Amgen faces a critical juncture with its pioneering KRAS inhibitor, Lumakras, as uncertainties loom over its potential combinability with standard PD-1 inhibitors and the need to defend its accelerated approval. The FDA is scheduled to convene an advisory committee meeting on October 5th to deliberate Amgen’s bid to transition Lumakras’ accelerated approval into a full-fledged endorsement, according to a government filing.
Initially granted accelerated approval in May 2021, Lumakras marked a milestone as the first KRAS inhibitor greenlit for treating KRAS G12C-mutated non-small cell lung cancer (NSCLC) after a prior systemic therapy. This pivotal decision was grounded in tumor response data from the CodeBreaK 100 trial.
Related: Advancing Precision Oncology: Targeting KRAS Mutations With LUMAKRAS And KRAZATI
The upcoming FDA meeting will pivot around fresh insights from the Phase 3 CodeBreaK 200 trial. Although Amgen refrains from speculating on the precise queries posed by the FDA’s external experts, these discussions are expected to shed light on the drug’s benefit-risk profile.
Results from the CodeBreaK 200 trial have stirred debates, particularly regarding Lumakras’ efficacy. While the treatment demonstrated a 34% reduction in the risk of disease progression or death compared to chemotherapy docetaxel, it merely extended patients’ median progression-free survival (PFS) time by an additional 1.1 months, totaling 5.6 months in the Lumakras arm. These figures fell short of those reported in the CodeBreaK 100 trial.
Notably, the survival rates between the treatment and chemotherapy groups exhibited no significant difference. Although Amgen argued that the trial wasn’t designed for an overall survival analysis, the decision to trim planned trial enrollment post the CodeBreaK 100’s favorable outcome raised ethical concerns.
Amid these considerations, Amgen is under the FDA’s scrutiny to assess a lower daily dose of Lumakras, specifically 240 mg, in comparison to the approved 960-mg strength. While data on this dose optimization study remain undisclosed, Amgen has included these findings in its application for full approval.
Related: Mirati’s KRAS Inhibitor Krazati Faces Rejection In Europe
The Lumakras saga faces not only efficacy concerns but also a liver safety signal discovered last year. The prospect of potential liver toxicity when combining Lumakras with PD-1/L1 inhibitors has cast doubts on its long-term market viability.
In the competitive landscape, Lumakras competes with Mirati Therapeutics’ Krazati. While Krazati boasts more favorable liver safety data and promising efficacy analysis, Mirati has outlined plans to assess Krazati in tandem with Keytruda for newly diagnosed KRAS G12C-mutated NSCLC patients exhibiting high PD-L1 expressions.
As the curtain rises on the FDA advisory committee meeting, the fate of Lumakras hangs in the balance, leaving the biopharmaceutical community closely watching the deliberations that could reshape the landscape of NSCLC treatments.
