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Amivantamab plus olomorasib for metastatic KRAS G12C non-small cell lung cancer

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

Phase1; Phase2 Interventional Janssen Research & Development, LLC · NCT07227025

This trial tests whether combining amivantamab and olomorasib can slow tumor growth in people with metastatic non-small cell lung cancer that has a KRAS G12C mutation after platinum chemotherapy and PD‑L1 immunotherapy.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment60 (estimated)
Ages18 Years and up
SexAll
SponsorJanssen Research & Development, LLC Industry-sponsored
Drugs / interventionsamivantamab, chemotherapy, immunotherapy
Locations15 sites (Irvine, California and 14 other locations)
Trial IDNCT07227025 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 trial first determines the recommended Phase 2 combination dose (RP2CD) of amivantamab and olomorasib and then tests that dose for anti-tumor activity in participants with KRAS G12C mutant metastatic NSCLC. Enrollment requires progression on or after platinum-based chemotherapy and PD‑L1‑targeted immunotherapy; Phase 1 allows additional prior therapies while Phase 2 does not. Participants must have at least one measurable lesion per RECIST 1.1 that has not been previously irradiated. Patients receive both study drugs and are monitored with imaging and safety assessments to measure tumor response and tolerability.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed metastatic non-small cell lung cancer harboring a KRAS G12C mutation who have progressed on or after platinum-based chemotherapy and PD‑L1‑targeted immunotherapy and who have at least one measurable, non‑irradiated lesion.

Not a fit: Patients without a KRAS G12C mutation or those who have not received the required prior platinum chemotherapy and PD‑L1 immunotherapy are unlikely to be eligible or benefit from this combination in this trial.

Why it matters

Potential benefit: If successful, the combination could shrink tumors or slow disease progression in patients with KRAS G12C metastatic NSCLC who have progressed after standard chemotherapy and immunotherapy.

How similar studies have performed: KRAS G12C inhibitors have produced tumor responses in prior trials, and combining KRAS‑directed agents with other targeted therapies is an active research approach though not yet definitively proven.

Eligibility criteria

Show full inclusion / exclusion 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

Where this trial is running

Irvine, California and 14 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Carcinoma, Non-Small-Cell Lung
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.