FDA Grants Fast Track Designation to Poziotinib for HER2 exon 20–mutant NSCLC

March 15, 2021
Audrey Sternberg

Based on promising responses seen across several clinical trials of poziotinib in patients with non–small cell lung cancer and exon 20 mutations in HER2, the FDA granted the therapy fast track designation.

The investigational epidermal growth factor inhibitor poziotinib was granted fast track designation by the FDA as therapy for patients with non–small cell lung cancer (NSCLC) whose tumors harbored HER2 exon 20 mutations, according to Spectrum Pharmaceuticals who is responsible for developing the agent.1

This designation is granted to medications in order to facilitate and expedite their development and review to become available to treat patients who might not otherwise have a viable systemic therapy option.

“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 CEO of Spectrum Pharmaceuticals, said in a press release. “Momentum is building to unlock the potential of poziotinib.”

Previously, a single-center trial (NCT03066206) conducted at MD Anderson Cancer Center showed a higher rate of confirmed responses at 43% in patients with heavily pretreated EGFR or HER2 exon 20–mutant disease who received poziotinib therapy. Responses were seen regardless of if patients were refractory or naïve to therapy with other tyrosine kinase inhibitors.2

A recent presentation at the European Society for Medical Oncology Targeted Anticancer Therapies (ESMO TAT) Virtual Congress 2021 held March 1-2, 2021, detailed the results of 2 cohorts explored in the ZENITH20 trial (NCT03318939) of poziotinib in patients with NSCLC and mutations in exon 20 in either EGFR and HER2. Cohorts 2 and 4 of the trial are specifically for the assessment of patients with HER2 exon 20 mutations and previously treated or treatment-naïve disease, respectively, with the latter still open to enrollment. The primary end point of the trial is objective response rate with secondary outcomes of disease control rate, duration of response, and progression-free survival.3

The presentation at ESMO TAT focused on the results of cohort 5, which comprised 40 patients harboring EGFR or HER2 exon 20 mutations in randomized arms of poziotinib at 10, 12, or 16 mg daily and at 6 or 8 mg twice daily. Responses were observed across the dose levels, with a trend towards higher antitumor activity seen in the twice-daily administration arms.

“We are actively preparing the [new drug application] and delighted with this fast track designation,” Francois Lebel, MD, Chief Medical Officer of Spectrum Pharmaceuticals, said in a press release. “Last week, we presented at the European Society for Medical Oncology Targeted Anticancer Therapies Virtual Congress 2021 that twice daily dosing (BID) suggests improved anti-tumor activity and reduced toxicity relative to once daily dosing. We are optimistic about this BID strategy and we will provide a data update at [American Association for Cancer Research Annual Meeting] in April.”

References:

1. FDA Grants Fast Track Designation to Spectrum Pharmaceuticals’ Poziotinib. News Release. Spectrum Pharmaceuticals. March 11, 2021. Accessed March 15, 2021. https://bwnews.pr/3ljwoNf

2. Heymach J, Negrao M, Robichaux J, et al. A phase II trial of poziotinib in EGFR and HER2 exon 20 mutant non-small cell lung cancer (NSCLC). J Thoracic Oncol. 2018;13(suppl 10; abstr OA02.06). doi: 10.1016/j.jtho.2018.08.243

3. Safety, tolerability and preliminary efficacy of poziotinib with twice daily strategy in EGFR/HER2 Exon 20 mutant non-small cell lung cancer (ID 274). Ann Oncol. Presented at: European Society for Medical Oncology Targeted Anticancer Therapies (ESMO TAT) Virtual Congress 2021; March 1-2, 2021. Virtual. Abstract 36MO.