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

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, P2 | "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 • Classical Hodgkin Lymphoma • CNS Disorders • Diabetes • Endocrine Disorders • Fatigue • Graft versus Host Disease • Hematological Malignancies • Hepatology • Hodgkin Lymphoma • Immunology • Lymphoma • Melanoma • Metabolic Disorders • Oncology • Solid Tumor • Transplantation • Type 1 Diabetes Mellitus

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 • Classical Hodgkin Lymphoma • Endocrine Disorders • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Hepatology • Hodgkin Lymphoma • Immunology • Lymphoma • Melanoma • Oncology • Pneumonia • Solid Tumor • LAG3

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 • B Cell Lymphoma • Classical Hodgkin Lymphoma • Constipation • Cough • Diffuse Large B Cell Lymphoma • Endocrine Disorders • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pruritus • Respiratory Diseases • Richter's Syndrome

Coformulation of favezelimab and pembrolizumab as neoadjuvant therapy for resectable cutaneous squamous cell carcinoma (cSCC): results from cohort A of the phase 2 KeyForm-010 study (SITC 2025) - P2 | "All participants provided written informed consent before enrollment. Abstract 1305 Table 1View inline•Open as popupEfficacy resultsAbstract 1305 Table 2View inline•Open as popupSummary of AEs during neoadjuvant phasea"

Clinical • Late-breaking abstract • P2 data • Head and Neck Cancer • Melanoma • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • PD-L1

First-line pembrolizumab-based regimens for advanced clear cell renal cell carcinoma: KEYMAKER-U03 substudy 03A (ESMO 2025) - P1/2 | "Methods Adults with advanced ccRCC and no prior systemic therapy were randomized 2:1 to open investigational arms or the reference (ref): coformulated quavonlimab (qmab; anti-CTLA-4)/pembro + lenvatinib (lenva; VEGFR-TKI); coformulated favezelimab (fave; anti-LAG-3)/pembro + lenva; pembro + lenva + belzutifan (bel; HIF-2α inhibitor); coformulated vibostolimab (vibo; anti-TIGIT)/pembro + bel; ref, pembro + lenva. Other regimens did not show improved ORR and PFS compared with pembrolizumab + lenvatinib, yet the duration of follow-up was insufficient to detect long-term contributions to OS. Safety profiles were consistent with the profiles of the individual drugs in each regimen."

Clinical • Late-breaking abstract • Metastases • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • EPAS1 • TIGIT

Novel pembrolizumab-based treatments as first-line therapy in advanced clear cell renal cell carcinoma: Substudy 03A of the open-label, umbrella platform, phase I/II KEYMAKER-U03 trial. (PubMed, Ann Oncol) - P1/2 | "Observed efficacy and safety of pembro plus lenva were confirmatory of prior observations for this combination. ORR was similar to reference for pembro plus lenva plus bel and qmab/pembro plus lenva, but not the other investigative arms. Further investigation of pembro plus lenva plus bel and qmab/pembro plus lenva versus pembro plus lenva is ongoing in the phase 3 LITESPARK-012 study."

Journal • P1/2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

First-line pembrolizumab alone or with investigational agents for advanced melanoma: Updated results from the phase I/II KEYMAKER-U02 substudy 02B (ESMO 2025) - P1/2 | "Background Prior analysis of KEYMAKER-U02 substudy 02B (NCT04305054) showed promising activity for first-line vibostolimab (vibo) + pembrolizumab (pembro) and coformulated quavonlimab (qmab)/pembro in advanced melanoma. Manageable safety was observed across the first 4 arms (vibo + pembro, pembro alone, qmab/pembro; qmab/pembro + lenvatinib [len]). Updated results are presented, including from 2 previously unreported arms: coformulated favezelimab (fave; anti–LAG-3)/pembro and fave/pembro + all-trans retinoic acid (ATRA)...Conclusions Safety was manageable across arms. Moderate antitumor activity was observed with fave/pembro (arm 5); no additional benefit was observed with combining ATRA with fave/pembro (arm 6)."

Clinical • Metastases • P1/2 data • Melanoma • Oncology • Solid Tumor

Estimating efficacy of favezelimab plus pembrolizumab relative to pembrolizumab in anti-PD-1-refractory Hodgkin lymphoma. (PubMed, Blood Adv) - P1/2, P2 | "Favezelimab plus pembrolizumab had a higher response rate and greater reduction in tumor burden vs pembrolizumab alone in anti-PD-1-refractory classical Hodgkin lymphoma, suggesting favezelimab contributed substantially to efficacy in MK-4280-003. NCT03598608, NCT02453594."

Journal • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

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

FINAL SAFETY ANALYSIS IN PARTICIPANTS WITH HEMATOLOGIC MALIGNANCIES WHO RECEIVED ALLOGENEIC STEM CELL TRANSPLANT AFTER PEMBROLIZUMAB THERAPY (ICML 2025) - P1, P1/2, P2, P3 | " Data were pooled from 10 phase 1–3 studies (KEYNOTE-A33 [NCT04317066], KEYNOTE-013 [NCT01953692], KEYNOTE-155 [NCT02684617], KEYNOTE-051 [NCT02332668], KEYNOTE-B68 [NCT04875195], KEYNOTE-087 [NCT02453594], KEYNOTE-170 [NCT02576990], KEYNOTE-183 [NCT02576977], KEYNOTE-204 [NCT02684292], and MK4280-003 [NCT03598608]). The inclusion of additional pts in this analysis revealed comparable rates of acute and chronic GVHD, OS, and TRM compared to previous studies and historical benchmarks, thus, reinforcing the role of allo-SCT as a viable salvage option post-anti–PD-1 therapy."

Clinical • Hematological Malignancies • Lymphoma • Oncology

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