Cancerify Logo
Log inSign up
Back to clinical trials
RecruitingInterventionalPhase 1/Phase 2

A Phase 1/2 Study Evaluating the Safety and Efficacy of Amivantamab and Olomorasib Combination Therapy in Metastatic Non-small Cell Lung Cancer

NCT ID: NCT07227025Sponsor: Janssen Research & Development, LLCLast updated: 2026-06-05

Summary

The main purpose of this study is to find out the most suitable dose (recommended phase 2 combination dose \[RP2CD\]) of amivantamab and olomorasib combination therapy and to assess how well the combination slows down or prevents the growth of tumors in participants with KRAS G12C mutant metastatic non-small cell lung cancer (NSCLC: the most common type of lung cancer; metastatic: has spread to other parts of the body; KRAS G12C mutant: mutation \[change\] in the kirsten rat sarcoma viral oncogene homolog \[KRAS\] gene in tumor cells in which glycine \[G\] at position 12 is replaced with cystine \[C\]).

Arms & interventions

  • DrugAmivantamab

    Amivantamab will be administered.

  • DrugOlomorasib

    Olomorasib will be administered.

Outcome measures

Primary

  • Phase 1: Number of Participants with Adverse Events (AEs) by Severity

    An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An assessment of severity grade will be made by the investigator according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 defined as follows: Grade 1 (mild; asymptomatic or mild symptoms; intervention not indicated); Grade 2 (moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living \[ADL\]); Grade 3 (severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4 (life-threatening consequences; urgent intervention indicated); Grade 5 (Death related to adverse event).

    Time frame: Up to approximately 3 years 2 months

  • Phase 1: Number of Participants with Dose-Limiting Toxicities (DLTs)

    DLT is defined as drug related adverse events and includes unacceptable non-hematologic toxicity, hematologic toxicity, pulmonary toxicity, or elevations in hepatic enzymes suggestive of drug-induced liver injury of Grade 3 or higher. Toxicities will be graded for severity according to the NCI-CTCAE, version 5.0.

    Time frame: Up to approximately 3 years 2 months

  • Phase 2: Confirmed Objective Response Rate (ORR)

    ORR is defined as the percentage of participants who achieve either a confirmed partial response (PR) or complete response (CR), using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 by investigator review. Confirmatory analysis may be performed using Blinded Independent Central Review (BICR).

    Time frame: Up to approximately 3 years 2 months

Secondary

  • Number of Participants with Adverse Events (AEs) by Severity

    Time frame: Up to approximately 3 years 2 months

  • Number of Participants with Abnormalities in Clinical Laboratory Parameters

    Time frame: Up to approximately 3 years 2 months

  • Phase 2: Duration of Response (DoR)

    Time frame: Up to approximately 3 years 2 months

  • Phase 2: Disease Control Rate (DCR)

    Time frame: Up to approximately 3 years 2 months

  • Phase 2: Progression-Free Survival (PFS)

    Time frame: Up to approximately 3 years 2 months

  • Phase 2: Overall Survival (OS)

    Time frame: Up to approximately 3 years 2 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion criteria: * Participant must have histologically or cytologically confirmed metastatic NSCLC characterized by a KRAS G12C mutation at the time of enrollment. For Phase 1: Participant must have progressed on or after, or have intolerance to, platinum-based chemotherapy and Programmed Death-Ligand 1 (PD-L1)-targeted immunotherapy given in combination or sequentially. Receipt of additional lines of prior therapy is permitted. Progression must have occurred on or after the most recent line of systemic anticancer therapy. For Phase 2: Participant must have progressed on or after platinum-based chemotherapy and PD-L1-targeted immunotherapy given in combination or sequentially. Progression must have occurred on or after the most recent line of systemic anticancer therapy. Receipt of additional lines of prior therapy is not permitted * Participant must have at least 1 measurable lesion, according to RECIST version.1.1, that has not been previously irradiated * May have brain metastases only if previously definitively, locally treated, and participant is clinically stable and asymptomatic for greater than (\>) 2 weeks and is off or receiving low-dose corticosteroid treatment for at least 2 weeks prior to start of study treatment * Can have a prior or concurrent second malignancy (other than the disease under study) with natural history or treatment course that is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s) * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Exclusion criteria: * Participant has history of uncontrolled illness * Suspected or known allergies, hypersensitivity, or intolerance to amivantamab excipients or olomorasib excipients * Medical history of (non-infectious) interstitial lung disease (ILD)/pneumonitis, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening * Presence of primary driver mutations (epidermal growth factor receptor \[EGFR\], anaplastic lymphoma kinase \[ALK\], mesenchymal-epithelial transition \[MET\], human epidermal growth factor receptor 2 \[HER2\], ROS1, neurotrophic tyrosine receptor kinase \[NTRK\], B-Raf proto-oncogene \[BRAF\], rearranged during Transfection \[RET\], neuroblastoma RAS viral oncogene homolog \[NRAS\], and other KRAS mutations besides G12C) as determined by local genomic testing * Prior treatment with any KRAS inhibitor

Study locations (6)

University of California Irvine

Irvine, California, 92697

Suspended

New York University Langone Medical Center

New York, New York, 10016

Recruiting

University of Pennsylvania Division of Hematology Oncology Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104

Suspended

Oncology Consultants Cancer Center

Houston, Texas, 77030

Suspended

Virginia Cancer Specialists

Fairfax, Virginia, 22031

Recruiting

NorthWest Medical Specialties, PLLC

Puyallup, Washington, 98373

Suspended