On September 18, 2021 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported the presentation of safety and efficacy results from Cohort 4 of the ZENITH20 clinical trial (Press release, Spectrum Pharmaceuticals, SEP 18, 2021, View Source [SID1234587930]). 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) (Free ESMO Whitepaper) Congress 2021 taking place in Paris on September 16-20, 2021.

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"The data presented in Paris from Cohort 4 is very encouraging," said Francois Lebel, M.D., Chief Medical Officer of Spectrum Pharmaceuticals. "There currently is no specific approved treatment for NSCLC patients with HER2 exon 20 insertion mutations. This data represents a significant milestone in our development of poziotinib for patients with a significant medical need."

A copy of the ESMO (Free ESMO Whitepaper) presentation titled, "Efficacy and safety of poziotinib in treatment-naïve NSCLC harboring HER2 exon 20 mutations: A multinational Phase 2 study (ZENITH20-4)" presented by Dr. Robin Cornelissen, from the Erasmus MC Cancer Institute in Rotterdam, is available on Spectrum’s corporate website at View Source

ZENITH20 Trial Design and Early Safety and Efficacy Data for Cohort 4

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.

About the ZENITH20 Clinical Trial

The ZENITH20 study consists of seven cohorts of NSCLC patients. Cohorts 1 (EGFR) and 2 (HER2) in previously treated NSCLS patients with exon 20 mutations and Cohort 3 (EGFR) in first-line patients have completed enrollment. Cohort 4 (HER2) in first-line NSCLC patients with exon 20 mutations is still enrolling patients. Cohorts 1- 4 are each independently powered for a pre-specified statistical hypothesis and the primary endpoint is objective response rate (ORR). Cohort 5 includes previously treated or treatment-naïve NSCLC patients with EGFR or HER2 exon 20 insertion mutations. Cohort 6 includes NSCLC patients with classical EGFR mutations who progressed while on treatment with first-line osimertinib and developed an additional EGFR mutation. Cohort 7 includes NSCLC patients with a variety of less common mutations in EGFR or HER2 exons 18-21 or the extracellular or transmembrane domains.