PRESERVE 4 (ClinicalTrials.gov identifier: NCT04863248)—a multicenter, randomized, double-blind, placebo-controlled phase II study of trilaciclib administered prior to docetaxel in patients with metastatic non–small cell lung cancer (NSCLC) in the second- and third-line setting who have previously been treated with a checkpoint inhibitor and chemotherapy—has been initiated. Antitumor efficacy and myeloprotection endpoints are being assessed in this study. Results of this study are expected in the first half of 2023.
“NSCLC is the most common type of lung cancer, accounting for nearly 85% of all diagnoses, and remains a great unmet medical need,” said Raj Malik, MD, Chief Medical Officer at G1 Therapeutics. “Despite improvements in therapy for metastatic NSCLC, including the use of PD-1 or PD-L1 inhibitors, the majority of patients ultimately progress during or after treatment with immunotherapy and chemotherapy. In addition to the need for therapies that more effectively extend overall survival, patients treated in the metastatic setting are particularly vulnerable to chemotherapy-induced myelosuppression and health-related quality of life impacts associated with systemic chemotherapy. We are exploring both potential benefits of trilaciclib in PRESERVE 4.”
Patient enrollment in PRESERVE 4 is now underway. The study will enroll approximately 146 patients, who will be randomly assigned 1:1 to receive trilaciclib or placebo prior to docetaxel on day 1 of each 21-day cycle. There will be two stratification factors for random assignment: country and Eastern Cooperative Oncology Group (ECOG) performance status. Prior treatment must include a maximum of one line of platinum-containing chemotherapy for recurrent/metastatic disease and a maximum of one line of PD-1/PD-L1 monoclonal antibody–containing regimen for recurrent/metastatic disease.
Study drugs are administered as follows: trilaciclib or placebo administered as a 30-minute intravenous (IV) infusion no more than 4 hours prior to chemotherapy on each day chemotherapy is administered, and IV docetaxel (75 mg/m2) on day 1. Treatment cycles will occur consecutively without interruption, except when necessary, to manage toxicities or for administrative reasons. Study drug administration will continue until disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 or clinical progression as determined by the investigator, unacceptable toxicity, withdrawal of consent, discontinuation by investigator, or the end of the trial—whichever occurs first. Upon discontinuation of study treatment, patients will be followed for survival.
The primary endpoint of the trial is to evaluate the antitumor effect of trilaciclib on overall survival compared to placebo. Secondary endpoints include the effect of trilaciclib on other antitumor endpoints compared to placebo, including progression-free survival, overall response rate, and duration of response, and evaluation of the multilineage myeloprotection benefit of trilaciclib compared to placebo. The safety and tolerability of trilaciclib in NSCLC will also be assessed.
