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  • FDA Approves Lumakras Combo for mCRC
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FDA Approves Lumakras Combo for mCRC

Read time: 2 mins
Published:18th Jan 2025
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Amgen announced that the FDA  has approved Lumakras  (sotorasib) in combination with Vectibix (panitumumab) for the treatment of adult patients with KRAS G12C-mutated metastatic colorectal cancer (mCRC), as determined by an FDA-approved test, who have received prior fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy. 

Approval is based on the pivotal Phase III CodeBreaK 300 study, which demonstrated that Lumakras plus Vectibix is the first and only targeted treatment combination for chemorefractory KRAS G12C-mutated mCRC to show superior progression-free survival (PFS) compared to the investigated standard-of-care (SOC) (which included trifluridine/tipiracil or regorafenib).

The CodeBreaK 300 trial enrolled 160 participants and compared  Lumakras  (sotorasib) at doses of 960 mg and 240 mg in combination with Vectibix (panitumumab) to investigator's choice of standard of care (trifluridine/tipiracil or regorafenib) in patients with chemorefractory KRAS G12C-mutated metastatic colorectal cancer (mCRC). The study met its primary endpoint showing improved progression-free survival (PFS), and the key secondary endpoints of overall survival (OS) and overall response rate (ORR) also favored the combination. 

The CodeBreaK 300 clinical trial compared Lumakras   at two different doses (960 mg daily or 240 mg daily) in combination with Vectibix to the investigator's choice of SOC (trifluridine and tipiracil or regorafenib) in patients with chemorefractory KRAS G12C-mutated mCRC. Study results demonstrated that Lumakras   960 mg daily plus Vectibix (n=53) showed an improved median PFS of 5.6 months (4.2, 6.3) compared to 2 months (1.9, 3.9) on investigator's choice of care (n=54), with a hazard ratio (HR) of 0.48 (95% Confidence Interval [CI]: 0.3, 0.78) and a p-value of 0.005. The study demonstrated an improved overall response rate (ORR) of 26% (95% CI: 15, 40) compared to 0% with investigator's choice (95% CI: 0, 7). The study was not statistically powered for overall survival (OS). The median overall survival (mOS) for patients treated with Lumakras   plus Vectibix was not reached (NR) (8.6, NR), and mOS for patients treated with investigator's choice was 10.3 months (7, NR), with a HR of 0.7 (95% CI: 0.41, 1.18); the final analysis of OS was not statistically significant. Safety profiles were consistent with those historically observed for Lumakras   and Vectibix. The most common adverse reactions (≥20%) are rash (87%), dry skin (28%), diarrhea (28%), stomatitis (26%), fatigue (21%) and musculoskeletal pain (21%). PFS of Lumakras   240 mg daily plus Vectibix (n=53) compared to investigator's choice was not statistically significant.

The KRAS G12C mutation is present in approximately 3-5% of colorectal cancers as determined by an FDA-approved biomarker test. This emphasizes the important role of comprehensive biomarker testing in mCRC. By detecting an actionable mutation, eligible patients are now able to receive a corresponding targeted therapy that may lead to improved responses.

"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 Dr. Marwan G. Fakih, primary study investigator and co-director of the Gastrointestinal Cancer Program, City of Hope. "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."

"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, executive vice president of Research and Development at Amgen."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."

Condition: Colorectal Cancer/KRAS mutated
Type: drug
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