A Clinical Study of MK-1084 With Other Treatments for Non-small Cell Lung Cancer (MK-3475-01F)

Official title

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

Overview

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

Detailed description

This is a substudy of the master protocol MK-3475-U01 (KEYMAKER-U01) - NCT04165798.

Per amendment 3, the MK-1084 + Cetuximab arm was discontinued.

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 for prevention of nausea and vomiting, per approved product label. Recommended rescue medications are histamine-1 (H1) receptor antagonist, histamine-2 (H2) receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent infusion, or steroid mouthwash (dexamethasone or equivalent), 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, neurokinin 1 (NK-1) receptor antagonist and corticosteroid.

Primary outcome measures

• Number of Participants Who Experience a Dose Limiting Toxicity (DLT) [Time frame: Up to 42 days]
• Number of Participants Who Experience an Adverse Event (AE) [Time frame: Up to approximately 63 months]
• Number of Participants Who Discontinue Study Treatment Due to an AE [Time frame: Up to approximately 62 months]
• Objective Response Rate (ORR) [Time frame: Up to approximately 63 months]

Secondary outcome measures (5)

• Duration of Response (DOR) [Time frame: Up to approximately 63 months]
• Progression-Free Survival (PFS) [Time frame: Up to approximately 71 months]
• Area Under the Curve From Time 0 to the End of the Dosing Interval (AUC tau) [Time frame: Predose and at designated time points post-dose (up to approximately 63 months)]
• Maximum Plasma Concentration (Cmax) [Time frame: Predose and at designated time points post-dose (up to approximately 63 months)]
• Minimum Observed Concentration (Ctrough) [Time frame: Predose and at designated time points post-dose (up to approximately 63 months)]

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
• Has provided tumor tissue for biomarker analysis from an archival sample or a newly obtained core or excisional 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 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 any history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use or current ILD, or suspected ILD
• Has an active infection requiring systemic therapy
• Has not adequately recovered from major surgery or has ongoing surgical complications

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 4 centers

• Clermont Oncology Center ( Site 0041) — Clermont
• University of Illinois Hospital & Health Sciences System ( Site 0044) — Chicago
• Providence Portland Medical Center ( Site 0043) — Portland
• Providence Oncology and Hematology Care Clinic - Westside ( Site 0059) — Portland

Brazil · 4 centers

• Hospital São Lucas da PUCRS ( Site 0283) — Porto Alegre
• Fundação Pio XII - Hospital de Câncer de Barretos ( Site 0282) — Barretos
• Fundação Faculdade Regional de Medicina de São José do Rio Preto ( Site 0286) — São José do Rio Preto
• Hospital Paulistano ( Site 0280) — São Paulo

Chile · 3 centers

• Centro de Estudios Clínicos SAGA-CECSAGA ( Site 0162) — Santiago
• FALP ( Site 0161) — Santiago
• Bradfordhill ( Site 0160) — Santiago

Greece · 3 centers

• THORACIC GENERAL HOSPITAL OF ATHENS "I SOTIRIA" ( Site 0204) — Athens
• Alexandra General Hospital of Athens-ONCOLOGY DEPT. ( Site 0205) — Athens
• Papageorgiou General Hospital of Thessaloniki ( Site 0206) — N.Efkarpia

Hong Kong · 3 centers

• Queen Mary Hospital ( Site 0230) — Hong Kong
• Hong Kong United Oncology Centre ( Site 0232) — Jordan
• Prince of Wales Hospital ( Site 0231) — Shatin

Israel · 3 centers

• Shaare Zedek Medical Center ( Site 0186) — Jerusalem
• Meir Medical Center ( Site 0181) — Kfar Saba
• Sheba Medical Center ( Site 0180) — Ramat Gan

Spain · 3 centers

• Institut Català d'Oncologia - L'Hospitalet ( Site 0090) — Hospitalet
• Hospital Clinic de Barcelona ( Site 0092) — Barcelona
• Hospital Universitario Virgen Macarena ( Site 0093) — Seville

China · 1 center

• Guangdong Provincial People s Hospital ( Site 0300) — Guangzhou

Germany · 1 center

• UniversitaetsklInikum Tuebingen ( Site 0192) — Tübingen

Italy · 1 center

• IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori" ( Site 0176) — Meldola

South Korea · 1 center

• Severance Hospital, Yonsei University Health System ( Site 0080) — Seoul

Identifiers

NCT: NCT07286149 · 3475-01F · MK-3475-01F · 2024-512248-47-00 · U1111-1304-4707

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗