Ahead of adcomm, FDA flags 'systemic bias' in Amgen's late-stage Lumakras trial

As an FDA advisory committee gears up to discuss the data supporting Amgen’s Lumakras, a pre-meeting briefing document from the agency suggests the KRAS inhibitor might have a tough road ahead.

On Thursday, the FDA’s Oncologic Drugs Advisory Committee is set to discuss the merits of turning Lumakras’ accelerated approval into a full nod. The group will discuss Amgen's late-stage trial, called CodeBreaK 200.

In a document ahead of the discussion, the FDA highlighted several of its concerns with the study, including what it called “multiple sources of systemic bias” that bring the trial's overall adequacy into question.

“Issues in study conduct, high rates of censoring, loss of follow up of patients who withdrew consent, and potential loss of randomization may not allow for adequate analysis” of the trial’s results, the FDA staffers wrote.

As it stands, the drug is approved to treat KRAS G12C-mutated non-small cell lung cancer after one prior systemic therapy. It's an accelerated approval, so Amgen is seeking a full nod in the same indication.

Lumakras was the first FDA-approved therapy to target the mutation that was once considered “undruggable” or, as Amgen once put it, the “Achilles' heel” of lung cancer tumors.

The drug has been a growth driver for Amgen, even if its early commercial performance has disappointed at times. Last year, Lumakras generated $285 million in full-year sales.

Some trouble has been lurking. Aside from the CodeBreaK issues outlined in the briefing documents, the drug has previously been flagged for safety concerns in potential combo regimens.

Last summer, a study pairing Lumakras with either Merck's Keytruda or Roche’s Tecentriq found that patients experienced a roughly 50% rate of severe liver toxicity at grades 3 or 4. The results, while from a small study, raised questions about potential combo approaches for the drug.

Meanwhile, Mirati Therapeutics’ rival Krazati is hot on Lumakras’ tail. The therapy, which is Mirati’s first commercial product, scored an accelerated approval in the same indication late last year and is now being studied in its own Keytruda combination. So far, that combo hasn’t presented the same liver toxicity concerns.  

Krazati generated nearly $20 million in sales over the first half of 2023.