Plinabulin in combination with pegfilgrastim demonstrated a significant improvement in cycle 1 in the rate of prevention of grade 4 neutropenia due to chemotherapy treatment in patients with cancer in the phase 3 PROTECTIVE-2 trial.
Plinabulin in combination with pegfilgrastim (Neulasta) demonstrated a significant improvement in cycle 1 in the rate of prevention of grade 4 neutropenia due to chemotherapy treatment in patients with cancer in the phase 3 PROTECTIVE-2 trial (NCT03294577), announced BeyondSpring Inc, in a press release.
The combination also achieved all of the key secondary end points of the study, which included duration of severe neutropenia (DSN) and absolute neutrophil count (ANC) nadir, which were statistically significant results in comparison with pegfilgrastim alone.
“These data clearly demonstrate the potential for this combination to offer superior therapy compared to standard of care in the prevention of [chemotherapy-induced neutropenia (CIN)],” said Douglas W. Blayney, MD, professor of medicine at the Stanford University School of Medicine and the global principal investigator for plinabulin's CIN studies, in a statement. “With current therapy, Grade 4 neutropenia still occurs in more than 80% of patients after chemotherapy, primarily in Week 1 after chemotherapy, which increases Emergency Room visits and hospitalizations due to infection and febrile neutropenia. Grade 4 neutropenia is also associated with increased mortality and reduced long-term survival due to reduction, delay, or interruption of chemotherapy.”
A total of 221 patients with breast cancer were included in the double-blind, active-controlled, global PROTECTIVE-2 study. Of those enrolled, 111 were included in the combination arm and 110 were included in the pegfilgrastim-alone arm.
The improvement rate observed with plinabulin plus pegfilgrastim was 31.5% compared with 13.6% among patients treated with pegfilgrastim alone (difference, 17.90 percentage points; 95% CI, 7.13-28.66;P = .0015).
In terms of the secondary end points, DSN for cycle 1 from day 1 through 8 of the combination therapy showed an ANC of <0.5 x 109 cells/L, which was superior to what was seen with pegfilgrastim alone (P = .0065). The overall cycle 1 difference between plinabulin/pegfilgrastim and pegfilgrastim monotherapy was P = .03. The mean ANC nadir for cycle 1 with the combination compared with single-agent pegfilgrastim was shown with a P value of .0002. Also, between the combination arm and monotherapy arms, the difference in duration of profound neutropenia during cycle 1 was demonstrated with a P value of .0004.
Plinabulin in combination with pegfilgrastim also led to a lower percentage of grade 4 adverse events (AEs) compared with pegfilgrastim alone. In particular, 58.6% of the combination population had grade 4 AEs versus 80.0% of the monotherapy arm.
In the study, patients in the combination arm received the TAC regimen (docetaxel, doxorubicin, and cyclophosphamide) on day 1 in a 21-day cycle, along with plinabulin 40 mg on day 1 and pegfilgrastim 6 mg on day 2. Those who received pegfilgrastim alone had a matching dose of placebo. Plinabulin was administered in a single intravenous dose over 30 minutes a half-hour after the end of chemotherapy infusion.
The combination of plinabulin in combination with pegfilgrastim was previously granted Breakthrough Therapy designation in combination with myelosuppressive chemotherapeutic regimens to treat CIN in September of 2020. With the additional of plinabulin, which is known to treat CIN and potentially reduce chemotherapy-induced thrombocytopenia and increase circulating CD34+ cells in patients, could fill an unmet need in the field.
“We are pleased to have received Breakthrough Therapy designation from both the US FDA and China [National Medical Products Administration] for the plinabulin combination in CIN, underscoring the unmet medical need and potential benefit of the combination. We are working with regulatory agencies on the NDA submission, which is expected in Q1 2021 and have also begun preparation for commercialization. In addition to Plinabulin being developed as a treatment option for the prevention of CIN, it is also being investigated as a direct anticancer agent in a global Phase 3 trial of plinabulin plus docetaxel for non–small cell lung cancer, with final data read-out in 1H 2021,” stated Ramon Mohanlal, MD, PhD, chief medical officer and executive vice president of Research and Development at BeyondSpring.
BeyondSpring announces positive topline results from its PROTECTIVE-2 phase 3 registrational trial of plinabulin in combination with pegfilgrastim for prevention of chemotherapy-induced neutropenia. News release. BeyondSpring, Inc. November 16, 2020. Accessed November 16, 2020. https://bit.ly/3lBvlaQ