Sotorasib Earns Accelerated Approval for KRAS G12C+ NSCLC

Based on data from the phase 1/2 CodeBreaK 100 trial, the FDA approved the KRAS G12C inhibitor sotorasib.

The FDA granted accelerated approval to sotorasib (Lumakras) as the first targeted therapy for patients with non–small cell lung cancer (NSCLC) whose tumors express a KRAS G12C mutation and who have received at least 1 prior therapy for their disease, according to the company responsible for developing the agent, Amgen.1,2

The decision was based on data from the phase 1/2 CodeBreaK 100 clinical trial (NCT03600883) that demonstrated the agent’s ability to induce deep and durable responses in the indicated patient population.

“Sotorasib represents a major advancement in oncology and changes the treatment paradigm for patients with KRAS G12C–mutated non–small cell lung cancer,” Bob T. Li, MD, PhD, MPH, principal investigator at Memorial Sloan Kettering Cancer Center, said in a press release. “Patients with non–small cell lung cancer who have progressed beyond first-line treatment face a poor prognosis and have limited treatment options available to them. Sotorasib delivers a new option for these patients, and it is the first KRAS-targeted therapy to be approved after nearly four decades of research.”

In 124 evaluable patients with locally advanced or metastatic disease progressing after an immune checkpoint inhibitor and/or platinum-based chemotherapy, the objective response rate with sotorasib was 36% (95% CI, 28%-45%) with 56% of patients maintaining a response longer than 6 months. The disease control rate—comprised of patients achieving complete and partial responses or stable disease–was 81% (95% CI, 73%-87%).

The most common adverse effects of sotorasib include diarrhea, musculoskeletal pain, nausea, fatigue, liver damage and cough.

“The FDA approval of Lumakras is a breakthrough moment for patients with KRAS G12C–mutated non–small cell lung cancer because there is now a targeted therapy for this common, but previously elusive, mutation,” David M. Reese, MD, executive vice president of Research and Development at Amgen, said in a press release. “KRAS has challenged cancer researchers for more than 40 years with many deeming it as 'undruggable.' The Lumakras development program was a race against cancer for Amgen's scientists and clinical trial investigators who together have now successfully delivered this new medicine to patients in less than three years—from first patient dosed to US regulatory approval.”

In addition to this approval, the FDA granted regulatory approval to the therascreen KRAS RGQ PCR Kit and the Guardant360 CDx test as companion diagnostics to identify patients with NSCLC who are eligible to receive sotorasib.3,4

The global, randomized, active-controlled phase 3 CodeBreaK 200 study (NCT04303780) is currently ongoing in patients with previously treated KRAS G12C–mutant NSCLC. The trial will investigate sotorasib compared with docetaxel as treatment for their disease.


1. FDA Approves First Targeted Therapy for Lung Cancer Mutation Previously Considered Resistant to Drug Therapy. News release. FDA. May 28, 2021. Accessed May 28, 2021.

2. FDA Approves Lumakras (Sotorasib), The First And Only Targeted Treatment For Patients With KRAS G12C-Mutated Locally Advanced Or Metastatic Non-Small Cell Lung Cancer. News release. Amgen. May 28, 2021. Accessed May 28, 2021.

3. QIAGEN Launches First FDA-approved Tissue Companion Diagnostic to Identify the KRAS G12C Mutation in NSCLC Tumours and Expand Precision Medicine Options in Lung Cancer. News release. QIAGEN N.V. May 28, 2021. Accessed June 2, 2021.

4. Guardant360 CDx Receives FDA Approval as First and Only Liquid Biopsy Companion Diagnostic for Amgen’s LUMAKRAS™ (sotorasib) KRASG12C Inhibitor for Use in Advanced Non-Small Cell Lung Cancer. News release. Guardant Health, Inc. May 28, 2021. Accessed June 2, 2021.