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

KEYMAKER-U04 substudy 04B: First-line (1L) enfortumab vedotin (EV) plus pembrolizumab (pembro)-based immune checkpoint inhibitor (ICI) combinations for advanced urothelial cancer (UC). (ASCO-GU 2026) - P1/2 | " Adult pts without prior systemic therapy for la/mUC and an ECOG PS of 0-1 were randomized 1:1:1 to EV + coformulated favezelimab (fave; anti–LAG3)/pembro 800 mg/200 mg (arm A), EV + coformulated vibostolimab (vibo; anti-TIGIT)/pembro 200 mg/200 mg (arm B), and EV + pembro 200 mg (arm C). In pts with la/mUC, the addition of LAG3- or TIGIT-targeted ICIs to EV + pembro did not have a clinically significant impact on efficacy. No new safety signals were identified. Incidence of certain immune-mediated AEs was higher with pembro-containing coformulations compared to EV + pembro."

Checkpoint inhibition • Clinical • Metastases • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • 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

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 | N=134 | Not yet recruiting | Sponsor: Merck Sharp & Dohme Corp.

New P1 trial • New P1/2 trial • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Classical Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hodgkin Lymphoma • Non-Hodgkin’s Lymphoma

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 • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Classical Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • 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: Dec 2026 ➔ Oct 2027 | Trial primary completion date: Dec 2026 ➔ Oct 2027

Trial completion date • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Classical Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • 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 | 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 Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s 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=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

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=134 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | Trial completion date: Dec 2025 ➔ Aug 2026 | Trial primary completion date: Dec 2025 ➔ Aug 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 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: Apr 2028 ➔ Oct 2028 | Trial primary completion date: Apr 2028 ➔ Oct 2028

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

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

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 • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Classical Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s 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) - 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

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 Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

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

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 • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Classical Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • 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=134 | Not yet recruiting | Sponsor: Merck Sharp & Dohme Corp. | Phase classification: P1 ➔ P1/2

Phase classification • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Classical Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hodgkin Lymphoma • Non-Hodgkin’s Lymphoma

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 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | Not yet recruiting ➔ Recruiting

Biomarker • Enrollment open • 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=288 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | N=192 ➔ 288

Biomarker • Enrollment change • Tumor mutational burden • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer • 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=134 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | Not yet recruiting ➔ Recruiting

Enrollment open • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Classical Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • 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=134 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | Trial primary completion date: Jul 2025 ➔ Nov 2025

Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Classical Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s 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 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | Trial completion date: Jan 2023 ➔ Feb 2025 | Trial primary completion date: Jan 2023 ➔ Feb 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

KEYMAKER-U03 substudy 03B: Novel investigative regimens for previously treated advanced clear cell renal cell carcinoma (ccRCC). (ASCO-GU 2026) - P1/2 | " Adults with confirmed ccRCC and disease progression on or after PD-(L)1 inhibitor and VEGF-TKI were randomly assigned to open arms: pembrolizumab (pembro)/quavonlimab (qmab; anti–CTLA-4), pembro/favezelimab (fave; anti-LAG3), pembro + MK-4830 (anti-ILT4), pembro + belzutifan (bel; HIF-2α inhibitor), bel + lenvatinib (lenva; VEGF-TKI), and pembro + lenva. Bel + lenva continued to demonstrate the highest antitumor activity followed by pembro + lenva. Pembro + bel activity was similar to historical bel monotherapy. In the small pembro/qmab cohort, median OS was not reached."

Metastases • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • EPAS1

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