FDA Grants Fast Track Status to Poziotinib for HER2 Exon 20–Mutated NSCLC


The FDA has granted a fast track designation to poziotinib for use in previously treated patients with HER2 exon 20 mutations.



The FDA has granted a fast track designation to poziotinib for use in previously treated patients with HER2 exon 20 mutations, according to an announcement from Spectrum Pharmaceuticals.1

The submission of a new drug application (NDA) for the agent is anticipated later this year, according to Spectrum Pharmaceuticals.

“There are currently no approved therapies to treat patients with HER2 exon 20 mutations and we are pleased that the FDA has granted fast track designation for poziotinib,” Joe Turgeon, president and chief executive officer of Spectrum Pharmaceuticals, stated in a press release. “Momentum is building to unlock the potential of poziotinib.”

Recent data from cohort 3 of the phase 2 ZENITH20 trial (NCT03318939) were presented at the 2021 ESMO TAT Virtual Congress and showed that when poziotinib was given at a daily dose of 16 mg, it elicited clinically meaningful activity in treatment-naïve patients with metastatic NSCLC with EGFR exon 20 mutations.2

The objective response rate (ORR) achieved in this patient population was 27.8% (95% CI, 18.4%-39.1%) and the disease control rate (DCR) was 86.1%. At a median follow-up of 9.2 months, 12 of 79 patients continued to receive poziotinib. The median duration of response (DOR) with the agent in this cohort was 6.5 months. Notably, 91% of patients in the intent-to-treat (ITT) population experienced tumor shrinkage with poziotinib.

Moreover, preliminary findings from cohort 5 of the trial indicated that when the agent was delivered at a twice-daily dose in patients with metastatic NSCLC who harbored EGFR or HER2 exon 20 mutations, patients experienced a reduction in toxicity.

Specifically, the toxicity rate in those who received the agent at a daily dose of 16 mg was 31% vs 21% in those given at a twice-daily dose of 8 mg. In those who received a daily dose of 12 mg vs a twice daily dose of 6 mg, the toxicity rates were 27% and 16%, respectively. Findings from cycle 1 of treatment indicated that twice-daily dosing schedules of either 8 mg or 6 mg led to a relative reduction in dose interruptions by 38% and 52%, respectively.

In July 2020, the trial was reported to meet its prespecified primary end point for cohort 2, where poziotinib was evaluated in patients with previously treated NSCLC and HER2 exon 20 insertion mutations.3

Data from the intent-to-treat analysis demonstrated that poziotinib resulted in a confirmed ORR of 27.8% (95% CI, 18.9%-38.2%). All responses experienced with the agent were confirmed by a central imaging laboratory per RECIST criteria. Moreover, the observed lower bound of 18.9% was noted to have surpassed the prespecified lower bound of 17% in this population.

The median DOR with poziotinib at a median follow-up of 8.3 months was 5.1 months in this cohort. Moreover, the DCR reported with the agent was 70%, and the median progression-free survival (PFS) was 5.5 months.

The trial is comprised of 7 independent cohorts of patients. Specifically, cohorts 1 through 4 are independently powered for a prespecified statistical hypothesis with a primary end point of ORR. Cohorts 5 to 7 are exploratory.

Earlier data from cohort 1 showed that poziotinib resulted in an ORR of 14.8% (95% CI, 8.9%-22.6%) and a DCR of 68.7% in pretreated patients with NSCLC and EGFR exon 20 insertions.4 Of the 115 patients included in the ITT population, 79 experienced disease stability or better with poziotinib. The median DOR in these patients was 7.4 months and the median PFS was 4.2 months.

Notably, 65% of patients experienced tumor reduction with poziotinib. However, because only 17 of the 115 patients experienced a partial or complete response to treatment, the primary end point of ORR was not met.

“We are actively preparing the NDA and delighted with this fast track designation,” Francois Lebel, MD, chief medical officer of Spectrum Pharmaceuticals, added in the release. “…We are optimistic about the twice daily dosing strategy and we will provide a data update at AACR in April.”


  1. FDA grants fast track designation to Spectrum Pharmaceuticals’ poziotinib. News release. Spectrum Pharmaceuticals. March 11, 2021. Accessed March 11, 2021.
  2. Sacher A, Le X, Cornelissen R, et al. Safety, tolerability and preliminary efficacy of poziotinib with twice daily strategy in EGFR/HER2 exon 20 mutant non-smell cell lung cancer. Presented at: ESMO TAT Virtual Congress; March 1-2, 2021; Virtual. Accessed March 11, 2021.
  3. Spectrum Pharmaceuticals announces positive topline results in HER2 exon 20 insertion mutations from cohort 2 of the poziotinib ZENITH20 trial. News release. July 27, 2020. Accessed March 11, 2021.
  4. Xiuning L, Goldman J, Clarke J, et al. Phase 2 study of poziotinib in NSCLC with EGFR exon 20 insertions. Presented at: 2020 American Association for Cancer Research virtual Annual Meeting I; April 27-28, 2020. Abstract CT081.
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