FDA ODAC Vote Indicates Benefit of Poziotinib Does Not Outweigh Risk for HER2 Exon 20 Ins+ NSCLC

The FDA’s Oncologic Drugs Advisory Committee voted against poziotinib as a treatment for patients with HER2 exon 20 insertion–mutated non–small cell lung cancer.

Poziotinib received a 9 to 4 vote by the FDA’s Oncologic Drugs Advisory Committee against its use in patients with HER2 exon 20 insertion mutation–positive non–small cell lung cancer (NSCLC) after it was determined that the agent does not provide substantial benefit relative to its risks.1

“Clearly, there is a clinical unmet need for the drug. The drug has activity, but I don’t know that it has a meaningful improvement over other drugs that, in the real world, are available to patients right now,” Scott Waldman, MD, PhD, a professor in the department of biochemistry and molecular biology and chair of the department of pharmacology and experimental therapeutics at Sidney Kimmel Medical College of the Thomas Jefferson University in Philadelphia, Pennsylvania, stated during the meeting.

A new drug application for poziotinib was accepted by the FDA for patients with advanced or metastatic NSCLC harboring HER2 exon 20 insertion mutations in February 2022.2 The application was based on data from the phase 2 ZENITH20 trial (NCT03318939) assessing the agent in previously treated HER2 exon 20 insertion–mutated NSCLC, an area with significant unmet need.2 Patients who enrolled on the trial were treated with an 16 mg oral dose of poziotinib for a 28-day cycle for a maximum of 24 months.

In a population of 90 patients, the overall response rate (ORR) was 27.8% with a median follow-up of 9.0 months. Twenty-five patients achieved a partial response. Moreover, the disease control rate (DCR) was 70.0%. Within the evaluable population, the ORR was 35.1% and DCR was 82.4%. In total, 74.4% of those in the as-treated population experienced tumor shrinkage along with 90.5% of those in the evaluable population.

Poziotinib also received fast track designation from the FDA in March 2021 for patients with HER2 exon 20 insertion–mutated NSCLC.3

“Part of it comes down to, if I have a patient before me and I could give them fam-trastuzumab deruxtecan-nxki [T-DXd; Enhertu] or I could give them poziotinib, I would probably give them [T-DXd]. There may be a role for poziotinib in patients who [progress on T-DXd], but the data are not there yet,” Anthony Sung, MD, an associate professor of medicine at Duke University School of Medicine in Durham, North Carolina, said during the meeting.


  1. Oncologic Drugs Advisory Committee (ODAC) Meeting, September 22-23, 2022 (Day 1). Streamed live September 22, 2022. Accessed September 26, 2022. https://bit.ly/3LNcW9a
  2. Spectrum Pharmaceuticals announces acceptance of new drug application filing for poziotinib. News Release. Spectrum Pharmaceuticals. February 11, 2022. Accessed September 26, 2022. https://bit.ly/3oPK3yQ
  3. FDA grants fast track designation to Spectrum Pharmaceuticals’ poziotinib. News Release. Spectrum Pharmaceuticals. March 11, 2021. Accessed September 26, 2022. https://bwnews.pr/3ljwoNf