KEYMAKER-U01 Substudy 01F: A Phase 1b/2 Umbrella Study With Rolling Arms of Investigational Agents for Previously Treated Participants With Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With KRAS G12C Mutations

Plain English Summary

A Clinical Study of MK-1084 With Other Treatments for Non-small Cell Lung Cancer (MK-3475-01F) is a Phase 2 clinical trial sponsored by Merck Sharp & Dohme LLC studying Lung Neoplasm Malignant. This study tests a new drug called MK-1084, alone or with other treatments, for advanced lung cancer. It is for patients with a specific type of non-small cell lung cancer (NSCLC) that has spread and has a KRAS G12C mutation. Participants will receive study treatments and be monitored for side effects and how well the cancer responds. Standard treatments for advanced NSCLC include chemotherapy, immunotherapy, and targeted therapies. The trial aims to enroll 190 participants.

Official Summary

Researchers want to learn if MK-1084, the study medicine, can treat advanced or metastatic non-squamous NSCLC. MK-1084 is a targeted therapy, which is a treatment that works to control how specific types of cancer cells grow and spread. The goals of this study are to learn: * About the safety of MK-1084 and if people tolerate it when taken with other treatments * How many people have the cancer respond (get smaller or go away) to the treatments

Who Can Participate

Here is what you need to know about eligibility for this trial. You may be eligible if you have advanced or metastatic non-squamous NSCLC with a KRAS G12C mutation. You must have had at least one to two prior treatments, including immunotherapy and chemotherapy. You cannot join if you have small cell lung cancer, active brain metastases, or have previously been treated with a KRAS-targeting drug. Age is not specified, but general health and absence of severe lung or heart conditions are required. This trial is studying Lung Neoplasm Malignant, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure how safe the treatments are, how many people experience side effects, and how many patients' tumors shrink or disappear. The specific primary outcome measures are: Number of Participants Who Experience a Dose Limiting Toxicity (DLT) (Up to 42 days); Number of Participants Who Experience an Adverse Event (AE) (Up to approximately 65 months); Number of Participants Who Discontinue Study Treatment Due to an AE (Up to approximately 64 months); Objective Response Rate (ORR) (Up to approximately 65 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for new treatments in lung cancer patients with specific KRAS G12C mutations who have not responded to standard therapies. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Lung Neoplasm Malignant, where improved treatment options are needed.

Investor Insight

This study targets a growing area of precision medicine in oncology, with potential for significant market impact if successful in a difficult-to-treat patient population. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if your lung cancer has the KRAS G12C mutation and if this study is a good option for you. Participation involves receiving study drugs, regular clinic visits, and tests to monitor your health and cancer. Be prepared for potential side effects and discuss any concerns with your healthcare team. This trial is currently recruiting participants. The trial is being conducted at 4 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 190 participants

Interventions

• DRUG: MK-1084 — Oral administration
• BIOLOGICAL: Patritumab deruxtecan — IV infusion
• BIOLOGICAL: Sacituzumab tirumotecan — IV Infusion
• BIOLOGICAL: Cetuximab — IV Infusion
• DRUG: Rescue Medications — Participants receive rescue medication at the investigator's discretion, per approved product label. Recommended rescue medications are histamine -1 (H1) receptor agonist, histamine-2 (H2) receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent infusion, or steroid mouthwash (dexamethasone or equivalent) for prevention of chemotherapy induced nausea and vomiting.

Primary Outcomes

• Number of Participants Who Experience a Dose Limiting Toxicity (DLT) (Up to 42 days)
• Number of Participants Who Experience an Adverse Event (AE) (Up to approximately 65 months)
• Number of Participants Who Discontinue Study Treatment Due to an AE (Up to approximately 64 months)
• Objective Response Rate (ORR) (Up to approximately 65 months)

Secondary Outcomes

• Duration of Response (DOR) (Up to approximately 65 months)
• Progression-Free Survival (PFS) (Up to approximately 124 months)
• Area Under the Curve From Time 0 to the End of the Dosing Interval (AUC tau) (Predose and at designated time points post-dose (up to approximately 65 months))
• Maximum Plasma Concentration (Cmax) (Predose and at designated time points post-dose (up to approximately 65 months))
• Minimum Observed Concentration (Ctrough) (Predose and at designated time points post-dose (up to approximately 65 months))

Full Eligibility Criteria

Inclusion Criteria:

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

* 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

Exclusion Criteria:

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

* 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 Locations

• Clermont Oncology Center ( Site 0041), Clermont, Florida, United States
• Shaare Zedek Medical Center ( Site 0186), Jerusalem, Israel
• Sheba Medical Center ( Site 0180), Ramat Gan, Israel
• Severance Hospital, Yonsei University Health System ( Site 0080), Seoul, South Korea

Frequently Asked Questions

Related Conditions

• Non-small Cell Lung Cancer
• Lung Neoplasm Malignant
• Metastatic Lung Cancer
• KRAS G12C Mutation
• Targeted Cancer Therapy
• Immunotherapy
• Chemotherapy
• Advanced Lung Cancer
• Thoracic Oncology
• Precision Medicine in Oncology

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