BACKGROUND: Chemotherapy-induced damage of hematopoietic stem and progenitor 
cells (HSPC) causes multi-lineage myelosuppression. Trilaciclib is an 
intravenous CDK4/6 inhibitor in development to proactively preserve HSPC and 
immune system function during chemotherapy (myelopreservation). Preclinically, 
trilaciclib transiently maintains HSPC in G1 arrest and protects them from 
chemotherapy damage, leading to faster hematopoietic recovery and enhanced 
antitumor immunity.
PATIENTS AND METHODS: This was a phase Ib (open-label, dose-finding) and phase 
II (randomized, double-blind placebo-controlled) study of the safety, efficacy 
and PK of trilaciclib in combination with etoposide/carboplatin (E/P) therapy 
for treatment-naive extensive-stage small-cell lung cancer patients. Patients 
received trilaciclib or placebo before E/P on days 1-3 of each cycle. Select end 
points were prespecified to assess the effect of trilaciclib on myelosuppression 
and antitumor efficacy.
RESULTS: A total of 122 patients were enrolled, with 19 patients in part 1 and 
75 patients in part 2 receiving study drug. Improvements were seen with 
trilaciclib in neutrophil, RBC (red blood cell) and lymphocyte measures. Safety 
on trilaciclib+E/P was improved with fewer ≥G3 adverse events (AEs) in 
trilaciclib (50%) versus placebo (83.8%), primarily due to less hematological 
toxicity. No trilaciclib-related ≥G3 AEs occurred. Antitumor efficacy assessment 
for trilaciclib versus placebo, respectively, showed: ORR (66.7% versus 56.8%, 
P = 0.3831); median PFS [6.2 versus 5.0 m; hazard ratio (HR) 0.71; P = 0.1695]; 
and OS (10.9 versus 10.6 m; HR 0.87; P = 0.6107).
CONCLUSION: Trilaciclib demonstrated an improvement in the patient's 
tolerability of chemotherapy as shown by myelopreservation across multiple 
hematopoietic lineages resulting in fewer supportive care interventions and dose 
reductions, improved safety profile, and no detriment to antitumor efficacy. 
These data demonstrate strong proof-of-concept for trilaciclib's 
myelopreservation benefits.
CLINICAL TRAIL NUMBER: NCT02499770.