Spectrum Pharmaceuticals, Inc. announced the presentation of safety and efficacy results from Cohort 4 of the ZENITH20 clinical trial. This data is from 48 first-line patients with non-small cell lung cancer (NSCLC) with HER2 exon 20 insertion mutations who received 16mg of oral poziotinib once daily. These results showed a confirmed objective response rate (ORR) of 44%, as evaluated centrally by an independent image review committee using RECIST 1.1 criteria. The data was presented as a late breaker at the European Society for Medical Oncology (ESMO) Congress 2021 taking place in Paris on September 16-20, 2021. Cohort 4 of the ZENITH20 clinical trial is enrolling treatment-naïve NSCLC patients with HER2 exon 20 insertion mutations. This cohort is investigating the efficacy of poziotinib with a QD and BID (ongoing) dosing strategy. Poziotinib 16mg was administered orally once daily for the first 48 patients allowing 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 44% (95% CI:29.5-58.8%) in the 48 treated patients including one complete response. 88% of patients (42/48) showed tumor reduction with a DCR of 75%. Median DoR was 5.4 months (range 2.8-19.1+). Median PFS was 5.6 months (range 0-20.2+). 88% of patients had dose interruptions and 77% had reductions from the 16mg QD starting dose, while 13% had adverse event (AE) related discontinuations. The most common treatment related Grade = 3 AEs were rash (35%), stomatitis (20%), diarrhea (14%), and paronychia (8%). In addition, only 1 patient experienced Grade = 3 pneumonitis. Poziotinib demonstrated clinically meaningful anti-tumor activity in newly diagnosed NSCLC patients with HER2 exon 20 mutations with 16mg QD dosing. The safety profile was manageable and similar to previously seen in previous studies and other second-generation tyrosine kinase inhibitors. The 8mg BID portion of Cohort 4 is continuing to actively recruit.