A Study of Sotorasib (AMG 510) in Participants With Stage IV NSCLC Whose Tumors Harbor a KRAS p.G12C Mutation in Need of First-line Treatment (CodeBreaK201)

Amgen

Status and phase: Active, not recruiting; Phase 2

Conditions: Non-small Cell Lung Cancer

Treatments: Drug: Sotorasib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04933695

20190288

2021-002638-18 (EudraCT Number)

Details and patient eligibility

About

The main objective of this study is to evaluate the tumor objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in participants who receive sotorasib at either 960 mg daily or 240 mg daily whose tumors are programmed death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) < 1% and/or harbor a serine/threonine kinase 11 (STK11) co-mutation, in a subgroup of participants with PD-L1 < 1% and in a subgroup of participants with STK11 co-mutation.

Enrollment: 42 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult (= or > 18 years old) with NSCLC
• Untreated Stage IV metastatic disease. Participants who received adjuvant or neoadjuvant anti-tumor therapy are eligible if the adjuvant/neoadjuvant therapy was completed greater than 12 months prior to the development of metastatic stage IV disease
• Pathologically documented metastatic NSCLC with KRAS G12C mutation (local confirmation)
• Programmed death-ligand 1 (PD-L1) TPS Score < 1% and/or serine/threonine kinase 11 (STK11) co-mutation (local confirmation)
• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
• No active brain metastases
• Measurable disease per investigator interpretation using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

Exclusion criteria

• Mixed small-cell lung cancer and NSCLC histology
• Myocardial Infarction within 6 months of study Day 1
• Use of proton-pump inhibitors (PPIs), histamine (H2) receptor antagonists (H2RA), strong inducers of cytochrome P450 (CYP) 3A4 (CYP3A4) or known CYP3A4 sensitive substrates or P-gp substrates
• Therapeutic or palliative radiation therapy within 2 weeks of study day 1
• Unable to take oral medication
• Unable to receive both iodinated contrast for computed tomography (CT) scans and gadolinium contrast for magnetic resonance imagine (MRI) scans

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

42 participants in 2 patient groups

Sotorasib: 960 mg Daily

Experimental group

Description:

Participants with metastatic non-small cell lung cancer (NSCLC) with Kirsten rat sarcoma (KRAS) p.G12C mutation whose tumors express \< 1% programmed death-ligand 1 (PD-L1) and/or serine/threonine kinase 11 (STK11) mutation in need of first line treatment will be administered sotorasib 960 mg daily. Participants will be stratified by known presence of STK11 mutation.

Treatment:

Drug: Sotorasib

Sotorasib: 240 mg Daily

Experimental group

Description:

Participants with metastatic non-small cell lung cancer (NSCLC) with Kirsten rat sarcoma (KRAS) p.G12C mutation whose tumors express \< 1% programmed death-ligand 1 (PD-L1) and/or serine/threonine kinase 11 (STK11) mutation in need of first line treatment will be administered sotorasib 240 mg daily. Participants will be stratified by known presence of STK11 mutation.

Treatment:

Drug: Sotorasib