Trilaciclib trial in colorectal cancer halted after early efficacy data favor placebo
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A phase 3 trial of trilaciclib in combination FOLFOXIRI and bevacizumab for patients with metastatic colorectal cancer met its co-primary endpoints but will be terminated based on early efficacy data, according to the agent’s manufacturer.
The pivotal randomized, placebo-controlled PRESERVE 1 trial of trilaciclib (Cosela, G1 Therapeutics) achieved its primary endpoints related to severe neutropenia when added to the 5-FU-based chemotherapeutic backbone, topline results showed. However, overall response rate and preliminary survival measures favored the placebo arm of the trial.
Researchers did not observe such adverse survival signals in trials of the agent plus chemotherapies for patients with triple-negative breast cancer and extensive-stage small cell lung cancer, G1 Therapeutics stated in a press release.
PRESERVE 1 included 326 patients with metastatic colorectal cancer who received first-line trilaciclib or placebo and triplet therapy consisting of FOLFOXIRI (5-FU, folinic acid, oxaliplatin and irinotecan) and bevacizumab (Avastin, Genentech).
Topline results showed the trial achieved its co-primary endpoints, with clinically meaningful and statistically significant reductions in rates of severe neutropenia during induction (20% with placebo vs. 1% with trilaciclib; P < .001) and mean duration of severe neutropenia in cycles 1 to 4 (1.3 days vs. 0.1 days; P < .001). Patients in the trilaciclib group also had clinically meaningful reductions in rates of chemotherapy-induced diarrhea (50% for grade 3 to grade 4; 30% for any grade), as well as fewer chemotherapy dose reductions and delays. Secondary measures of myeloprotection also favored trilaciclib vs. placebo, such as reductions in febrile neutropenia (0% vs. 5%) and erythropoiesis-stimulating agent administration (3% vs. 7%), according to the press release.
Early antitumor efficacy results, however, favored placebo, including ORR (61% vs. 50%). These results and “the low likelihood of achieving the PFS and OS endpoints” prompted G1 to discontinue the trial, the press release stated.
“This study reaffirms that trilaciclib is a highly effective drug for myeloprotection that all but eliminated neutropenia as a concern for patients with [colorectal cancer] in the trial, which helps inform our ongoing combination studies with other highly myelotoxic regimens like [antibody-drug conjugates],” Raj Malik, MD, chief medical officer of G1 Therapeutics, said in a press release. “Unfortunately, despite the robust myeloprotection and improved tolerability, early survival indicators, including the observed overall response rate in this trial, favor patients receiving placebo. These results in PRESERVE 1 are inconsistent with what we’ve observed in other tumors with different chemotherapy backbones. As a result of these topline results, we have made the decision to terminate this study.”
The data monitoring committee also independently concluded that the colorectal cancer trial should be discontinued. Further results of PRESERVE 1 will be presented at a medical meeting.
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