Recruiting
Phase 1
Phase 2

Amivantamab & Olomorasib

Sponsor:

Janssen Research & Development, LLC

Code:

NCT07227025

Conditions

Carcinoma, Non-Small-Cell Lung

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Amivantamab

Olomorasib

Study Details

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 ID

NCT07227025

Start date

Mar 3, 2026

Status verified date

Aug, 2026

Completion date

Apr 30, 2029

Anticipated

Primary completion date

Nov 30, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

60 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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.

experimental: 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.

Interventions

Amivantamab

Amivantamab will be administered.

Olomorasib

Olomorasib will be administered.

Primary outcome measure

  • Phase 1: Number of Participants with Adverse Events (AEs) by Severity [ Time Frame: Up to approximately 3 years 2 months ]
  • Phase 1: Number of Participants with Dose-Limiting Toxicities (DLTs) [ Time Frame: Up to approximately 3 years 2 months ]
  • Phase 2: Confirmed Objective Response Rate (ORR) [ Time Frame: Up to approximately 3 years 2 months ]

Central Contacts and Locations

Central contacts

Study Contact

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

Locations

New York University Langone Medical Center

Recruiting

New York, New York, United States, 10016

Virginia Cancer Specialists

Recruiting

Fairfax, Virginia, United States, 22031

Princess Margaret Hospital

Recruiting

Toronto, Ontario, Canada, M5G 2M9

More Information

Sponsor

Janssen Research & Development, LLC

Last update posted

Aug 28, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Janssen Research & Development, LLC on 2026-08-28.