FDA Approval Summary: Sotorasib for KRAS G12C-Mutated Metastatic NSCLC

Overview

Journal Clin Cancer Res

Specialty Oncology

Date 2021 Dec 14

PMID 34903582

Citations 99

Authors

Erica C Nakajima

Nicole Drezner

Xiaoxue Li

Pallavi S Mishra-Kalyani

Yajun Liu

Hong Zhao

Youwei Bi

Jiang Liu

Atiqur Rahman

Emily Wearne

Idara Ojofeitimi

Lauren Tesh Hotaki

Dianne Spillman

Richard Pazdur

Julia A Beaver

Harpreet Singh

Affiliations

Soon will be listed here.

Abstract

On May 28, 2021, the FDA granted accelerated approval to sotorasib (Lumakras, Amgen) for the treatment of adults with advanced non-small cell lung cancer (NSCLC) with a Kirsten rat sarcoma proto-oncogene (KRAS) G12C mutation who have received at least one prior systemic therapy. The approval was based on CodeBreaK 100 (Study 20170543), a dose-escalation and dose-expansion trial in patients with an advanced, KRAS G12C-mutated, solid tumor. The overall response rate (ORR) observed in patients with KRAS G12C-mutated NSCLC treated with sotorasib (n = 124) was 36% [95% confidence interval (CI), 28-45]. The median duration of response was 10.0 months (95% CI, 6.9-not estimable). The most common adverse reactions (≥20%) were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough. This is the first approval of a targeted therapy for KRAS G12C-mutated NSCLC. Because of pharmacokinetic data and ORRs of patient cohorts who took sotorasib at lower doses in the dose-escalation portion of CodeBreaK 100, a dose comparison study is being conducted as a post-marketing requirement.

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