On December 26, 2019 Spectrum Pharmaceuticals, Inc. (NASDAQ-GS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported that its pre-specified primary endpoint in its Phase 2 clinical trial evaluating poziotinib in previously treated non-small cell lung cancer (NSCLC) patients with EGFR exon 20 insertion mutations was not met in Cohort 1 (Press release, Spectrum Pharmaceuticals, DEC 26, 2019, View Source [SID1234552612]). The company also announced that the Biologics License Application (BLA) for ROLONTIS(eflapegrastim) was accepted for review by the U.S. Food and Drug Administration (FDA) and set a Prescription Drug User Fee Act (PDUFA) date of October 24, 2020.
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The ZENITH20 trial’s Cohort 1 enrolled a total of 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%). The median duration of response was 7.4 months. The safety profile was in-line with othersecond-generation EGFR tyrosine kinase inhibitors.
Joe Turgeon, President and CEO of Spectrum Pharmaceuticals said, "While the response rate of Cohort 1 in this trial was lower than we expected, the positive signals observed for this cohort provide support for the continued clinical evaluation of poziotinib in this patient population with significant unmet medical need. We look forward to providing read outs from Cohorts 2 and 3 in 2020, and plan to provide an update on the overall program strategy during the first quarter of 2020 after a full evaluation of the data from Cohort 1 is completed."
The ZENITH20 trial is made up of 7 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. The futility analysis has been completed for Cohorts 2 and 3 which met their minimum threshold of responses to continue. The company expects to report results for these cohorts in 2020. Cohorts 4, 5, 6 and 7 are continuing per protocol.
"In Cohort 1, poziotinib has shown unequivocal biologic activity. Although we are disappointed by the ORR, we are highly encouraged by other measures including the disease control rate, the duration of response and the predictable safety profile," said Francois Lebel, M.D., Chief Medical Officer of Spectrum Pharmaceuticals. "A full review of Cohort 1 is underway and we plan to present the data at a future medical meeting."
The company also announced today that the FDA has accepted for review the BLA for ROLONTIS for the treatment of chemotherapy-induced neutropenia. The PDUFA target action date for the ROLONTIS BLA has been set for October 24, 2020.
"If approved, ROLONTIS could be the first novel granulocyte colony-stimulating factor (G-CSF) available to healthcare providers in over 15 years," said Joe Turgeon. "We have confidence in the future of ROLONTIS and are looking forward to potentially competing in this multibillion-dollar market."
The BLA for ROLONTIS is supported by data from two successful large pivotal Phase 3 clinical trials, ADVANCE (conducted under a SPA) and RECOVER. These trials evaluated the safety and efficacy of ROLONTIS in a total of 643 early-stage breast cancer patients for the treatment of neutropenia due to myelosuppressive chemotherapy. In both trials, ROLONTIS demonstrated the pre-specified hypothesis of non-inferiority (NI) in duration of severe neutropenia (DSN) and a similar safety profile to pegfilgrastim. ROLONTIS also demonstrated non-inferiority (NI) to pegfilgrastim in the DSN across all 4 cycles of chemotherapy (all NI p<0.0001) in both trials.
About Poziotinib
Poziotinib is a novel, oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that inhibits the tyrosine kinase activity of EGFR as well as HER2 and HER4. Importantly this, in turn, leads to the inhibition of the proliferation of tumor cells that overexpress these receptors. Mutations or overexpression/amplification of EGFR family receptors have been associated with a number of different cancers, including non-small cell lung cancer (NSCLC), breast cancer, and gastric cancer. Spectrum holds an exclusive license from Hanmi Pharmaceuticals to develop, manufacture, and commercialize poziotinib worldwide, excluding Korea and China. Poziotinib is currently being investigated by Spectrum and Hanmi in several mid-stage trials in multiple solid tumor indications.
About ROLONTIS and the ADVANCE and RECOVER Clinical Trials
The ROLONTIS ADVANCE trial was a Phase 3, multicenter, randomized, active-controlled, open label trial that enrolled 406 early-stage breast cancer patients, who received docetaxel and cyclophosphamide chemotherapy every 21 days for four cycles. Patients were randomized in a 1:1 ratio to receive eflapegrastim (n=196) or pegfilgrastim (n=210). The primary endpoint was the duration of severe neutropenia (DSN) in Cycle 1 of absolute neutrophil count [ANC] <0.5×109/L, as measured by ANC. Secondary endpoints included the DSN in Cycles 2, 3 and 4, time to ANC recovery, depth of ANC nadir and incidence of febrile neutropenia at Cycle 1. Patients with early stage breast cancer were treated on Day 1 of each of the four cycles with (adjuvant/neo-adjuvant) docetaxel and cyclophosphamide. On Day 2 of each cycle, patients received a single dose of either eflapegrastim or pegfilgrastim subcutaneously. The ADVANCE trial was conducted under a special protocol assessment (SPA) with the FDA.
The RECOVER trial was a Phase 3, multicenter, randomized, active-controlled, open label trial that enrolled 237 breast cancer patients who received docetaxel and cyclophosphamide chemotherapy every 21 days. Patients were randomized in a 1:1 ratio to receive eflapegrastim (n=118) or pegfilgrastim (n=119). The primary endpoint was the duration of severe neutropenia (DSN) in Cycle 1 of absolute neutrophil count [ANC] <0.5×109/L, as measured by ANC. Secondary endpoints included the DSN in Cycles 2, 3 and 4, time to ANC recovery, depth of ANC nadir and incidence of febrile neutropenia in Cycle 1. Patients with early stage breast cancer were treated on Day 1 of each of the four cycles with (adjuvant/neo-adjuvant) docetaxel and cyclophosphamide. On Day 2 of each cycle, patients received a single dose of either eflapegrastim or pegfilgrastim subcutaneously.