In a dramatic showdown at the FDA’s Oncologic Drugs Advisory Committee, Amgen’s hopes of elevating its oral G12C KRAS inhibitor, Lumakras, from accelerated approval to full approval in non-small cell lung cancer were dealt a harsh blow. The panel of external experts, in a tight 10-2 vote, delivered a verdict that sent shockwaves through the room.
They deemed Amgen’s Phase III confirmatory study, CodeBreaK 200, as a murky landscape for reliable interpretation, citing a laundry list of concerns. High dropout rates, a limited sample size, and suspicions of biased conduct among trial investigators clouded the PFS data’s clarity.
Mark Conaway, a committee member from the University of Virginia School of Medicine, expressed his reservations, saying, “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. For this trial, we seem to have the opposite—a large number of issues that cloud the interpretation of a small observed effect.”
However, it was clear that the question before the committee did not directly address Lumakras’ clinical effectiveness. Patient advocate James Pantelas from Michigan vented his frustration, saying, “I hated the question. It’s not a question about the drug or what I feel about the drug, or the importance that it offers my community of lung cancer patients and survivors.”
Amgen’s bid for full approval for Lumakras, initially authorized under the accelerated pathway in May 2021, hung in the balance. In their briefing document, Amgen had presented data from CodeBreaK 200, which had shown Lumakras meeting its primary endpoint with a statistically significant reduction in the risk of disease progression or death compared to docetaxel.
However, the FDA staff’s briefing document raised eyebrows. They cited concerns of “systemic bias” in CodeBreaK 200, pointing to a significantly higher dropout rate in the docetaxel group compared to the Lumakras arm, which the FDA saw as an early sign of potential systemic bias in the study.
They also highlighted early crossovers from docetaxel to Lumakras, even before assessing disease progression, and investigator assessments that could have favored the investigational intervention.
With the FDA’s decision on Lumakras’ traditional approval slated for December 24, the stage is set for a nail-biting conclusion. While the FDA is not bound to follow the advisory committee’s recommendations, the committee’s decision often carries significant weight in shaping the future of drugs like Lumakras.