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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2, Multicenter, Open-label Study of Sotorasib (AMG 510) in Subjects With Stage IV NSCLC Whose Tumors Harbor a KRAS G12C Mutation in Need of First-line Treatment (CodeBreaK 201)

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Sotorasib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sotorasib: 960 mg Daily<br>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. | Drug: Sotorasib<br>* Oral tablet<br>* Other names: LUMAKRAS;|
| Experimental: Sotorasib: 240 mg Daily<br>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. | Drug: Sotorasib<br>* Oral tablet<br>* Other names: LUMAKRAS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (OR) | OR is defined as the total of Complete Response (CR) and Partial Response (PR). | Up to 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate |  | Up to 6 years | 
| Duration of Reponse (DOR) |  | Up to 6 years | 
| Time to Response (TTR) |  | Up to 6 years | 
| Progression-free Survival (PFS) |  | Up to 6 years | 
| Overall Survival (OS) |  | Up to 6 years | 
| Number of Participants with a Treatment-emergent Adverse Event (TEAE) |  | Day 1 up to Month 13 | 
| Number of Participants with a Treatment-related Adverse Event |  | Day 1 up to Month 13 | 
| Number of Participants with a Clinically Significant Change from Baseline in Vital Signs |  | Baseline (Screening; up to 28 days pre-dose) up to Month 13 | 
| Number of Participants with a Clinically Significant Change from Baseline in Electrocardiograms (ECGs) |  | Baseline (Screening; up to 28 days pre-dose) up to Month 13 | 
| Number of Participants with a Clinically Significant Change from Baseline in Clinical Laboratory Tests |  | Baseline (Screening; up to 28 days pre-dose) up to Month 13 | 
| Maximum Plasma Concentration (Cmax) of Sotorasib |  | Day 1 up to Month 3 | 
| Time to Reach Maximum Plasma Concentration (tmax) of Sotorasib |  | Day 1 up to Month 3 | 
| Area Under the Plasma Concentration-time Curve (AUC) of Sotorasib |  | Day 1 up to Month 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-small cell lung cancer, KRAS p.G12C, Sotorasib, AMG 510