MK-0482 / Merck (MSD) - 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

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-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

A Study of MK-0482 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-0482-001) (clinicaltrials.gov) - P1 | N=222 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Brain Cancer • Breast Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ALK • EGFR • MGMT • ROS1

Phase 1 study of the anti–immunoglobulin-like transcript 3 (ILT3) monoclonal antibody (mAb) MK-0482 + pembrolizumab (pembro) + paclitaxel for previously untreated advanced triple negative breast cancer (TNBC). (ASCO 2025) - P1 | "In pts with advanced TNBC, MK-0482 + pembro + paclitaxel had a manageable safety profile, but showed no difference in efficacy compared to that historically observed with pembro + paclitaxel or gemcitabine-carboplatin. Therefore, further investigation of this combination will not be pursued for advanced TNBC."

IO biomarker • Metastases • P1 data • Breast Cancer • Neutropenia • Oncology • Solid Tumor • Triple Negative Breast Cancer • IL3

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

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

A Study of MK-0482 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-0482-001) (clinicaltrials.gov) - P1 | N=230 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Feb 2025 ➔ Jun 2025 | Trial primary completion date: Feb 2025 ➔ Jun 2025

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ALK • EGFR • MGMT • ROS1

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-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

Phase 1 study of anti–immunoglobulin-like transcript 3 (ILT3) monoclonal antibody MK-0482 + pembrolizumab + gemcitabine + nab-paclitaxel (Gem/Nab-P) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC). (ASCO 2024) - P1 | "MK-0482 + pembrolizumab + Gem/Nab-P showed a manageable AE profile in patients with treatment-naive mPDAC, which was generally consistent with the combined safety profiles of pembrolizumab-based immunotherapy and Gem/Nab-P, respectively. The 4-drug combination showed increased clinical efficacy compared with that historically observed for chemotherapy regimens. Further evaluation is needed to confirm the clinical activities observed."

Clinical • IO biomarker • Metastases • P1 data • Anemia • Endocrine Disorders • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Hematological Disorders • Hepatology • Immunology • Neutropenia • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Phase 1 study of anti–immunoglobulin-like transcript 3 (ILT3) monoclonal antibody (mAb) MK-0482 + pembrolizumab (pembro) in patients with recurrent inoperable glioblastoma (GBM). (ASCO 2024) - P1 | "All patients had previously received systemic therapy: 24 of 25 (96%) received prior temozolomide and 3 of 25 (12%) received prior glasdegib. MK-0482 + pembro had a manageable AE profile with modest antitumor activity in patients with recurrent inoperable GBM."

Clinical • P1 data • Brain Cancer • CNS Tumor • Endocrine Disorders • Fatigue • Glioblastoma • Hepatology • Musculoskeletal Pain • Oncology • Pancreatitis • Solid Tumor • IDH1 • IL3

PBI-MST-01 (NCT04541108) Substudy MSD-03: Intratumoral Microdosing of Pembrolizumab Alone and With MK-0482 or MK-4830 in HNSCC or STS (clinicaltrials.gov) - P1 | N=13 | Completed | Sponsor: Presage Biosciences

New P1 trial • Head and Neck Cancer • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD163 • CD8 • GZMB • IFNG

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

A Study of MK-0482 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-0482-001) (clinicaltrials.gov) - P1 | N=230 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Phase classification: P1b ➔ P1

Combination therapy • Metastases • Monotherapy • Phase classification • Brain Cancer • Breast Cancer • Gastrointestinal Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ALK • EGFR • MGMT • ROS1

KEYMAKER-U01 Substudy 1: Efficacy and Safety Study of Pembrolizumab (MK-3475) Plus Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A) (clinicaltrials.gov) - P2 | N=360 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Feb 2032 ➔ Feb 2039 | Trial primary completion date: Feb 2032 ➔ Feb 2039

Combination therapy • Metastases • 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

A Study to Evaluate MK-0482 for Relapsed/Refractory Acute Myeloid Leukemia (AML) or Chronic Myelomonocytic Leukemia (CMML) (MK-0482-002) (clinicaltrials.gov) - P1 | N=12 | Terminated | Sponsor: Merck Sharp & Dohme LLC | N=35 ➔ 12 | Active, not recruiting ➔ Terminated; Business Reasons

Enrollment change • Trial termination • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

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=120 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Feb 2032 ➔ Sep 2025 | Trial primary completion date: Feb 2032 ➔ Sep 2025

Combination therapy • Metastases • 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 • PD-L1

A Study to Evaluate MK-0482 for Relapsed/Refractory Acute Myeloid Leukemia (AML) or Chronic Myelomonocytic Leukemia (CMML) (MK-0482-002) (clinicaltrials.gov) - P1 | N=35 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Phase classification: P1b ➔ P1 | Trial completion date: Aug 2025 ➔ Dec 2023 | Trial primary completion date: Aug 2025 ➔ Dec 2023

Phase classification • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

KEYMAKER-U01 Substudy 1: Efficacy and Safety Study of Pembrolizumab (MK-3475) Plus Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A) (clinicaltrials.gov) - P2 | N=360 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • 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-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=120 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • 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

Evaluation of the effects of pembrolizumab alone and in combination(s) with MDSC-targeting agents MK-0482 and MK-4830 on the native cancer patient TME via functional spatial profiling (CIVO®) (SITC 2023) - "Conclusions Functional spatial profiling of the cancer patient TME following multiplexed intratumoral CIVO microinjection enabled in-depth, safe, and efficient side-by-side evaluation of pembrolizumab alone and in combination with MK-0482 or MK-4830. Further study to determine whether the localized TME responses to CIVO predict the therapeutic benefit of checkpoint inhibitor combinations in different patient subsets is warranted."

Clinical • IO biomarker • Myeloid-derived suppressor cells • Tumor mutational burden • Head and Neck Cancer • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Synovial Sarcoma • CD163 • TMB

A Study to Evaluate MK-0482 for Relapsed/Refractory Acute Myeloid Leukemia (AML) or Chronic Myelomonocytic Leukemia (CMML) (MK-0482-002) (clinicaltrials.gov) - P1b | N=35 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Neutropenia • Oncology

A Study of MK-0482 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-0482-001) (clinicaltrials.gov) - P1b | N=230 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Monotherapy • Brain Cancer • Breast Cancer • Gastrointestinal Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ALK • EGFR • MGMT • ROS1