boserolimab (MK-5890) / Merck (MSD), Novartis - LARVOL DELTA

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

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

A Clinical Study of Boserolimab (MK-5890) With Pembrolizumab and Chemotherapy in People With Early Triple-Negative Breast Cancer (MK-5890-003) (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Merck Sharp & Dohme LLC | N=100 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

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

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

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-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 Clinical Study of Boserolimab (MK-5890) With Pembrolizumab and Chemotherapy in People With Early Triple-Negative Breast Cancer (MK-5890-003) (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

A Clinical Study of Boserolimab (MK-5890) With Pembrolizumab and Chemotherapy in People With Early Triple-Negative Breast Cancer (MK-5890-003) (clinicaltrials.gov) - P2 | N=100 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P2 trial • Breast Cancer • Oncology • 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 | 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

Study of Boserolimab (MK-5890) as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Adults With Advanced Solid Tumors (MK-5890-001) (clinicaltrials.gov) - P1 | N=184 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • 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 | 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

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

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

Phase 1 evaluation of triple therapy with boserolimab (anti-CD27 agonist), pembrolizumab, and chemotherapy in patients with triple-negative breast cancer (TNBC) with PD-L1 combined positive score (CPS) <10: Safety, antitumor activity, and association between biomarkers and response (AACR 2024) - P1 | "Pts received boserolimab 30 mg IV Q6W plus pembro 400 mg IV Q6W for 18 cycles plus nab-paclitaxel 100 mg/m2 (3 weeks on [days 1, 8, and 15]/1 week off). In pts with TNBC and tumors expressing PD-L1 at the cutoff of CPS <10, triple therapy with boserolimab, pembro, and chemo had acceptable safety and showed preliminary evidence of antitumor activity regardless of baseline TcellinfGEP expression or TMB status."

Biomarker • Clinical • IO biomarker • P1 data • Tumor mutational burden • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD27 • PD-L1 • TMB

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

Epitope mapping of monoclonal antibodies: a comprehensive comparison of different technologies. (PubMed, MAbs) - "Here, we evaluated six widely used alternative methods for epitope identification (peptide array, alanine scan, domain exchange, hydrogen-deuterium exchange, chemical cross-linking, and hydroxyl radical footprinting) in five antibody-antigen combinations (pembrolizumab+PD1, nivolumab+PD1, ipilimumab+CTLA4, tremelimumab+CTLA4, and MK-5890+CD27). The advantages and disadvantages of each technique are demonstrated by our data and practical advice on when and how to apply specific epitope mapping techniques during the drug development process is provided. Our results suggest chemical cross-linking most accurately identifies the epitope as defined by crystallography."

Journal • CD27 • CTLA4

Management of Immune Checkpoint Inhibitor Mediated Myocarditis (AHA 2023) - "She had just completed her 3rd round of carboplatin/pemetrexed/pembrolizumab/MK-5890 chemotherapy. Additionally, symptomatic myocarditis treatment should be started. Reinitiating ICI therapy should ultimately be done with shared decision making."

Checkpoint inhibition • Cardiovascular • Inflammation • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Solid Tumor • Ventricular Tachycardia

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

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 | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

KEYNOTE-B99: Phase 2 Study of Pembrolizumab Plus Investigational Agents Combined With Chemotherapy as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer (ES-SCLC) (ESMO-IO 2021) - P2 | "KEYNOTE-B99 (NCT04924101) is a randomized, phase 2, rolling-arm, multicenter open-label study evaluating pembrolizumab plus EP chemotherapy combined with either MK-4830 (an anti-ILT4 antibody), MK-5890 (an anti-CD27 antibody), or lenvatinib as first-line therapy for ES-SCLC...All patients receive 4 cycles of chemotherapy Q3W (etoposide 100 mg/m 2 for 3 days plus cisplatin 75 mg/m 2 or carboplatin area under the concentration-time curve [AUC] 5 mg/mL/min)...Legal entity responsible for the study Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Funding Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA."

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

Study of MK-5890 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Adults With Advanced Solid Tumors (MK-5890-001) (clinicaltrials.gov) - P1 | N=202 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Monotherapy • Breast Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

KEYNOTE-01A: 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 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | N=270 ➔ 360

Combination therapy • Enrollment change • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

KEYNOTE-01C: 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=135 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Preclinical characterization and clinical translation of pharmacodynamic markers for MK-5890: a human CD27 activating antibody for cancer immunotherapy. (PubMed, J Immunother Cancer) - "MK-5890 is a novel CD27 agonistic antibody with the potential to complement the activity of PD-1 checkpoint inhibition in cancer immunotherapy and is currently undergoing clinical evaluation."

IO biomarker • Journal • PK/PD data • Preclinical • Immune Modulation • Inflammation • Oncology • CCL4 • CD27 • CD70 • CD8 • TNFA