Recruiting
Phase 3

MK-1084 & Pembrolizumab

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT06345729

Conditions

Non-small Cell Lung Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Calderasib

Placebo

Pembrolizumab

Study Details

Brief summary:

This is a study evaluating the efficacy and safety of calderasib with pembrolizumab as first-line treatment in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) with identified Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation and programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥50%. There are two primary study hypotheses:

Hypothesis 1: Combination of calderasib and pembrolizumab is superior to placebo plus pembrolizumab with respect to progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).

Hypothesis 2: Combination of calderasib plus pembrolizumab is superior to placebo plus pembrolizumab with respect to overall survival (OS).

Conditions

Non-small Cell Lung Cancer

Study ID

NCT06345729

Start date

May 24, 2024

Status verified date

Sep, 2026

Completion date

Feb 18, 2031

Anticipated

Primary completion date

Feb 19, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

  • Has histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)
  • Has newly diagnosed Stage IIIB/IIIC NSCLC, not eligible for curative resection or curative chemotherapy/radiation as determined by a multidisciplinary tumor board and/or by radiation oncologist, surgeon, and medical oncologist or Stage IV (M1a, M1b, or M1c) by American Joint Committee on Cancer (AJCC) Staging Manual, Version 8
  • Provides an archival tumor tissue sample (≤5 years) or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated to enable central laboratory testing of kirsten rat sarcoma (KRAS) G12C mutation status, PD-L1 status, and biomarker research
  • If have had adverse events (AEs) due to previous anticancer therapies, must have recovered to < Grade 1 or baseline
  • If human immunodeficiency virus (HIV)-infected, must have well controlled HIV on antiretroviral therapy (ART)
  • If Hepatitis B surface antigen (HBsAg) positive, have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load
  • If a participant has a history of Hepatitis C virus (HCV) infection, HCV viral load is undetectable

Exclusion Criteria:

  • Has diagnosis of small cell lung cancer. For mixed tumors, if small cell elements are present, the participant is ineligible
  • Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease
  • Has known history of, or active, neurologic paraneoplastic syndrome
  • Has an active infection requiring systemic therapy, with exceptions
  • Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
  • Has one or more of the following ophthalmological findings/conditions: intraocular pressure >21 mmHg and/or any diagnosis of glaucoma, diagnosis of central serous retinopathy, retinal vein occlusion, or retinal artery occlusion, diagnosis of retinal degenerative disease
  • Has received prior systemic anticancer therapy for their locally advanced or metastatic NSCLC
  • Has received radiation therapy to the lung that is >30 Gray within 6 months of start of study intervention
  • Has received radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not required corticosteroids, and not have had radiation pneumonitis
  • Has known active central nervous system metastases and/or carcinomatous meningitis
  • Known additional malignancy that is progressing or has required active treatment within the past 3 years
  • Has active autoimmune disease that has required systemic treatment in the past 2 years
  • Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
  • Is HIV-infected and has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
  • Has history of allogenic tissue/solid organ transplant
  • Has not fully recovered from any effects of major surgical procedure

Study Design

Enrollment

600 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Calderasib with Pembrolizumab

Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles and calderasib by oral tablets until discontinuation criterion is met.

active comparator: Placebo with Pembrolizumab

Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles and placebo by oral tablets once daily until discontinuation criterion is met.

Interventions

Calderasib

Oral tablets

Placebo

Oral tablets

Pembrolizumab

IV infusion

Primary outcome measure

  • Progression-Free Survival (PFS) [ Time Frame: Up to approximately 42 months ]
  • Overall Survival (OS) [ Time Frame: Up to approximately 56 months ]

Central Contacts and Locations

Central contacts

Toll Free Number

1-888-577-8839Trialsites@msd.com

Locations

CBCC Global Research, Inc. ( Site 0123)

Recruiting

Bakersfield, California, United States, 93309

Contacts

Study Coordinator

661-322-2206

Beverly Hills Cancer Center ( Site 0116)

Recruiting

Beverly Hills, California, United States, 90211

Contacts

Study Coordinator

310-432-8955

Stamford Hospital ( Site 0136)

Recruiting

Stamford, Connecticut, United States, 06902

Contacts

Study Coordinator

877-233-9355

Orchard Healthcare Research Inc. ( Site 0115)

Recruiting

Skokie, Illinois, United States, 60077

Contacts

Study Coordinator

224-534-7580

Truman Medical Center ( Site 0126)

Recruiting

Kansas City, Missouri, United States, 64108

Contacts

Study Coordinator

816-404-4093

Cox Medical Center North ( Site 0133)

Recruiting

Springfield, Missouri, United States, 65807

Contacts

Study Coordinator

417-875-3000

St. Vincent Frontier Cancer Center-Research ( Site 0105)

Recruiting

Billings, Montana, United States, 59102

Contacts

Study Coordinator

402-238-6685

Atlantic Health System Morristown Medical Center ( Site 0121)

Recruiting

Morristown, New Jersey, United States, 07960

Contacts

Study Coordinator

973-275-7788

New York Oncology Hematology, P.C. ( Site 0132)

Recruiting

Albany, New York, United States, 12206

Contacts

Study Coordinator

518-489-3612

University of Cincinnati Medical Center-University of Cincinnati Cancer Center ( Site 0103)

Recruiting

Cincinnati, Ohio, United States, 45219

Contacts

Study Coordinator

513-556-6000

Lancaster General Hospital - Ann B Barshinger Cancer Institute ( Site 0134)

Recruiting

Lancaster, Pennsylvania, United States, 17601

Contacts

Study Coordinator

717-544-9400

Oncology Consultants P.A. ( Site 0113)

Recruiting

Houston, Texas, United States, 77030

Contacts

Study Coordinator

713-600-0900

Circuit Clinical/SSM Health Dean Medical Group ( Site 0129)

Recruiting

Madison, Wisconsin, United States, 53715

Contacts

Study Coordinator

608-410-2767

CancerCare Manitoba ( Site 0210)

Recruiting

Winnipeg, Manitoba, Canada, R3E 0V9

Contacts

Study Coordinator

204-787-4156

QEII Health Sciences Centre - Victoria General Site-Dept. of Medical Oncology ( Site 0208)

Recruiting

Halifax, Nova Scotia, Canada, B3H 2Y9

Contacts

Study Coordinator

9024737964

Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0205)

Recruiting

Hamilton, Ontario, Canada, L8V 5C2

Contacts

Study Coordinator

9053879495

Sunnybrook Research Institute ( Site 0206)

Recruiting

Toronto, Ontario, Canada, M4N 3M5

Contacts

Study Coordinator

4164805000x687435

St. Marys Hospital Center ( Site 0204)

Recruiting

Montreal, Quebec, Canada, H3T 1M5

Contacts

Study Coordinator

5143453511

Centre integre universitaire de sante et de services sociaux de la Mauricie-et-du-centre-du-quebec ( Site 0207)

Recruiting

Trois-Rivières, Quebec, Canada, G8Z 3R9

Contacts

Study Coordinator

8196973333x63238

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Sep 8, 2026

Last verified

Sep, 2026

Keywords

  • Programmed Cell Death-1 (PD1, PD-1)
  • Programmed Cell Death 1 Ligand 1(PDL1, PD-L1)
  • Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
  • Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-09-08.