assignment

Recruiting

Phase 1b/2 Umbrella Study of MK-1084 and Combination Therapy in Patients With Previously Treated Advanced or Metastatic KRAS G12C-Mutated Nonsquamous NSCLC

Trial ID: 2024-512248-47-00
Protocol: MK-3475-01F
Sponsor: Merck Sharp & Dohme LLC

Trial statistics

science

test molecules

location_city

research sites

public

countries

medical_information

disease

person_search

investigators

handshake

vendors

Diseases & Conditions

Non-small cell lung cancer

Objectives

The primary objectives of this study are to evaluate the safety and tolerability of investigational agent combinations and to determine the objective response rate (ORR) as assessed by blinded independent central review (BICR) using RECIST 1.1 criteria in participants with advanced or metastatic non-small cell lung cancer (NSCLC) harboring KRAS G12C mutations. Secondary objectives include:

Evaluation of duration of response (DOR) per RECIST 1.1 as assessed by BICR.
Assessment of progression-free survival (PFS) per RECIST 1.1 as assessed by BICR during the Phase 2 portion of the study.
Characterization of the pharmacokinetics (PK) of the investigational agent combinations.

Participants

This clinical trial involves 133 participants diagnosed with advanced or metastatic non-small cell lung cancer. The study population consists of both male and female patients within the age ranges of 18-44 and 45-64 years. Eligible individuals must have a histologically or cytologically confirmed diagnosis of non-squamous disease. A required characteristic is the presence of a KRAS G12C mutation identified in tumor tissue or circulating tumor DNA. Participants must have documented disease progression following treatment with PD-1/PD-L1 inhibitors and platinum-based chemotherapy. The protocol requires the provision of archival tumor tissue or a new biopsy from a non-irradiated lesion. Individuals with HIV infection are permitted if the condition is well-controlled through antiretroviral therapy. The objectives of the study are:

To evaluate the safety and tolerability of investigational agent combinations
To evaluate overall response rate per RECIST 1.1 as assessed by blinded independent central review

Plans and Procedures

This Phase 1b/2 umbrella study utilizes rolling arms to evaluate investigational agent combinations in participants with advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) harboring KRAS G12C mutations. The primary objectives are to assess the safety, tolerability, and objective response rate (ORR) as determined by blinded independent central review (BICR). The study investigates several therapeutic agents, including MK-1084, patritumab deruxtecan, sacituzumab tirumotecan, and cetuximab. Secondary endpoints include progression-free survival (PFS), duration of response (DOR), and pharmacokinetic parameters such as maximum plasma concentration (Cmax). Inclusion requires documented disease progression following PD-1/PD-L1 therapy and platinum-based chemotherapy, along with confirmed mutation status via tumor tissue or circulating tumor DNA (ctDNA). The trial is estimated to occur between January 2026 and June 2032.

Treatment

Patritumab deruxtecan (MK-1022) is administered as a powder for solution for infusion via intravenous infusion.

MK-1084 is administered in a film-coated tablet pharmaceutical form through oral administration.

Sacituzumab tirumotecan (MK-2870) is provided as a solution for injection for delivery via intravenous infusion.

Cetuximab is administered via intravenous infusion.

Corticosteroids for local oral treatment are utilized as auxiliary therapy via the oral route.

Efficacy

The efficacy of the investigational agent combinations in participants with advanced or metastatic non-small cell lung cancer will be evaluated using several parameters. The primary efficacy endpoint is the objective response rate, which is measured according to RECIST 1.1 and assessed by blinded independent central review.

Secondary efficacy endpoints include:

Duration of response
Progression-free survival

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Has histologically or cytologically confirmed diagnosis of advanced or metastatic non-squamous non-small cell lung cancer (NSCLC)
Has tumor tissue or circulating tumor deoxyribonucleic acid (ctDNA) that demonstrates the presence of Kirsten rat sarcoma viral oncogene (KRAS) mutation of glycine to cysteine at codon 12 (G12C) mutations
Has documented disease progression after receiving 1-2 prior lines of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy and platinum-based chemotherapy
Provides archival tumor tissue sample of a tumor lesion not previously irradiated
Has provided tissue prior to treatment allocation/randomization from a newly obtained biopsy of a tumor lesion not previously irradiated
Participants with human immunodeficiency virus (HIV) infection must have well-controlled HIV on antiretroviral therapy (ART) per protocol

cancel

Exclusion Criteria

Has a diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
Has evidence of any leptomeningeal disease
Has uncontrolled or significant cardiovascular disorder or cerebrovascular disease prior to allocation/randomization
Has one or more of the following ophthalmological conditions: a) Clinically significant corneal disease b) history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis
HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease
Has received previous treatment with an agent targeting KRAS
Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
Has known additional malignancy that is progressing or has required active treatment within the past 3 years
Has history of (noninfectious) pneumonitis/ interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD
Has an active infection requiring systemic therapy
Have not adequately recovered from major surgery or have ongoing surgical complications

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Germany	Recruiting	19 Apr 2026	4
Greece	Recruiting	19 Apr 2026	8
Hungary	Not Yet Recruiting	19 Apr 2026	10
Italy	Recruiting	19 Apr 2026	6
Poland	Not Yet Recruiting	19 Apr 2026	7
Spain	Recruiting	19 Apr 2026	22

Sites & Investigators

Research sites

Bacs-Kiskun Varmegyei Oktatokorhaz Koranyi National Institute For Pulmonology Laiko General Hospital Of Athens Universitaetsklinikum Tuebingen AöR

Investigators

Konstantinos S.Zsuzsanna K.Giuseppe L.Belen R. V.

Investigational Products

Details about the medicinal products being studied in this clinical trial.

Product Name	Role in Trial	Formulation	Administration	Max Daily Dose	Treatment Duration	EU MP Number
CETUXIMAB	Test	PHF00230MIG	INTRAVENOUS INFUSION	—	—	SCP185672
MK-2870	Test	SOLUTION FOR INJECTION	INTRAVENOUS INFUSION	—	—	PRD11447874
MK-1084	Test	TABLET	ORAL	—	—	PRD9352351
MK-1084	Test	FILM-COATED TABLET	ORAL	—	—	PRD12765020
MK-1022	Test	POWDER FOR SOLUTION FOR INFUSION	INTRAVENOUS INFUSION	—	—	PRD11462894
-	Other	PHF00156MIG	ORAL	—	—	A01AC
MK-1084	Test	TABLET	ORAL	—	—	PRD9352352
MK-1084	Test	FILM-COATED TABLET	ORAL	—	—	PRD12769269