FDA Approves Sotorasib (Lumakras) in Combination with Panitumumab for Chemotherapy-Refractory KRAS G

On January 17, 2025, Amgen announced that the U.S. Food and Drug Administration (FDA) has approved the combination of Sotorasib (Lumakras) and Panitumumab (Vectibix) for the treatment of adult patients with KRAS G12C-mutated metastatic colorectal cancer (mCRC), as detected by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. This approval is based on the pivotal Phase 3 CodeBreaK 300 study, which demonstrated that the Sotorasib plus Vectibix combination is the first and only targeted therapy combination for chemotherapy-refractory KRAS G12C-mutated metastatic colorectal cancer, showing superior progression-free survival (PFS) compared to the studied standard of care (SOC).

Dr. Jay Bradner, Executive Vice President of Research and Development at Amgen, stated: "Colorectal cancer is the third leading cause of cancer-related death in the United States, and fewer than one in five patients diagnosed with metastatic disease survive beyond five years after diagnosis. Lumakras in combination with Vectibix offers a biomarker-directed targeted therapy combination that more effectively delays disease progression compared to the studied standard of care. This new option confirms the value of our combination approach in improving outcomes for patients with advanced KRAS G12C-mutated metastatic colorectal cancer."

"Ongoing innovation and precision medicine are urgently needed to help those affected by metastatic colorectal cancer," said Michael Sapienza, CEO of the Colorectal Cancer Alliance. "This new combination therapy represents a significant breakthrough for patients with KRAS G12C-mutated metastatic colorectal cancer, providing a new and beneficial treatment option for those facing this devastating and highly challenging disease."

About Metastatic Colorectal Cancer (mCRC) and the KRAS G12C Mutation

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide and the third most commonly diagnosed cancer globally. Patients with previously treated metastatic colorectal cancer require more effective treatment options. For patients in the third-line setting, standard therapies result in a median overall survival (OS) of less than one year, with response rates below 10%. KRAS mutations are among the most common genetic alterations in colorectal cancer, with KRAS G12C mutations identified in approximately 3%–5% of colorectal cancer cases as determined by FDA-approved biomarker tests.

About Sotorasib (Lumakras)

Sotorasib (Lumakras) received accelerated approval from the U.S. Food and Drug Administration (FDA) on May 28, 2021. On December 26, 2023, the FDA completed its review of Amgen's supplemental new drug application (sNDA) seeking full approval for Sotorasib (Lumakras), resulting in a complete response letter.

Additionally, the FDA determined that the postmarketing requirement (PMR) mandated at the time of Sotorasib's accelerated approval—to evaluate the safety and efficacy of the 960 mg daily dose compared with a lower daily dose—has been satisfied. The company stated that under accelerated approval, the 960 mg once-daily dose of Sotorasib (Lumakras) for patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC) remains unchanged.