Abstract 507TiP
Background
Trilaciclib, an intravenous (IV) kinase inhibitor that protects hematopoeitic stem and progenitor cells during chemotherapy exposure, is FDA approved to decrease the incidence of chemotherapy-induced myelosuppression in patients (pts) with extensive-stage small cell lung cancer based on data from three randomized, placebo-controlled phase II trials. In another randomized phase II trial in pts with triple-negative breast cancer, administering trilaciclib prior to chemotherapy had limited myeloprotective effects, but improved overall survival (OS).
Trial design
PRESERVE 1 (NCT04607668) is a randomized, double-blind, phase III trial to evaluate the myeloprotective and antitumor effects of trilaciclib administered prior to fluorouracil (5FU), leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/bevacizumab in adult pts with previously untreated metastatic colorectal cancer. Eligible pts must have confirmed unresectable and evaluable disease, an ECOG PS of 0/1, and adequate organ function. Tumors must be mismatch repair proficient/microsatellite stable and can be of any known BRAF mutation status. Pts should have no symptomatic peripheral neuropathy, uncontrolled hypertension, or other contraindications to FOLFOXIRI/bevacizumab. Approximately 296 pts will be stratified by country, prior therapy, and BRAF V600E mutation status, and randomly assigned 1:1 to receive IV trilaciclib 240 mg/m2 or placebo on days 1 and 2 prior to FOLFOXIRI/bevacizumab in 14-day cycles for up to 12 cycles (Induction). Following Induction, pts will receive trilaciclib or placebo prior to 5FU/leucovorin/bevacizumab. Treatment will continue until disease progression, unacceptable toxicity, withdrawal, or the end of the trial. Primary endpoints are duration of severe neutropenia (SN) in cycle 1 and occurrence of SN during Induction. Key secondary endpoints are progression-free survival, OS, and time to confirmed deterioration in chemotherapy-induced fatigue during Induction. The effects of trilaciclib on red blood cell and platelet lineages will also be investigated. Recruitment began in the US in October 2020, and globally in early 2021.
Clinical trial identification
NCT04607668 Release date: 29 October 2020.
Editorial acknowledgement
Medical writing assistance was provided by Fiona Bolland, PhD, from Alligent Europe (Envision Pharma Group).
Legal entity responsible for the study
G1 Therapeutics, Inc.
Funding
G1 Therapeutics, Inc.
Disclosure
M. Aapro: Financial Interests, Personal, Advisory Role, Consultant: BMS; Celgene; Clinigen; : Eisai; Financial Interests, Personal and Institutional, Invited Speaker, Consultant: Novartis; Financial Interests, Personal, Invited Speaker, Consultant: Accord; Amgen; Genomic Health; GSK; Helsinn; Hospira; JnJ; Merck; Merck Serono; Pfizer; Pierre Fabre; Roche; Sandoz; Tesaro; Teva; Vifor; G1 Therapeutics; Lilly; Bayer Schering; Biocon; Boehringer; Cephalon; Chugai; Eisai; DrReed; Glenmark; Ipsen; OrthoBiotech; Kirin Kyowa; Sanofi; Taiho; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca; Vimanis; Non-Financial Interests, Personal, Leadership Role: MASCC; SIOG; ECCO; Non-Financial Interests, Personal, Member: ABC Global Alliance; AllCan; Other, Personal, Other, Editor: Critical Reviews in Oncology Hematology; Journal of Cancer Policy; The Oncologist; Other, Personal, Other, Editorial Board: Annals of Oncology; Journal of Supportive Care in Cancer. S. Shah: Financial Interests, Personal, Full or part-time Employment, COI relates to an immediate family member: One Oncology; Financial Interests, Personal, Leadership Role, COI relates to an immediate family member: One Oncology; Financial Interests, Personal, Stocks/Shares: One Oncology; Financial Interests, Personal, Stocks/Shares: Thymecare; Financial Interests, Personal, Advisory Role: Thymecare. A.E. Gabayan: Financial Interests, Personal, Full or part-time Employment: Beverly Hills Cancer Center; Financial Interests, Personal, Leadership Role: Beverly Hills Cancer Center; Financial Interests, Personal, Stocks/Shares: Beverly Hills Cancer Center; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: G1 Therapeutics; Financial Interests, Institutional, Principal Investigator: GSK; Financial Interests, Institutional, Principal Investigator: Jiangsu Hengrui Medicine Co., Ltd.; Financial Interests, Institutional, Principal Investigator: EMD Serono; Financial Interests, Institutional, Principal Investigator: Bayer; Financial Interests, Institutional, Principal Investigator: Constellation Pharmaceuticals; Financial Interests, Institutional, Principal Investigator: Incyte Corporation. Y. Pritchett: Financial Interests, Personal, Full or part-time Employment: G1 Therapeutics, Inc..J. Yi: Financial Interests, Personal, Full or part-time Employment: G1 Therapeutics, Inc.. J. Horton: Financial Interests, Personal, Full or part-time Employment: G1 Therapeutics, Inc..All other authors have declared no conflicts of interest.