RecruitingNCT06345729ClinicalTrials.gov record

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)

Non-small Cell Lung Cancer

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THE QUICK READ

What this study involves

The registry says this study is recruiting. Individual locations may have different availability.

Study type: Interventional
Phase: Phase 3
Age range: 18 years - Not specified
Sex eligible: All sexes
Healthy volunteers: Not accepted
Participants: 348 Estimated

These are starting points, not an eligibility decision. The research team must review the full requirements.

About the research

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).

Read the 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.

Who may be able to participate?

The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.

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

Understand screening

Treatment, groups and participation

The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.

Assignment: Random assignment
Masking: Triple masked

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.

Drug: Calderasib · Biological: Pembrolizumab

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.

Other: Placebo · Biological: Pembrolizumab

Calderasib DRUG

Oral tablets

Placebo OTHER

Oral tablets

Pembrolizumab BIOLOGICAL

IV infusion

Prepare your questions

What researchers are measuring

Outcome measures describe what is being studied. They are not proof that a treatment works.

Primary measures

Progression-Free Survival (PFS)

Time frame: Up to approximately 42 months

PFS is defined as the time from randomization until either documented disease progression per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or death due to any cause, whichever occurs first. PFS as determined by blinded independent central review (BICR) will be presented.

Secondary measures

Overall Survival

Time frame: Up to approximately 57 months

OS is defined as the time from randomization to death due to any cause.

Objective Response Rate (ORR)

Time frame: Up to approximately 42 months

ORR is defined as the percentage of participants with Complete Response or Partial Response per RECIST1.1. The percentage of participants who experience CR or PR as assessed by BICR will be presented.

Duration of Response (DOR)

Time frame: Up to approximately 42 months

For participants who demonstrate confirmed CR or PR per RECIST 1.1 as assessed by BICR, duration of response is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.

Number of Participants Who Experience One or More Adverse Event (AEs)

Time frame: Up to approximately 80 months

An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experience an AE will be presented.

Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)

Time frame: Up to approximately 80 months

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score