Masahiro Torasawa, Medical Oncologist at Juntendo University, shared on X:
“FDA declines to approve ivonescimab (PD-1 × VEGF) + chemotherapy for EGFR-mutated NSCLC after EGFR-TKI therapy.
Despite significant PFS improvement in the phase III HARMONi trial, the FDA issued a Complete Response Letter (CRL).
HARMONi (co-primary endpoints: PFS and OS)
- PFS: HR 0.52
- OS (primary): HR 0.79, p=0.057
- OS (updated, post-hoc): HR 0.76, nominal p=0.0151
Why the rejection?
The FDA had previously indicated that statistically significant OS improvement was necessary for approval in this setting. The FDA concluded that the PFS benefit without statistically significant OS improvement was insufficient to establish a favorable benefit – risk profile.
An important regulatory question: Other therapies for EGFR-mutated NSCLC after EGFR-TKI failure have received FDA approval based primarily on PFS benefit.
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