- A panel of Food and Drug Administration advisers were unconvinced by clinical trial data for Amgen’s lung cancer drug Lumakras, voting 10-2 Thursday that the results could not be reliably interpreted.
- The advisers cited a range of issues in the conduct of the Phase 3 trial, called CodeBreak 200. Data released last year showed Lumakras had a small benefit over standard chemotherapy in delaying cancer progression, but early patient dropout and imaging review discrepancies raised doubts about the results’ reliability.
- Approved in 2021 for metastatic lung cancer, Lumakras was the first drug to arrive on market that targets an often mutated gene called KRAS. Its clearance is conditional, meaning Amgen needs to confirm the drug’s benefit with further testing — a box CodeBreak 200 was meant to check. The FDA will decide by December whether to grant full approval.
The negative panel vote is a setback in Amgen’s efforts to cement Lumakras’ U.S. approval, but doesn’t appear likely to result in the drug’s withdrawal from market.
Many of the advisers, in explaining their “no” votes, indicated they were ruling narrowly on the question of CodeBreak 200’s reliability, rather than delivering a verdict on Lumakras more broadly.
"I voted no, but it's not a question about the drug or what I feel about the drug, or the importance that I think it offers my community of lung cancer patients and survivors,” said James Pantelas, the committee’s patient representative.
FDA officials also indicated that they were not looking to revoke Lumakras’ accelerated approval, which was based on the drug’s ability to shrink lung tumors.
“It is not our intent to immediately withdraw a drug that has a quote unquote failed confirmatory trial,” said Harpreet Singh, director of one of the FDA’s oncology divisions. “It is under accelerated approval and there are multiple pathways [to confirming full approval] available to us.”
Still, both the FDA and the advisers were clear that they saw many issues with how CodeBreak 200 was conducted.
For example, significantly more patients enrolled to the chemotherapy arm in the trial dropped out before initiating treatment, potentially signaling they knew which group they had been assigned to. Independent reviews of tumor imaging scans also differed substantially than those by investigators, raising other questions of trial bias.
"No one expects a perfect [randomized controlled trial]. But what we hope for is a small number of issues in trial conduct and an effect large enough to withstand the uncertainties caused by those issues,” said Mark Conaway, a professor at the University of Virginia School of Medicine and a committee member.
“For this trial we seem to have the opposite: a large number of issues that cloud the interpretation of a small observed effect,” he added.
Notably, while CodeBreak 200 results showed a roughly one-month benefit in progression-free survival over chemotherapy, there was no significant difference in patients’ overall survival.
"The magnitude of effect is small — statistically significant but not clinically significant,” said Neil Vasan, an oncologist at Columbia University Medical Center and a committee member.
In a statement following the vote, Amgen said that it will “continue to progress” its testing of Lumakras and “work closely with the FDA on the full approval pathway” for the drug.
The setback could help rival Mirati Therapeutics, which sells a competing KRAS drug called Krazati that arrived to market after Lumakras. On Thursday, Bloomberg reported that Sanofi is exploring an acquisition of Mirati, shares of which rose by 45% yesterday.
Correction: This story has been updated to better reflect the question upon which the committee’s vote was based.