Pozenveo (poziotinib), submitted by Spectrum Pharmaceuticals, Inc., not supported for NSCLC by the FDA Oncologic Drugs Advisory Committee

During the morning session of day 1 of this 2-day meeting, the Oncologic Drugs Advisory Committee (ODAC) was asked to review new drug application (IDRAC 34571) (NDA) 215643 for Pozenveo (poziotinib [ATC: L01EH]), from Spectrum Pharmaceuticals, Inc (Spectrum), for the treatment of patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring HER2 exon 20 insertion mutations.

Poziotinib is an irreversible tyrosine kinase inhibitor (TKI) that inhibits the activity of human epidermal growth factor receptor (EGFR) with activity against human EGFR 2 (HER2). HER2 mutations typically occur in NSCLC, causing uncontrolled tumor growth.

Spectrum is seeking accelerated approval (IDRAC 37909) for poziotinib for the treatment of patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring HER2 exon 20 insertion mutations.

The Oncologic Drugs Advisory Committee (ODAC) agreed that the associated risks did not outweigh the current benefits for new drug application (IDRAC 34571) (NDA) for Pozenveo (poziotinib), submitted by Spectrum Pharmaceuticals, Inc.

Panelists who did not support poziotinib voiced concerns about the lack of dose optimization, toxicities, and the delay in initiating the confirmatory trial for poziotinib.

The ODAC asked for clarification on whether the committee should compare poziotinib to all available therapies for NSCLC or only fully approved therapies. The FDA clarified that panelists should consider the current treatment landscape. This includes Enhertu (IDRAC 351529) (fam-trastuzumab deruxtecan-nxki), from Daiichi Sankyo, Inc, another therapy that received accelerated approval for patients with NSCLC whose tumors have activating HER2 mutations.
Regarding poor durability and toxicity, many committee members expressed concerns about the limited efficacy data and the noted side effects of poziotinib. Although there is a degree of clinical benefit, the toxicities disrupt the beneficial effects. Some panelists also noted that the toxicities counteract the benefits of poziotinib as an oral drug. Oral agents are typically preferred because patients may have fewer visits to the clinic, but those taking poziotinib may have to go to the clinic more often to manage side effects, panelists said.

The ODAC also had issues with the dosing optimization of poziotinib. The ideal dose of the drug is unclear because the trial for this application (ZENITH20) involved a different dosing regimen than the confirmatory phase 3 trial (PINNACLE). Some members remarked that the dose should have been further optimized, and that the confirmatory trial will be critical to learn more about the drug’s safety and efficacy. However, the FDA stated its concern about the sponsor’s delay in initiating the confirmatory trial, and many ODAC members agreed. Because the results from the confirmatory will not be available for the next few years, patients on the drug may experience a prolonged period of risk.