A Study of Calderasib (MK-1084) Plus Pembrolizumab (MK-3475) in Participants With KRAS G12C Mutant Non-small Cell Lung Cancer (NSCLC) With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥50% (MK-1084-004/KANDLELIT-004)

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 3

Conditions: Non-small Cell Lung Cancer

Treatments: Other: Placebo; Drug: Calderasib; Biological: Pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06345729

KANDLELIT-004 (Other Identifier)

MK-1084-004 (Other Identifier)

1084-004

2023

2023-507776-42-00 (Registry Identifier)

U1111-1296-8093 (Other Identifier)

PHRR241128-007796 (Registry Identifier)

jRCT2031240213 (Registry Identifier)

Details and patient eligibility

About

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 is one primary study hypothesis:

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).

Full description

Per Protocol Amendment 04, overall survival (OS) was moved to be a secondary outcome measure. Additionally, no new participants will be offered Second Course treatment for pembrolizumab.

Enrollment: 348 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 sample (≤5 years) or newly obtained core, incisional, or excisional biopsy or fine needle aspirate (FNA) of a tumor lesion, not previously irradiated to enable central laboratory testing of kirsten rat sarcoma (KRAS) G12C mutation status, programmed cell death ligand 1 (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 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 to non-central nervous system (CNS) disease 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 CNS 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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348 participants in 2 patient groups

Calderasib with Pembrolizumab

Experimental group

Description:

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.

Treatment:

Biological: Pembrolizumab

Drug: Calderasib

Placebo with Pembrolizumab

Active Comparator group

Description:

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.

Treatment:

Biological: Pembrolizumab

Other: Placebo