Trial in progress: A phase 3, randomized, double-blind trial of trilaciclib versus placebo in patients receiving first- or second-line gemcitabine and carboplatin for locally advanced unresectable or metastatic triple-negative breast cancer (PRESERVE 2).
Authors: Goel Shom , O'Shaughnessy Joyce , Tan Antoinette R. , Krastev Boris Milev , Rugo Hope S. , Aftimos Philippe Georges , Yardley Denise A. , Zoran Andric , Wolfgang Curt Douglas , Sorrentino Jessica , Tao Wenli , Beelen Andrew Paul , Malik Rajesh K. , Jain Sarika 
Published: June 2021

TPS1107 Background: Trilaciclib is an intravenous (IV), highly potent and selective, reversible cyclin-dependent kinase (CDK) 4/6 inhibitor that protects hematopoietic stem and progenitor cells during chemotherapy (myeloprotection) and may directly enhance antitumor immunity (anticancer efficacy). In a randomized phase 2 trial of trilaciclib administered prior to gemcitabine and carboplatin (GC) versus GC alone in advanced/metastatic triple-negative breast cancer (mTNBC), although the primary endpoint of myeloprotection was not met, the addition of trilaciclib resulted in a substantial improvement in median overall survival (OS; 19.8 months with trilaciclib vs 12.6 months with placebo, hazard ratio [95% CI] = 0.37 [0.21–0.63]; O’Shaughnessy et al. SABCS 2020 [PD1-06]). Clinically meaningful improvements in OS and progression-free survival (PFS) were also observed in both programmed death ligand-1 (PD-L1)–positive and –negative subsets. Methods: The PRESERVE 2 trial (EudraCT: 2020-004930-39) is a randomized, double-blind, placebo-controlled, international phase 3 trial evaluating the efficacy of trilaciclib administered prior to GC in patients with mTNBC. Two mTNBC patient populations will be studied and analyzed separately: cohort 1 (N = 170) will evaluate first-line, PD-1/PD-L1 inhibitor–naïve patients with ≥6 months between completion of last curative treatment and first recurrence; cohort 2 (N = 80) will evaluate second-line PD-L1–positive patients following ≥4 months of PD-1/PD-L1 inhibitor therapy in the advanced setting. Key eligibility criteria for both cohorts include age ≥18 years, Eastern Cooperative Oncology Group performance status of 0/1, and available tumor tissue. Patients will be randomized (1:1) to trilaciclib 240 mg/m2 or placebo prior to gemcitabine 1000 mg/m2 and carboplatin area under the curve 2 IV on days 1 and 8, every 21 days. Stratification factors (cohort 1 only) include tumor PD-L1 status by Ventana SP-142 IVD assay, disease-free interval, and country. Study treatment will continue until progressive disease per RECIST v1.1, unacceptable toxicity, or investigator/patient decision, after which, patients will be followed every 3 months for survival. Up to 80 patients will be consented for optional paired baseline and on-treatment biopsies. Archival tissue and serial peripheral blood will be collected from all patients. The primary endpoint is OS, and the key secondary endpoint is time to confirmed deterioration in fatigue. Other secondary endpoints include PFS, myeloprotection, and safety/tolerability. Exploratory endpoints will assess pharmacodynamic parameters, including those related to immune-based mechanisms, and efficacy by CDK4/6-dependence signatures. Study enrollment is open. Clinical trial information: 2020-004930-39 .