A Study of Amivantamab and Olomorasib Combination Therapy in Participants With Metastatic Non-Small Cell Lung Cancer

NCT07227025 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 61186372PANSC2004
• Study Type: interventional
• Target: 60
• Locations: 5 countries
• Sites: 15

Brief 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 \[C\]).

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (3)

• 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).

  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.

  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).

  Up to approximately 3 years 2 months

Secondary Outcomes (6)

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

  Up to approximately 3 years 2 months

• Number of Participants with Abnormalities in Clinical Laboratory Parameters

  Up to approximately 3 years 2 months

• Phase 2: Duration of Response (DoR)

  Up to approximately 3 years 2 months

• Phase 2: Disease Control Rate (DCR)

  Up to approximately 3 years 2 months

• Phase 2: Progression-Free Survival (PFS)

  Up to approximately 3 years 2 months

Study Arms (2)

Phase 1: Combination Dose Selection

EXPERIMENTAL

Participants will receive amivantamab along with olomorasib to determine the RP2CD of the combination therapy until disease progression, significant toxicity, or until another criterion for discontinuation of study treatment is met. Eligible participants may have the option to transfer to a long-term extension (LTE) phase for continued access to study treatments.

Drug: Amivantamab; Drug: Olomorasib

Phase 2: Expansion

EXPERIMENTAL

Participants will receive amivantamab and olomorasib combination therapy at the RP2CD determined in Phase 1 until disease progression, significant toxicity, or until another criterion for discontinuation of study treatment is met. Eligible participants may have the option to transfer to LTE phase for continued access to study treatments.

Drug: Amivantamab; Drug: Olomorasib

Interventions

Amivantamab DRUG

Amivantamab will be administered.

Also known as: JNJ-61186372, RYBREVANT

Phase 1: Combination Dose Selection; Phase 2: Expansion

Olomorasib DRUG

Olomorasib will be administered.

Also known as: LY3537982

Phase 1: Combination Dose Selection; Phase 2: Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (15)

University of California Irvine

Irvine, California, 92697, United States

SUSPENDED

New York University Langone Medical Center

New York, New York, 10016, United States

RECRUITING

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

Philadelphia, Pennsylvania, 19104, United States

SUSPENDED

Oncology Consultants Cancer Center

Houston, Texas, 77030, United States

SUSPENDED

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

NorthWest Medical Specialties, PLLC

Puyallup, Washington, 98373, United States

SUSPENDED

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

The First Affiliated Hospital Sun Yat sen University

Guangzhou, 510060, China

RECRUITING

Shanghai East Hospital

Shanghai, 310000, China

RECRUITING

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

Ankara Universitesi Hastaneleri Tibbi Farmakoloji Anabilim Dali Faz 1 Klinik Arastirma Merkezi

Ankara, 06620, Turkey (Türkiye)

RECRUITING

Ankara Bilkent Sehir Hastanesi

Çankaya, 06800, Turkey (Türkiye)

RECRUITING

Koc Universitesi Hastanesi Faz 1 Klinik Arastirma Merkezi

Istanbul, 34010, Turkey (Türkiye)

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

amivantamab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Central Study Contacts

Study Contact

CONTACT

844-434-4210; Participate-In-This-Study1@its.jnj.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2025
• First Posted: November 12, 2025
• Study Start: March 3, 2026
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): April 30, 2029
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

CN (2); CA (1); US (6); KR (3); TU (3)