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

NCT ID: NCT07227025

Last Updated: 2025-11-12

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-22
• Study Completion Date: 2028-11-30

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1: Combination Dose Selection

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.

Group Type: EXPERIMENTAL

Amivantamab

Intervention Type: DRUG

Amivantamab will be administered.

Olomorasib

Intervention Type: DRUG

Olomorasib will be administered.

Phase 2: Expansion

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.

Group Type: EXPERIMENTAL

Amivantamab

Intervention Type: DRUG

Amivantamab will be administered.

Olomorasib

Intervention Type: DRUG

Olomorasib will be administered.

Interventions

Amivantamab

Amivantamab will be administered.

Intervention Type: DRUG

Olomorasib

Olomorasib will be administered.

Intervention Type: DRUG

Other Intervention Names

JNJ-61186372; RYBREVANT; LY3537982

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Central Contacts

Study Contact

Role: CONTACT

Phone: 844-434-4210

Email: Participate-In-This-Study1@its.jnj.com

Other Identifiers

61186372PANSC2004

Identifier Type: OTHER

Identifier Source: secondary_id

61186372PANSC2004

Identifier Type: -

Identifier Source: org_study_id