The Phase III CodeBreaK 300 study returned disappointing overall survival data for Lumakras plus Vectibix in metastatic colorectal cancer, but in its approval announcement, the FDA pointed to significant improvements in progression-free survival, calling it the “major efficacy outcome” of the trial.
The FDA on Thursday agreed to expand the label of Amgen’s KRAS inhibitor Lumakras (sotorasib), opening up its use in colorectal cancer.
With the latest approval, Lumakras can now be combined with another Amgen asset, the antibody Vectibix (panitumumab), to treat adult patients with metastatic disease and who are carrying the G12C KRAS mutation. To be eligible to Amgen’s combo, patients should have previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA’s press announcement of the approval.
The FDA’s decision on Thursday comes as a slight surprise, given that the study Amgen used to support its application—the Phase III, double-blinded, open-label and controlled CodeBreaK 300—returned disappointing survival data.
In an abstract presented at the June 2024 annual meeting of the American Society of Clinical Oncology, Amgen reported that the Lumakras regimen lowered the risk of death by 17% to 30% versus an investigator’s choice of treatment—efficacy estimates that failed to reach statistical significance. The pharma in its publication pointed out that CodeBreaK 300 “was not powered to detect a statistically significant difference in [overall survival (OS)],” but the study nevertheless “showed a trend toward improved OS.”
A few months later, in October, the FDA announced that it would push back its target action date for Lumakras in its colorectal cancer indication to “allow for additional time for review of supplemental data recently submitted to the agency,” an Amgen spokesperson told Endpoints News at the time.
The FDA indicated in its press announcement on Thursday that it based its decision on progression-free survival (PFS), which it called the “major efficacy outcome” in CodeBreaK 300. The Lumakras-Vectibix combo resulted in a significant 52% improvement in median PFS versus choice standard of care, according to the regulator.
Lumakras’ label expansion comes after Amgen unveiled plans at the recently concluded 2025 J.P. Morgan Healthcare Conference to broaden its pipeline focus beyond obesity.
In an investor note on Monday, BMO Capital Markets analysts wrote that while obesity will remain one of the pharma’s priorities in 2025, “we could see the hyper focus that developed in 2024 begin to shift as we enter into the new year.” This strategic shift follows an underwhelming readout for Amgen’s MariTide in November 2024, which showed weight-loss efficacy broadly in line with that observed in current approved therapies—but fell far short of investor expectations.
Amgen still plans to take MariTide forward, with a late-stage study planned for later this year, according to the BMO note.
But the pharma is also looking beyond obesity now, according to the analysts, who pointed out that 2025 will be a “catalyst-filled year for Amgen.” In rare diseases, for instance, the company is looking toward an upcoming FDA decision date for its anti-CD-19 therapy Uplizna in IgG4-related disease. The regulator’s verdict is expected on April 4, according to the BMO analysts.
