Phase 2 trial of trilaciclib administered prior to sacituzumab govitecan-hziy in patients with unresectable, locally advanced, or metastatic triple-negative breast cancer demonstrates encouraging reductions in adverse events.
Trilaciclib (Cosela) demonstrates potential to meaningfully reduce adverse events (AEs) when administered prior to sacituzumab govitecan-hziy (Trodelvy) in patients with unresectable, locally advanced, or metastatic triple-negative breast cancer (TNBC), according to initial data of a phase 2 trial (NCT05113966).1
Preliminary data from the trial of 18 patients showed trilaciclib to be well tolerated with a clinically meaningful on-target effect.
In this phase 2 trial, trilaciclib reduced the rates of multiple AEs vs what was previously observed with sacituzumab govitecan-hziy in the ASCENT trial (NCT02574455), including neutropenia (0% vs 6%), anemia (6% vs 34%), and thrombocytopenia (0% vs 5%).
“Though the data are preliminary, we are seeing encouraging and consistent reductions in the rate of adverse events related to use of sacituzumab govitecan-hziy when trilaciclib is administered prior to the ADC, relative to the previously published single agent safety profile of this ADC, including those related to myelosuppression,” said Raj Malik, MD, chief medical officer at G1 Therapeutics, Inc.
This study of trilaciclib is a phase 2, multicenter, open-label, single-arm, exploratory trial assessing the safety and efficacy of trilaciclib administered prior to sacituzumab govitecan-hziy in patients with unresectable, locally advanced, or metastatic TNBC.2
Patients enrolled must have received at least 2 previous treatments with at least 1 in the metastatic setting, be aged 18 years and older, have an ECOG performance status of 0-1, and adequate organ function.
There are 3 study phases: Screening phase, treatment phase, and survival follow-up phase. The treatment phase commences on the day of the first dose of study treatment and ends at the time of the safety follow-up visit.
During the treatment phase, patients will be administered trilaciclib followed by sacituzumab govitecan-hziy on days 1 and 8 of a 21-day cycle. Patients will continue to receive the study druguntil progressive disease per RECIST v1.1, clinical progression as determined by the investigator, unacceptable toxicity, withdrawal of consent, investigator decision, or the end of the study. Trilaciclib will be given to patients as a 30-minute intravenous infusion, which will be completed within 4 hours prior to the start of treatment with sacituzumab govitecan-hziy.
The primary end point of the trial is progression-free survival with secondary end points including objective response rate, clinical benefit rate, overall survival, neutrophil-related myeloprotective effects, red blood cell-related myeloprotective effects, platelet-related myeloprotective effects, safety, and tolerability.
Initial findings from the phase 2 trial showed encouraging reductions in the rates of AEs when trilaciclib was administered prior to sacituzumab govitecan-hziy. Any grade treatment-emergent AEs were fatigue (44% in the phase 2 trial vs 52% in the ASCENT trial), nausea (39% vs 62%), constipation (28% vs 37%), diarrhea (28% vs 65%), headache (28% vs 18%), neutropenia (22% vs 64%), decreased appetite (22% vs 28%), and leukopenia (17% vs 17%).
Grade 3 or 4 adverse events which occurred in both trials included neutropenia (17% vs 52%) and leukopenia (17% vs 10%). Then, grade 3 or 4 fatigue, nausea, constipation, diarrhea, headache, and decreased appetite only occurred in the ASCENT trial.
“We believe we are seeing on-target effects of trilaciclib in the expected reduction in the rate of myelosuppression and in the rates of diarrhea and potentially alopecia. We will continue to progress this trial and look forward to presenting a more comprehensive data set including initial efficacy results at a medical meeting in the second quarter of 2023,” added Malik, in the press release.