KRASG12C-Mutant NSCLC: AMG510 Phase I Efficacy and Safety

Phase I Trial Results

• October 10, 2019

On September 9, 2019, Amgen announced Phase I trial results of AMG510 (sotorasib), an oral KRAS G12C inhibitor, in previously treated KRASG12C-mutant solid tumors (n=34) with focus on NSCLC subset (n=23).

Molecular Background

KRAS gene family mutations represent the most common genetic alterations in human cancer. KRASG12C mutation incidence:

• Non-small cell lung cancer: ~13%
• Colorectal cancer: 3-5%
• Advanced solid tumors: 1-2%
• United States: ~30,000 annual diagnoses

KRAS mechanism and therapeutic targeting remained unclear until AMG510 development, addressing previously undruggable mutation.

Trial Design

Patient Population: Previously treated KRASG12C-mutant solid tumors (n=34)

Treatment: AMG510 800-960 mg once daily oral monotherapy

Primary Endpoint: Safety

Secondary Endpoints: Objective response rate, response duration

Efficacy Results (n=23 NSCLC-evaluable)

Objective Response Rate (960 mg cohort): 54% (n=13/24)

• Partial response: 54%

Disease Control Rate: 100%

• Partial response: 54%
• Stable disease: 46%

Safety Results (n=34 evaluable)

• Grade 1-2 adverse events: 26.5% (n=9)
• Grade 3 toxicities: 3 patients (anemia, diarrhea)
• Grade 4+ toxicities: None
• Dose-limiting toxicities: Zero
• Treatment discontinuations due to toxicity: Zero

Clinical Conclusions

AMG510 monotherapy meets clinical need for previously treated KRASG12C-mutant NSCLC, with favorable efficacy and safety supporting further clinical development.

Data Source

Amgen WCLC 2019: Novel KRAS G12C Inhibitor Clinical Data

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