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

KEYMAKER-U01 Substudy 2: Efficacy and Safety Study of Pembrolizumab (MK-3475) When Used With Investigational Agents in Treatment-naïve Participants With Anti-programmed Cell Death Receptor Ligand 1 (PD-L1) Positive Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01B/KEYMAKER-U01B) (clinicaltrials.gov) - P2 | N=102 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

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

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

Pembrolizumab (pembro) plus investigational agents as first-line therapy for treatment-naive PD-L1–positive advanced non–small-cell lung cancer (NSCLC): Results from KEYMAKER-U01 substudy 01B (ESMO 2025) - P, P2 | "Grade ≥3 treatment-related AEs occurred in 11 pts (18.3%) in arm 1 and in 3 pts (7.5%) in arm 2. Conclusions Findings from KEYMAKER-U01 substudy 01B demonstrate that the anti-ILT4 mAb MK-4830 and anti-ILT3 mAb MK-0482 each in combination with pembro have antitumor activity similar to that previously observed with pembro alone and a manageable AE profile in treatment-naive pts with advanced NSCLC."

Clinical • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1

KEYMAKER-U02 Substudy 02C: Substudy 02C: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Stage III Melanoma Who Are Candidates for Neoadjuvant Therapy (MK-3475-02C/KEYMAKER-U02) (clinicaltrials.gov) - P1/2 | N=146 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed | N=90 ➔ 146

Enrollment change • Trial completion • Melanoma • Oncology • 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=200 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Sep 2028 ➔ Apr 2029

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

KEYMAKER-U02 Substudy 02C: Substudy 02C: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Stage III Melanoma Who Are Candidates for Neoadjuvant Therapy (MK-3475-02C/KEYMAKER-U02) (clinicaltrials.gov) - P1/2 | N=90 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Apr 2030 ➔ Oct 2025 | Trial primary completion date: Apr 2030 ➔ Oct 2025

Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Efficacy and Safety of Pembrolizumab Plus Investigational Agents in Combination With Chemotherapy as First-Line Treatment in Extensive-Stage Small Cell Lung Cancer (ES-SCLC) (MK-3475-B99/ KEYNOTE-B99) (clinicaltrials.gov) - P2 | N=126 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

KEYMAKER-U01 Substudy 3: Efficacy and Safety Study of Pembrolizumab (MK-3475) When Used With Investigational Agents in Participants With Advanced Non-small Cell Lung Cancer (NSCLC), Previously Treated With Anti-programmed Cell Death Receptor Ligand 1 (PD-L1) Therapy (MK-3475-01C/KEYMAKER-U01C) (clinicaltrials.gov) - P2 | N=128 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed | Trial completion date: Feb 2032 ➔ May 2025 | Trial primary completion date: Feb 2032 ➔ Apr 2025

Trial completion • Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Circulating tumor DNA (ctDNA) monitoring in participants (pts) with ovarian cancer treated with neoadjuvant pembrolizumab (pembro) + chemotherapy (chemo) ± anti–immunoglobulin-like transcript 4 (ILT4) monoclonal antibody MK-4830. (ASCO 2025) - P1, P2 | "Pts were randomly assigned 1:1 to receive neoadjuvant MK-4830 800 mg + pembro 200 mg + chemo (paclitaxel 175 mg/m2 and carboplatin AUC 5-6) (arm 1) or pembro + chemo (arm 2) IV Q3W for 3 cycles. Pts underwent interval debulking surgery followed by 3 cycles of adjuvant therapy with the neoadjuvant regimen; adjuvant bevacizumab IV Q3W was permitted... In pts with HGSOC, reductions in ctDNA were similar between neoadjuvant/adjuvant MK-4830 + pembro + chemo vs pembro + chemo. Real-time tumor-informed ctDNA testing may be feasibly incorporated into future clinical trials as a surrogate outcome to evaluate response. The safety profile of MK-4830 + pembro + chemo was comparable to pembro + chemo."

Circulating tumor DNA • Clinical • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor

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

Evaluation of Co-formulated Pembrolizumab/Quavonlimab (MK-1308A) Versus Other Treatments in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Cancer (CRC) (MK-1308A-008/KEYSTEP-008) (clinicaltrials.gov) - P2 | N=302 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Jun 2027 ➔ Apr 2026 | Trial primary completion date: Jun 2026 ➔ May 2025

dMMR • Mismatch repair • MSI-H • Trial completion date • Trial primary completion date • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor • MSI

Efficacy and Safety of Pembrolizumab Plus Investigational Agents in Combination With Chemotherapy as First-Line Treatment in Extensive-Stage Small Cell Lung Cancer (ES-SCLC) (MK-3475-B99/ KEYNOTE-B99) (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Jul 2026 ➔ Jun 2025 | Trial primary completion date: Jul 2026 ➔ Jun 2025

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

KEYMAKER-U06 substudy 06A: A Study of Combination Therapies With or Without Pembrolizumab (MK-3475) and/or Chemotherapy in Participants With Advanced Esophageal Cancer (MK-3475-06A) (clinicaltrials.gov) - P1/2 | N=120 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Sep 2026 ➔ Nov 2025 | Trial primary completion date: Mar 2025 ➔ Nov 2025

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

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=370 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Sep 2025 ➔ May 2026 | Trial primary completion date: Sep 2025 ➔ May 2026

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

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 • Metastases • P1 data • Breast Cancer • Epithelial Ovarian Cancer • Mesothelioma • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer

KEYMAKER-U01 Substudy 01A: Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A) (clinicaltrials.gov) - P1/2 | N=450 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Feb 2039 ➔ Feb 2032 | Trial primary completion date: Feb 2039 ➔ Feb 2032

Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ERBB3

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

Evaluation of Co-formulated Pembrolizumab/Quavonlimab (MK-1308A) Versus Other Treatments in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Cancer (CRC) (MK-1308A-008/KEYSTEP-008) (clinicaltrials.gov) - P2 | N=320 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Nov 2025 ➔ Jun 2027 | Trial primary completion date: Oct 2025 ➔ Jun 2026

Metastases • Mismatch repair • Trial completion date • Trial primary completion date • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor • MSI

Phase I/II open-label, umbrella platform designed study of investigational agents with or without pembrolizumab and/or chemotherapy in patients with advanced esophageal cancer previously treated with a PD-(L)1 inhibitor: KEYMAKER-U06 substudy 06B (ESMO Asia 2024) - P1/2 | "Patients will be assigned to treatment arms 1 or 4: investigator's choice of chemotherapy (paclitaxel 80-100 mg/m 2 IV days 1, 8, and 15 of every 28-day cycle or irinotecan 180 mg/m 2 day 1 of every 14-day cycle) (arm 1; ≥30 patients) or sacituzumab tirumotecan (also known as MK-2870/SKB264; trophoblast antigen 2–directed antibody drug conjugate) 4 mg/kg IV days 1, 15, and 29 of every 42-day cycle (arm 4; n ∼40 patients). Arms 2 (pembrolizumab 200 mg IV Q3W + MK-4830 800 mg IV Q3W + chemotherapy) and 3 (pembrolizumab + MK-4830 + lenvatinib 20 mg PO QD) are no longer enrolling. The primary end point is ORR per RECIST v1.1 by BICR in the efficacy phase (random assignment between arms 1 and 4); secondary end points are PFS and DOR per RECIST v1.1 by BICR, OS, safety, and tolerability. Enrollment is ongoing in arms 1 and 4."

Clinical • Metastases • P1/2 data • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Oncology • Squamous Cell Carcinoma

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 | Active, not recruiting ➔ Recruiting | N=80 ➔ 110 | Trial completion date: Nov 2026 ➔ Nov 2029 | Trial primary completion date: Nov 2026 ➔ May 2026

Combination therapy • Enrollment change • Enrollment open • Monotherapy • Trial completion date • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Pembrolizumab With Chemotherapy and MK-4830 for Treating Participants With Ovarian Cancer (MK-4830-002) (clinicaltrials.gov) - P2 | N=160 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor

KEYMAKER-U01 Substudy 01A: Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A) (clinicaltrials.gov) - P1/2 | N=450 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Recruiting

Enrollment open • Metastases • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

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: Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A) (clinicaltrials.gov) - P1/2 | N=450 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Phase classification: P2 ➔ P1/2

Metastases • Phase classification • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor