Initial findings from a phase 2 trial showed trilaciclib given before sacituzumab govitecan-hziy lessened the severity of adverse effects in patients with unresectable locally advanced or metastatic triple-negative breast cancer.
Patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who received trilaciclib (Cosela) prior to sacituzumab govitecan-hziy (Trodelvy) tolerated treatment well, indicating that the agent could reduce adverse effects (AEs), according a press release from G1 Therapeutics on initial data from a phase 2 trial (NCT05113966).1
Of the first 18 patients enrolled on the trial, a clinically meaningful, on-target reduction of multiple AEs by over 50% compared with previous findings published in the phase 3 ASCENT trial (NCT05113966).2 These AEs included myelosuppression such as neutropenia, anemia, and thrombocytopenia, as well as diarrhea and potentially alopecia, which may be related to CDK4/6 expressing cells in the intestinal crypt and hair follicles.
“Though the data are preliminary, we are seeing encouraging and consistent reductions in the rate of [AEs] related to the use of sacituzumab govitecan-hziy when trilaciclib is administered prior to the ADC [antibody drug conjugate], relative to the previously published single-agent safety profile of this ADC, including those related to myelosuppression,” Raj Malik, MD, chief medical officer at G1 Therapeutics, said in the press release. “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.”
In the study, patients received trilaciclib for 30-minute intravenous infusions starting within 4 hours prior to the start of sacituzumab on days 1 and 8 of each 21-day cycle. The primary end point was to evaluate the anti-tumor efficacy of trilaciclib when administered before sacituzumab which will be measured by progression-free survival. Key secondary end points included objective response rate, duration of objective response, clinical benefit rate, overall survival, and evaluation of myeloproliferative effects of trilaciclib.
Grade 3/4 treatment-emergent adverse effects (TEAEs) in the combination arm of included neutropenia (17%) and leukopenia (17%). For reference, high-grade TEAEs for sacituzumab govitecan alone as observed in the ASCENT trial included neutropenia (52%), diarrhea (11%), and leukopenia (10%). Moreover, treatment-related AEs (TRAEs) observed with sacituzumab alone in the ASCENT trial included anemia (8%), febrile neutropenia (6%), and thrombocytopenia (2%). There were no reports of high-grade anemia, febrile neutropenia, or thrombocytopenia in the phase 2 study in patients who were pretreated with trilaciclib.
To be included in the trial, patients must have measurable disease, documentation of histology, and document progression during or after the 2 lines of systemic therapy. Additionally, patients must have an ECOG performance status of 0 or 1 and adequate organ function.
If patients had prior treatment with trilaciclib or sacituzumab, known brain metastases at enrollment, Gilbert’s disease, or who were known to be homozygous for the UGT1A1*28 allele were not eligible to enroll on the study. Bone-only disease, malignancies other than TNBC, a history of gastrointestinal issues, and a receipt of high-dose corticosteroids within 2 weeks of the first dose of study treatment were also not able to enroll.