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NCT07227025PHASE1, PHASE2Recruiting

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

Janssen Research & Development, LLC

Start Date

3/3/2026

Completion Date

4/30/2029

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 \[C\]).

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

Amivantamab

DRUG

Olomorasib

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Conditions

Carcinoma, Non-Small-Cell Lung

Locations

New York University Langone Medical Center

New York, New York 10016

United States

Oncology Consultants Cancer Center

Houston, Texas 77030

United States

Virginia Cancer Specialists

Fairfax, Virginia 22031

United States

Princess Margaret Hospital

Toronto, Ontario M5G 2M9

Canada

The First Affiliated Hospital Sun Yat sen University

Guangzhou, 510060

China

Harbin medical university cancer hospital

Harbin, 150000

China

Shanghai East Hospital

Shanghai, 310000

China

Severance Hospital Yonsei University Health System

Seoul, 03722

South Korea

Asan Medical Center

Seoul, 05505

South Korea

Samsung Medical Center

Seoul, 06351

South Korea

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

Ankara, 06620

Turkey (Türkiye)

Ankara Bilkent Sehir Hastanesi

Çankaya, 06800

Turkey (Türkiye)

Koc Universitesi Hastanesi Faz 1 Klinik Arastirma Merkezi

Istanbul, 34010

Turkey (Türkiye)