2027 ➔ Apr 2028 | Trial primary completion date: Oct 2027 ➔ Apr 2028

Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Phase 2 KEYNOTE-057 cohort C: Coformulations of pembrolizumab (pembro) and favezelimab or vibostolimab for patients with bacillus Calmette-Guérin (BCG)–unresponsive high-risk (HR) non–muscle-invasive bladder cancer (NMIBC) (EAU 2024) - No abstract available

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

Study of Favezelimab (MK-4280) as Monotherapy and in Combination With Pembrolizumab (MK-3475) With or Without Chemotherapy or Lenvatinib (MK-7902) AND Favezelimab/Pembrolizumab (MK-4280A) as Monotherapy in Adults With Advanced Solid Tumors (MK-4280-001) (clinicaltrials.gov) - P1 | N=482 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Monotherapy • Trial completion • Oncology • Solid Tumor

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 in Combination with Pembrolizumab in Patients with Anti–PD-1–Naive Relapsed or Refractory Classical Hodgkin Lymphoma: Updated Analysis of an Open-Label Phase 1/2 Study (ASH 2023) - P1/2 | "With additional follow-up, the combination of favezelimab and pembrolizumab continued to demonstrate sustained antitumor activity and manageable safety in patients with anti–PD-1–naive R/R cHL. Analyses are underway to identify biomarkers predictive of response to the combination of favezelimab and pembrolizumab. Further studies to investigate this combination are warranted."

Clinical • Combination therapy • IO biomarker • P1/2 data • Bone Marrow Transplantation • Endocrine Disorders • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Hepatology • Hodgkin Lymphoma • Immunology • Lymphoma • Melanoma • Oncology • Pneumonia • Solid Tumor • Transplantation • LAG3

Favezelimab in Combination with Pembrolizumab in Patients with Heavily Pretreated Anti–PD-1–Refractory Classical Hodgkin Lymphoma: Updated Analysis of an Open-Label Phase 1/2 Study (ASH 2023) - P1/2, P3 | "After additional follow-up, the combination of favezelimab + pembrolizumab continued to demonstrate manageable safety and antitumor activity in patients with heavily pretreated anti–PD-1–refractory cHL. Analyses are underway to identify biomarkers predictive of response to the combination of favezelimab and pembrolizumab. The phase 3 KEYFORM-008 study (NCT05508867) is being conducted to evaluate a coformulation of favezelimab and pembrolizumab in patients with anti–PD-1–refractory cHL."

Clinical • Combination therapy • IO biomarker • P1/2 data • Acute Graft versus Host Disease • Bone Marrow Transplantation • CNS Disorders • Diabetes • Endocrine Disorders • Fatigue • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Hepatology • Hodgkin Lymphoma • Immunology • Lymphoma • Melanoma • Metabolic Disorders • Oncology • Solid Tumor • Transplantation • Type 1 Diabetes Mellitus

Favezelimab (anti–LAG-3) Plus Pembrolizumab in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL): Cohort 3 of a Multicohort Open-Label Phase 1/2 Study (ASH 2023) - P1/2 | "Favezelimab 800 mg plus pembrolizumab 200 mg had limited antitumor activity in patients with DLBCL in cohort 3. Analyses are underway to identify biomarkers predictive of response to the combination of favezelimab and pembrolizumab. The safety profile was manageable and consistent with that observed in other cohorts in the study."

Clinical • IO biomarker • P1/2 data • Bone Marrow Transplantation • Constipation • Cough • Diffuse Large B Cell Lymphoma • Endocrine Disorders • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pain • Pruritus • Respiratory Diseases • Richter's Syndrome • Transplantation

External reproducibility of PD-L1 IHC 22C3 pharmDx for colorectal carcinoma specimens at CPS ≥ 1 cutoff (SITC 2023) - P1 | "1 Recent results from MK4280–001 phase I clinical study (NCT02720068) have demonstrated clinical activity of a combined therapy regimen of the anti-LAG3 antibody favezelimab plus pembrolizumab in patients with microsatellite stable metastatic CRC whose tumors express PD-L1 with a Combined Positive Score (CPS) ≥ 1. 4% OA for both endpoints. Conclusions This study demonstrates high external lab reproducibility of PD-L1 IHC 22C3 pharmDx with respect to PD-L1 expression in CRC at the CPS ≥ 1 cutoff."

IO biomarker • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • PD-L1

Study to Evaluate the Safety and Efficacy of a Combination of Favezelimab (MK-4280) and Pembrolizumab (MK-3475) in Participants With Hematologic Malignancies (MK-4280-003) (clinicaltrials.gov) - P1/2 | N=174 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Feb 2028 ➔ Oct 2027 | Trial primary completion date: Feb 2028 ➔ Oct 2027

Trial completion date • Trial primary completion date • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Study to Evaluate the Safety and Efficacy of a Combination of Favezelimab (MK-4280) and Pembrolizumab (MK-3475) in Participants With Hematologic Malignancies (MK-4280-003) (clinicaltrials.gov) - P1/2 | N=174 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Oct 2027 ➔ Feb 2028 | Trial primary completion date: Oct 2027 ➔ Feb 2028

Trial completion date • Trial primary completion date • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology