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

Official title

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

Overview

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 \[C\]).

Interventions

• Drug Amivantamab
  Amivantamab will be administered.
• Drug Olomorasib
  Olomorasib will be administered.

Primary outcome measures

• 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]

Secondary outcome measures (6)

• Number of Participants with Adverse Events (AEs) by Severity [Time frame: Up to approximately 3 years 2 months]
• Number of Participants with Abnormalities in Clinical Laboratory Parameters [Time frame: Up to approximately 3 years 2 months]
• Phase 2: Duration of Response (DoR) [Time frame: Up to approximately 3 years 2 months]
• Phase 2: Disease Control Rate (DCR) [Time frame: Up to approximately 3 years 2 months]
• Phase 2: Progression-Free Survival (PFS) [Time frame: Up to approximately 3 years 2 months]
• Phase 2: Overall Survival (OS) [Time frame: Up to approximately 3 years 2 months]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 3 centers

• New York University Langone Medical Center — New York
• Oncology Consultants Cancer Center — Houston
• Virginia Cancer Specialists — Fairfax

China · 3 centers

• The First Affiliated Hospital Sun Yat sen University — Guangzhou
• Harbin medical university cancer hospital — Harbin
• Shanghai East Hospital — Shanghai

South Korea · 3 centers

• Severance Hospital Yonsei University Health System — Seoul
• Asan Medical Center — Seoul
• Samsung Medical Center — Seoul

Turkey (Türkiye) · 3 centers

• Ankara Universitesi Hastaneleri Tibbi Farmakoloji Anabilim Dali Faz 1 Klinik Arastirma Mer — Ankara
• Ankara Bilkent Sehir Hastanesi — Çankaya
• Koc Universitesi Hastanesi Faz 1 Klinik Arastirma Merkezi — Istanbul

Canada · 1 center

• Princess Margaret Hospital — Toronto

Identifiers

NCT: NCT07227025 · 61186372PANSC2004 · 61186372PANSC2004

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗