NEW YORK – Spectrum Pharmaceuticals said on Monday after the market closed that poziotinib met its primary endpoint of objective response rate and shrunk tumors in lung cancer patients in the Phase II ZENITH20 trial.
Cohort 2 of the ZENITH20 study included 90 previously treated non-small cell lung cancer patients with HER2 exon 20 insertions. They received an oral, once daily dose of 16 mg of poziotinib, and nearly 28 percent saw their tumors shrink.
"Cohort 2 was designed to be a registrational study," Spectrum Chief Medical Officer Francois Lebel said in a call with investors yesterday. "Based on the results, we are in the process of requesting a meeting with the FDA to review the data and discuss our plans for [a new drug application] submission."
All patients had failed at least one line of prior systemic therapy, and 60 patients had failed two or more prior therapies, including chemotherapy and immunotherapy. Responses to poziotinib were assessed independently and confirmed by a central imaging laboratory.
The confirmed objective response rate was 27.8 percent. According to Lebel, lung cancer patients with HER2 exon 20 insertions tend to have much lower response rates to other HER2 or EGFR targeting treatments.
At a median follow up of 8.3 months, the median duration of response was 5.1 months, though some patients remained on treatment for more than one year. The disease control rate, including patients who experienced partial responses, complete responses, and stable disease, was 70 percent. The median progression-free survival was 5.5 months.
No new safety signals were observed, and toxicities were in line with those seen with second-generation tyrosine kinase inhibitors.
In the ZENITH20 trial, Spectrum is exploring the activity of poziotinib in seven cohorts of NSCLC patients with EGFR and HER2 exon 20 insertions and other activating mutations. The company is planning to report the results from cohort 3 later this year, which is studying poziotinib in treatment-naïve patients with EGFR exon 20 insertion-mutated NSCLC.
"We have made dosing modifications to the other cohorts in the ZENITH20 study," said Lebel. "Our expectation is that one of these new dosing paradigms will minimize dose interruption, dose modification and potentially enhance efficacies."
Spectrum previously said that poziotinib failed to meet the pre-specified primary endpoint of objective response rate in cohort 1 of ZENITH20, during which researchers investigated the drug in NSCLC patients with previously treated EGFR exon 20 insertions. The overall response rate in this subset of patients was 14.8 percent.
Because cancer patients with EGFR or HER2 exon 20 insertions are a hard-to-treat group with limited therapy options, several drugmakers are exploring agents in this setting. Takeda, for example, is exploring the efficacy of its tyrosine kinase inhibitor mobocertinib in lung cancer patients with EGFR and HER2 exon 20 insertions in a Phase II trial.
Jiangsu Hengrui Medicine's pan-HER tyrosine kinase inhibitor pyrotinib, currently being studied in a Phase II trial in China, yielded preliminary anti-tumor activity in a subgroup of NSCLC patients with various HER2 exon 20 insertion mutations.
Black Diamond Therapeutics is similarly aiming to advance a treatment option for patients with HER2 exon 20 insertions with its lead candidate BDTX-189, which irreversibly targets a spectrum of 50 cancer-driving mutations in the ErbB kinase family.