Positive data for poziotinib in first-line NSCLC patients with HER2 Exon 20 insertion mutations.-Spectrum Pharma.

These results showed a confirmed objective response rate (ORR) of 41% (95% CI:30%-54%), as evaluated centrally by an independent image review committee using RECIST 1.1 criteria. The evaluable patient population showed an ORR of 50%. The study met its primary endpoint as the observed lower bound of 30% exceeded the pre-specified lower bound of 20%. The safety profile was consistent with the TKI class. The data is part of an oral presentation at the European Society for Medical Oncology Targeted Anticancer Therapies (ESMO TAT) Congress 2022 being held virtually March 7-8, 2022.

“Cohort 4 from our ZENITH 20 study demonstrated positive results for treatment naïve lung cancer patients harboring HER2 Exon 20 insertion mutations. There is currently no approved treatment for NSCLC patients with these mutations,” said Francois Lebel, M.D., Chief Medical Officer of Spectrum. “We are encouraged by these findings and look forward to further discussions with the FDA on the regulatory path forward.”

Safety and Efficacy Data for Cohort 4 of the ZENITH20 Clinical Trial : Cohort 4 enrolled treatment-naïve NSCLC patients with HER2 exon 20 insertion mutations. This cohort investigated the efficacy of poziotinib and included patients dosed either with a QD or BID dosing strategy. Poziotinib 16 mg was administered orally once daily for the first 48 patients followed by an additional 22 patients dosed at 8 mg twice daily. Both dosing regimens allowed dose reductions/interruptions for toxicity. The primary endpoint was ORR evaluated centrally by an independent image review committee using RECIST 1.1 criteria. Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) and safety. The primary endpoint of ORR was 41% (95% CI:30-54%) in the 70 treated patients including one complete response. The DCR was 73% (95% CI:61-83%). DoR was 5.7 months (range 1.2-19.1+). Median progression free survival (PFS) was 5.6 months (range 0-20.2+). 90% of patients had dose interruptions and 79% had reductions from the 16 mg QD starting dose, while 64% had reductions from the 8mg BID starting dose. The most common treatment related Grade greater than 3 adverse events were rash (30%), stomatitis (19%), diarrhea (14%), and paronychia (7%). In addition, the incidence of Grade greater than 3 pneumonitis was low at 3%. The safety profile was consistent with the TKI class and tolerability, dose reductions and interruptions were less frequent with BID dosing.

“Cohort 4 from our ZENITH 20 study demonstrated positive results for treatment naïve lung cancer patients harboring HER2 Exon 20 insertion mutations. There is currently no approved treatment for NSCLC patients with these mutations,” said Francois Lebel, M.D., Chief Medical Officer of Spectrum. “We are encouraged by these findings and look forward to further discussions with the FDA on the regulatory path forward.”