MK-4830 / Merck (MSD), Agenus, Ligand - LARVOL DELTA

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

Results from KEYNOTE-B99: Phase 2 study of first-line (1L) pembrolizumab (pembro) plus investigational agents and chemotherapy (chemo) for extensive-stage small-cell lung cancer (ES-SCLC) (AACR 2024) - P2 | "All pts received pembro 200 mg Q3W (35 cycles) + etoposide 100 mg/m2 Q3W and cisplatin 75 mg/m2 Q3W or carboplatin AUC 5 mg/mL/min Q3W (4 cycles). 1L ES-SCLC treatment with pembro + EP and MK-4830, boserolimab, or lenvatinib was associated with similar antitumor activity as in KEYNOTE-604 with pembro + EP. No new safety signals were identified."

Clinical • P2 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CD27

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

KEYMAKER-U01 substudy 01A: Investigational agents + pembrolizumab (pembro) and chemotherapy (chemo) in untreated stage IV non-small cell lung cancer (NSCLC) (ESMO 2025) - P1/2 | "Methods Adults with untreated confirmed stage IV NSCLC, measurable disease per RECIST v1.1, and no EGFR , ALK , or ROS1 mutations received pembro 200 mg + chemo (carboplatin + paclitaxel [squamous] or pemetrexed [nonsquamous]) Q3W with vibostolimab IV 200 mg Q3W, boserolimab IV 30 mg Q6W, MK-4830 IV 800 mg Q3W, or MK-0482 IV 750 mg Q3W for 4 cycles, followed by pembro with the same investigational agent (+ pemetrexed for nonsquamous) for 35 total cycles or until PD or unacceptable toxicity. a Investigator-assessed per RECIST v1.1. Conclusions Pembro and chemo + investigational agents demonstrated antitumor activity similar to previous reports for pembro and chemo and manageable AEs in untreated stage IV squamous or nonsquamous NSCLC."

IO biomarker • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CD27 • EGFR • ROS1 • TIGIT

KEYMAKER-U01 substudy 01A: Phase 1/2 study of pembrolizumab plus ifinatamab deruxtecan (I-DXd) or patritumab deruxtecan (HER3-DXd) with or without chemotherapy in untreated stage IV non–small-cell lung cancer. (ASCO 2025) - P1/2 | "KEYMAKER-U01 substudy 01A (NCT04165070) is a phase 1/2, two-part, rolling arm, open-label study assessing the efficacy and safety of pembrolizumab plus an investigational agent (part A: vibostolimab, boserolimab, MK-4830, and MK-0482; part B: I-DXd and HER3-DXd), with or without chemotherapy in untreated stage IV NSCLC...In Arms 5 and 6, participants will receive I-DXd plus pembrolizumab 200 mg Q3W (Arm 5) or I-DXd plus pembrolizumab with 4 cycles of carboplatin area under the curve 5 or 6 mg/ml/min (Arm 6); I-DXd dose will be at 8mg/kg...The primary endpoint is incidence of dose-limiting toxicities until the start of cycle 2, and AEs and treatment discontinuations due to AEs until 40 days after last treatment (90 days for serious AEs); secondary endpoints include ORR and DOR, both per RECIST v1.1 by BICR, and pharmacokinetic parameters, including maximum concentration (Cmax) and maximum trough concentration (Ctrough) of I-DXd and HER3-DXd. Enrollment will be..."

IO biomarker • Metastases • P1/2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ERBB3 • HER-2 • ROS1

KEYSTEP-008: Pembrolizumab (pembro)-based combinations for microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC). (ASCO-GI 2026) - P2 | " Adults with stage IV colorectal adenocarcinoma, locally confirmed MSI-H/dMMR status and ECOG PS 0 or 1 were randomized 1:1 (cohort A) to coformulated quavonlimab (anti–CTLA-4; Qmab)/pembro (25 mg/400 mg) IV Q6W or pembro 400 mg IV Q6W or 1:1:1:1:1 (cohort B) to Qmab/pembro (25 mg/400 mg) IV Q6W, MK-4830 (anti-ILT4) 800 mg + pembro 200 mg IV Q3W, coformulated favezelimab (anti−LAG-3; fave)/pembro (800 mg/200 mg) IV Q3W, coformulated vibostolimab (anti-TIGIT; vibo)/pembro (200 mg/200 mg) IV Q3W, or pembro 400 mg IV Q6W. Pembro-based combinations evaluated in this study showed numerically higher ORR vs pembro alone, but the absolute improvement was modest, especially in the 1L setting. Despite manageable safety, these results do not support further clinical development of these combinations in pts with MSI-H/dMMR mCRC. NR, not reached."

dMMR • Metastases • Mismatch repair • MSI-H • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MSI • TIGIT

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

Results from KEYMAKER-U01 substudy 3: a phase 2 umbrella study of pembrolizumab plus investigational agents in patients with non-small-cell lung cancer (NSCLC) previously treated with anti-PD-(L)1 therapy (AACR 2024) - P | "In the KEYMAKER-U01 substudy 3 evaluating novel treatment combinations of pembrolizumab plus boserolimab, MK-4830, or MK-0482 in patients with NSCLC that progressed on/after platinum-based chemotherapy and anti-PD-(L)1 therapy, modest antitumor activity was observed with all 3 treatment combinations. No new safety signals were observed for the treatment combinations investigated."

Clinical • P2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD27

Results from a phase 1 study of the anti-immunoglobulin-like transcript 4 (ILT4) monoclonal antibody MK-4830 plus pembrolizumab in patients with previously treated advanced solid tumors (AACR 2024) - P1 | "In pts with select previously treated advanced or metastatic solid tumors, MK-4830 + pembro had a manageable AE profile but no significant antitumor activity beyond that historically observed with pembro monotherapy. Other treatment options must be explored for these difficult-to-treat tumors."

Clinical • First-in-human • IO biomarker • Metastases • P1 data • Brain Cancer • CNS Tumor • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Phase 1 study of the anti-immunoglobulin-like transcript 4 (ILT4) monoclonal antibody MK-4830 plus pembrolizumab plus chemotherapy in patients with advanced solid tumors (AACR 2025) - P1 | "All pts received MK-4830 800 mg plus pembro 200 mg IV Q3W for 35 cycles plus chemo (cohort J: paclitaxel 80 mg/m2 [days 1, 8, and 15 Q3W] or docetaxel 75 mg/m2 Q3W or 25 mg/m2 weekly; cohort K: paclitaxel 90 mg/m2 [days 1, 8, and 15 Q4W]; cohort L: pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 Q3W for 6 cycles or carboplatin AUC 5-6 Q3W for 4 cycles). In pts with select advanced solid tumors, the safety profile observed with MK-4830 plus pembro plus chemo was manageable and consistent with that for each individual therapy. Modest antitumor activity was observed with the addition of MK-4830 to pembro plus chemo. Investigation of other therapies in these difficult-to-treat tumor types is warranted."

Clinical • First-in-human • Metastases • P1 data • Breast Cancer • Epithelial Ovarian Cancer • Mesothelioma • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer

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

KEYMAKER-U06 substudy 06B: A Study to Evaluate Investigational Agents With or Without Pembrolizumab (MK-3475) in Participants With Advanced Esophageal Cancer Previously Exposed to Programmed Cell Death 1 Protein (PD-1)/ Programmed Cell Death Ligand 1 (PD-L1) Treatment (MK-3475-06B) (clinicaltrials.gov) - P1/2 | N=230 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial primary completion date: Nov 2026 ➔ Jun 2027

Trial primary completion date • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma

Phase 1 study of the anti-immunoglobulin-like transcript 4 (ILT4) monoclonal antibody MK-4830 plus pembrolizumab in patients with previously untreated advanced head and neck squamous cell carcinoma (HNSCC) or non-small cell lung cancer (NSCLC) (AACR 2024) - P1 | "In pts with advanced HNSCC or NSCLC, first-line MK-4830 + pembro had a manageable AE profile with modest antitumor activity. Consistent with what was previously observed for pembro alone, a trend was observed between PD-L1 TPS and response to MK-4830 + pembro in pts with NSCLC."

Clinical • First-in-human • IO biomarker • Metastases • P1 data • Tumor mutational burden • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • TMB

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

Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4830-001) (clinicaltrials.gov) - P1 | N=70 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | Trial completion date: Jul 2022 ➔ Sep 2021 | Trial primary completion date: Jul 2022 ➔ Sep 2021

Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • HER-2

Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4830-001) (clinicaltrials.gov) - P1 | N=70 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • HER-2

Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4830-001) (clinicaltrials.gov) - P1 | N=470 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Monotherapy • Trial completion • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Glioblastoma • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • HER-2

Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4830-001) (clinicaltrials.gov) - P1 | N=70 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | Trial completion date: Sep 2021 ➔ Nov 2022 | Trial primary completion date: Sep 2021 ➔ Nov 2022

Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • HER-2

Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4830-001) (clinicaltrials.gov) - P1 | N=410 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | N=290 ➔ 410

Enrollment change • Monotherapy • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • HER-2

Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4830-001) (clinicaltrials.gov) - P1 | N=442 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Nov 2024 ➔ Nov 2025 | Trial primary completion date: Nov 2024 ➔ Nov 2025

Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • HER-2

Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4830-001) (clinicaltrials.gov) - P1 | N=442 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • HER-2

Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4830-001) (clinicaltrials.gov) - P1 | N=270 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | N=70 ➔ 270 | Trial completion date: Nov 2022 ➔ Jun 2023 | Trial primary completion date: Nov 2022 ➔ Jun 2023

Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • HER-2

Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4830-001) (clinicaltrials.gov) - P1 | N=70 | Not yet recruiting | Sponsor: Merck Sharp & Dohme Corp.

Monotherapy • New P1 trial • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Mesothelioma • Non Small Cell Lung Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • HER-2

Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4830-001) (clinicaltrials.gov) - P1 | N=290 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | Trial completion date: Jul 2023 ➔ Nov 2024 | Trial primary completion date: Jul 2023 ➔ Nov 2024

Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • HER-2

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