FDA Approves Amgen’s Lumakras Plus Vectibix for KRAS G12C-Mutated Metastatic Colorectal Cancer

Image Credit: Adobe Stock Images/Sebastian Kaulitzki

The FDA has approved Amgen’s Lumakras in combination with Vectibix (panitumumab) to treat adult patients with KRAS G12C-mutated metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. According to the company, the regulatory action was based on results from the Phase III CodeBreaK 300 trial, which demonstrated that the combination significantly improved progression-free survival (PFS) compared to standard-of-care (SOC).¹

"Colorectal cancer is the third leading cause of cancer-related deaths in the United States, and fewer than one in five people diagnosed with metastatic disease survive beyond five years after diagnosis," said Jay Bradner, MD, EVP, research and development, Amgen, in a press release. "Lumakras plus Vectibix offers a targeted, biomarker-driven combination therapy that helps delay disease progression more effectively than the investigated standard of care. This new option validates our combination approach to improve outcomes for patients living with advanced KRAS G12C-mutated metastatic colorectal cancer."

The multicenter, open-label, randomized CodeBreaK 300 trial included 160 patients with KRAS G12C-mutated mCRC.1,2 Investigators compared Lumakras at doses of 960 mg and 240 mg in combination with Vectibix vs. SOC (trifluridine/tipiracil or regorafenib) in patients with KRAS G12C-mutated mCRC. The primary endpoint of the trial was improved PFS, with key secondary endpoints that included overall survival (OS) and overall response rate (ORR).

The combination treatment demonstrated a median PFS of 5.6 months compared to two months with SOC treatment. The treatment also demonstrated a 26% improved ORR compared to no improvement for SOC; however, the study was not statistically powered for OS.

Common adverse events included rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain.¹

"In metastatic colorectal cancer, KRAS mutations are historically associated with worse mortality rates and inferior outcomes compared to non-mutated tumors, and standard treatment options have shown minimal benefit," said primary study investigator Marwan G. Fakih, MD, co-director of the Gastrointestinal Cancer Program, City of Hope, in the press release. "Designed for dual blockade of KRAS G12C and EGFR pathways, the combination of sotorasib plus panitumumab provides a needed new treatment option to better overcome cancer's escape mechanisms. The CodeBreaK 300 study showed superior progression-free survival compared to the investigated standard of care and represents a clinically meaningful benefit for patients with KRAS G12C-mutated metastatic colorectal cancer."

According to the American Cancer Society, it is estimated that there will be approximately 107,320 new cases of colon cancer in 2025 and 46,950 new cases of rectal cancer in the United States. Currently, the lifetime risk of developing colorectal cancer is about one in 24 for men and one in 26 for women. It is the third-leading cause of cancer deaths in men and the fourth in women in the United States. However, it’s the second-leading cause of cancer-related deaths when combining both men and women. Overall, the disease is expected to cause an estimated 52,900 deaths by the end of the year.³ KRAS G12C mutations are found in 3%-5% of colorectal cancers.¹

"There is an immense need for continued innovation and precision medicine to help address metastatic colorectal cancer," said Michael Sapienza, chief executive officer of the Colorectal Cancer Alliance. "This new combination approach is an important breakthrough for patients with KRAS G12C-mutated metastatic colorectal cancer, offering a new beneficial treatment option for patients living with this devastating and challenging disease."

References

1. FDA APPROVES LUMAKRAS® (SOTORASIB) IN COMBINATION WITH VECTIBIX® (PANITUMUMAB) FOR CHEMOREFRACTORY KRAS G12C-MUTATED METASTATIC COLORECTAL CANCER. Amgen. January 17, 2025. Accessed January 20, 2025. https://www.amgen.com/newsroom/press-releases/2025/01/fda-approves-lumakras-sotorasib-in-combination-with-vectibix-panitumumab-for-chemorefractory-kras-g12cmutated-metastatic-colorectal-cancer

2. Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C. The New England Journal of Medicine. October 22, 2023. Accessed January 20, 2025. https://www.nejm.org/doi/full/10.1056/NEJMoa2308795

3. Key Statistics for Colorectal Cancer. American Cancer Society. Accessed January 20, 2025. https://www.cancer.org/cancer/types/colon-rectal-cancer/about/key-statistics.html