Amgen Chief Medical Officer Paul Burton, M.D., is sticking with the high dose of Lumakras for now after FDA advisers knocked down confirmatory results earlier this year, as a dose optimization study continues.
“I think we feel very confident in the dose—960 milligrams appears to be the optimal dose,” said Burton in an interview with Fierce Biotech. “We'll continue to work with regulators to optimize the pathway to full approval for Lumakras.”
A shadow has been cast over the KRAS inhibitor after FDA advisers said earlier this month that the primary endpoint of progression-free survival couldn’t be interpreted in a confirmatory trial the company had conducted. Lumakras received accelerated approval in May 2021 as a second-line treatment for patients with KRAS G12C-mutated non-small cell lung cancer.
Amgen was directed at the time to launch both the confirmatory trial and a dose optimization study. The latter trial remains ongoing, assessing whether the 960-mg dose is the right call compared to 240 mg. An update to the clinical trial record on Oct. 10 pushed the primary completion date back almost three months, from Aug. 23, 2024, to Nov. 14.
Buoying Amgen’s commitment to Lumakras—and the 960-mg dose—are new phase 3 data presented Sunday at the European Society of Medical Oncology Congress detailing the drug in combination with the company's EGFR antagonist Vectibix in patients with chemo-refractory KRAS G12C mutated metastatic colorectal cancer. Amgen says that both the 960-mg and 240-mg dose levels had a statistically significant advantage in progression-free survival compared to the investigator’s treatment of choice.
With a median follow-up of 7.8 months, progression-free survival was 5.6 months and 3.9 months for the 960-mg and 240-mg dose groups, respectively. The median progression-free survival for patients on the investigator’s choice was 2.2 months. Patients given the 960-mg Lumakras dose had a 26% objective response rate compared to 6% of patients given 240-mg. The ORR for patients on the investigator's choice of therapy was 0%.
“There is clinical effectiveness at the lower dose, but 960 had a greater effect,” Burton said.
Editor's note: This story was updated with objective response rate data.