On April 28, 2020 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported an update on its ZENITH20 Phase 2 clinical trial evaluating poziotinib in non-small cell lung cancer (NSCLC) patients with EGFR and HER2 exon 20 insertion mutations (Press release, Spectrum Pharmaceuticals, APR 28, 2020, View Source [SID1234556666]). The protocol has been amended to explore additional twice daily dosing regimens as well as lower single daily dosage amounts. Earlier use of corticosteroids has also been added to the protocol in an effort to help patients better tolerate poziotinib and stay on therapy for a longer time. Previously announced results for Cohort 1 of the SPECTRUM20 trial were presented yesterday during the oral plenary of the Lung Cancer Targeted Therapy session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting. Although the results for Cohort 1 did not meet the primary endpoint, as previously announced, poziotinib demonstrated a positive treatment effect with a 68.7% disease control rate.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"Based on our analysis of the data, we believe that dose reductions and interruptions may have negatively impacted the treatment effect of poziotinib in this trial, and we are moving forward to further test this hypothesis with additional dose exploration in various cohorts. Pharmacologic modeling suggests that BID dosing can significantly lower Cmax, potentially reducing toxicity, and at the same time, maintain serum concentration above the IC50 value, therefore retaining anti-tumor activity," said Francois Lebel, M.D., Chief Medical Officer of Spectrum Pharmaceuticals. "Cohort 5 already included lower daily doses of poziotinib and we now have added twice daily regimens with a goal of providing a greater therapeutic window. Additionally, we are incorporating earlier use of corticosteroids for better control of the observed treatment related rash."
"Our data clearly shows that poziotinib produces a positive treatment effect and we are exploring changes in its dosing to allow patients to stay on drug longer and therefore derive the full potential benefits of treatment," stated Joe Turgeon, CEO of Spectrum Pharmaceuticals. "These seriously ill cancer patients urgently need alternative treatment options."
ZENITH20 Trial Design and Results from Cohort 1
Cohort 1 of the ZENITH20 trial enrolled 115 patients who received 16 mg/day of poziotinib. The intent-to-treat analysis showed that 17 patients had a response (by RECIST) and 62 patients had stable disease for a 68.7% disease control rate (DCR). The confirmed objective response rate (ORR) was 14.8% (95% Confidence Interval (CI) 8.9%-22.6%). Based on the FDA reviewed protocol, an observed ORR of 30%, with 17% as the lower bound for 95% CI was considered to be the clinically meaningful efficacy in our study. The median duration of response was 7.4 months with progression free survival of 4.2 months.
The safety profile was in-line with the type of adverse events seen with other second-generation EGFR tyrosine kinase inhibitors. Approximately 63% of patients experienced a grade 3 or 4 adverse event, the most common of which was rash and diarrhea. Tolerability may have led to reduced drug exposure as 68% of patients were dose reduced and 88% of patients had a temporary drug/dosing interruption. The median relative dose intensity was 72%. The high incidence of dose reductions and interruptions may indicate that the once daily starting dose of 16 mg was high and the resulting reduced dose intensity could have impaired the efficacy results. The company believes that a reduction in dose interruptions and daily dosing could lead to a greater number of deeper and more durable responses.
Cohort 5 is evaluating patients using a range of different doses compared to Cohort 1. Patients are randomized to 10, 12 or 16 mg administered once daily, and with the amended protocol, the trial will also explore 6 and 8 mg administered twice daily. Cohorts 4, 6 and 7 have also been amended to use 8 mg twice daily dosing.
The ZENITH20 trial is made up of seven independent cohorts. Cohorts 1 – 4 are each independently powered for a pre-specified statistical hypothesis with a primary endpoint of ORR. Cohorts 5 – 7 are exploratory studies. Cohort 3 is now fully enrolled and the company expects to report results for Cohort 2 in mid-2020 and Cohort 3 by the end of the year.
Conference Call and Webcast
Spectrum’s management will host a webcast and conference call today, April 28, 2020 at 8:30 a.m. ET / 5:30 a.m. PT to review the data and program strategy. The live call may be accessed by dialing (877) 837-3910 for domestic callers and (973) 796-5077 for international callers and entering the conference ID#: 5536065. A live webcast of the call will be available from the Investors and Media section of the company’s website at View Source and will be archived there shortly after the live event.