Phase III PRESERVE 1 trial of trilaciclib discontinued due to inferiority to placebo in severe neutropenia in colorectal cancer

Other clinical trials of trilaciclib in combination with different chemotherapies in patients with extensive-stage small cell lung cancer and triple negative breast cancer did not demonstrate this adverse survival signal. Given that placebo outperformed trilaciclib in these analyses of PRESERVE 1, the Company has made the decision to discontinue the colorectal (CRC) trial. The Data Monitoring Committee (DMC) has independently reached the same conclusion.

PRESERVE 1 was designed to evaluate the efficacy and safety of trilaciclib administered in addition to triplet therapy with FOLFOXIRI + bevacizumab in patients with metastatic CRC. Detailed Phase III results will be presented at an upcoming scientific congress and submitted for publication.

PRESERVE 1 achieved its co-primary endpoints showing clinically meaningful and statistically significant reductions in both occurrence of severe neutropenia during induction (placebo=20% vs. trilaciclib=1%; p<0.001) and mean duration of severe neutropenia in cycles 1 through 4 (placebo="1.3" days vs. trilaciclib="0.1" days; p><0.001). in addition, patients receiving trilaciclib had a clinically meaningful reduction in the rate of chemotherapy-induced diarrhea, including a 50% reduction in the rate of grade 3 4 diarrhea and a 30% reduction in the rate of any grade diarrhea, compared to placebo. further, patients receiving trilaciclib experienced fewer chemotherapy dose reductions and delays. other secondary measures of myeloprotection also favored trilaciclib, including reductions in febrile neutropenia (placebo="5%" vs. trilaciclib="0%)" and esa administration (placebo="7%" vs. trilaciclib="3%)."

However, despite the achievement of the co-primary endpoints and other secondary measures of myeloprotection and tolerability, early anti-tumor efficacy data, including overall response rate (ORR), favor patients receiving placebo compared to trilaciclib (61% and 50% ORRs, respectively). Given the differential in these anti-tumor efficacy metrics and the low likelihood of achieving the progression-free survival (PFS) and overall survival (OS) endpoints, G1 has made the decision to discontinue PRESERVE 1.