1742PDTrilaciclib (T) decreases myelosuppression in extensive-stage small cell lung cancer (ES-SCLC) patients receiving first-line chemotherapy plus atezolizumab

Abstract Background Chemotherapy (chemo)-induced damage of hematopoietic stem and progenitor cells (HSPC) causes multi-lineage myelosuppression. Current supportive therapies are lineage specific and administered after damage has occurred. T, a highly selective, reversible CDK4/6 inhibitor and first-in-class myelopreservation agent, preserves HSPCs during chemotherapy, improving its safety and tolerability. This trial (NCT03041311) studied the benefits of T in ES-SCLC patients receiving 1L chemo + atezolizumab (A). Methods This placebo (P)-controlled, double-blind, Ph2 study randomized (1:1) chemo-naive ES-SCLC pts with adequate organ function, ECOG 0-2, and no symptomatic brain mets, to T or P with etoposide/carboplatin/A (ECA) for four induction cycles followed by maintenance (A). Prophylactic growth factors were prohibited in cycle 1; otherwise standard supportive care was allowed. Prespecified lineage-specific endpoints assessed the effect of T on myelosuppression. Tumor response was assessed using RECIST v1.1. FACT-L and FACT-An were evaluated. Results T + ECA was well tolerated with fewer ≥ G3 AEs in T (62% overall; 50% any drug related) vs P (87%; 74%), primarily due to less heme toxicity. T improved ANC, RBC measures and SOC interventions (Table). T also delayed time to deterioration in some PRO functioning domains and anemia symptoms. T did not affect chemo efficacy as measured by ORR and PFS; OS will be presented. Table: 1742PD . Parameter, n [1] ECA + P N = 53 ECA + T N = 54 Adjusted 1-sided P- value Mean Duration (d) G4 ANC in Cycle 1[2] 4 0 Pts w G4 ANC* 26 (49%) 1 (2%) Dose reductions (per 100 cycles) ǂ 8.5 2.1 0.0195 Pts w RBC transfusions ≥ week 5* 11 (21%) 7 (13%) 0.1335 Pts w G-CSF Admin* 25 (47%) 16 (30%) 0.0686 [1] Data presented as proportion (*) or event rate (ǂ) [2] Surrogate for febrile neutropenia Conclusions Addition of T improves safety/tolerability of chemo as shown by statistically significant and clinically meaningful improvement in myelosuppression endpoints, reduction of chemo side effects, and SOC interventions and no detriment to anti-tumor efficacy. These data confirm the myelopreservation benefits of T seen in another 1L ES-SCLC trial (NCT02499770). Clinical trial identification GIT28-05: NCT03041311, EudraCT2017-000358-20. Legal entity responsible for the study G1 Therapeutics, Inc. Funding G1 Therapeutics, Inc. Disclosure D. Daniel: Research grant / Funding (institution): G1 Therapeutics; Research grant / Funding (institution): ER Squibb & sons; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingleheim; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Eli Lilly and Company; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Roche. D. Spigel: Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): G1 Therapeutics. J. Jaal: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim. L. Hart: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: G1 Therapeutics. K.D. Koynov: Honoraria (self), Honoraria (institution), Travel / Accommodation / Expenses: Roche; Honoraria (institution): Boehringer Ingelheim; Honoraria (institution): servier; Honoraria (institution): Novartis; Honoraria (institution): Merck; Honoraria (self), Honoraria (institution), Travel / Accommodation / Expenses: MSD; Honoraria (institution): Bayer; Honoraria (self), Honoraria (institution), Travel / Accommodation / Expenses: Eli Lilly; Honoraria (self), Honoraria (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Honoraria (institution), Travel / Accommodation / Expenses: Astelas; Honoraria (self), Honoraria (institution), Travel / Accommodation / Expenses: Amgen; Honoraria (institution): Intellect Pharma; Travel / Accommodation / Expenses: AstraZeneca. Z.(. Yang: Full / Part-time employment: G1 Therapeutics. S.G. Wolfe: Full / Part-time employment: G1 Therapeutics. R. Malik: Full / Part-time employment: G1 Therapeutics. S.R. Morris: Full / Part-time employment: G1 Therapeutics. J.M. Antal: Full / Part-time employment: G1 Therapeutics. All other authors have declared no conflicts of interest.