To decrease the incidence of chemotherapy-induced myelosuppression in patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen

For extensive-stage small cell lung cancer (ES-SCLC)

STUDIED IN THREE RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED CLINICAL TRIALS

Key Endpoints Evaluated in Studies

  • COSELA™ (trilaciclib) studies were designed to determine the effects of COSELA on chemotherapy-induced myelosuppression endpoints
  • Primary endpoints: neutrophil lineage endpoints are presented for each study
    • Primary endpoints (Pivotal Study and Study 3) were the duration of severe neutropenia (DSN) in Cycle 1 and percentage of patients with severe neutropenia (SN) (occurrence) during the treatment period. SN was defined as absolute neutrophil count (ANC) <0.5 x 109 cells per L
  • Key secondary endpoints in the Pivotal Study and Study 3 included: number of all-cause dose reductions (event rate per cycle); number (%) of patients with RBC transfusion on/after 5 weeks; number (%) of patients with G-CSF administration, and in Study 3, occurrence of platelet transfusions
  • Other secondary endpoints (Pivotal Study, Study 2, and Study 3) included: number (%) of patients with Grade 3 or 4 decreased hemoglobin, rate of RBC transfusions over time, and percent of patients receiving erythropoiesis-stimulating agents (ESAs)

For exploratory Study 2, the primary objective was safety and tolerability; various efficacy analyses were prospectively defined as secondary endpoints.

Pivotal Study: 1st-Line with Etoposide/Carboplatin + Atezolizumab (E/P/A)

COSELA or placebo given prior to treatment with E/P, with atezolizumab, in patients newly diagnosed with ES-SCLC

DAY 1AtezolizumabDAY 2PlaceboPrior to E DAY 3PlaceboPrior to EDAY 1COSELAPrior to E/P AtezolizumabDAY 2COSELAPrior to EDAY 1AtezolizumabDAY 3COSELAPrior to EDAY 1PlaceboPrior to E/P AtezolizumabPatients newlydiagnosed with ES-SCLC(N=107)Treated until diseaseprogression orunacceptable toxicityRandomizedE/P/A REGIMENWITHOUT COSELA(N=53)E/P/A REGIMENWITH COSELA (N=54)In each 21-day cycleIn each 21-day cycleINDUCTION(up to four 21-day cycles)MAINTENANCE(21-day cycles) DAY 1PlaceboPrior to E/P AtezolizumabDAY 1COSELAPrior to E/P AtezolizumabPatients newlydiagnosed with ES-SCLC(N=107)DAY 2COSELAPrior to EDAY 1Atezolizumab DAY 1AtezolizumabTreated until diseaseprogression orunacceptable toxicityDAY 3COSELAPrior to ERandomizedE/P/A REGIMENWITHOUT COSELA(N=53)E/P/A REGIMENWITH COSELA(N=54)In each 21-day cycleIn each 21-day cycleINDUCTION(up to four 21-day cycles)MAINTENANCE(21-day cycles)DAY 2PlaceboPrior to E DAY 3PlaceboPrior to E
  • In both arms, it was investigator’s choice to use prophylactic G-CSF, or ESA, from Cycle 2 onward as clinically indicated
  • Investigators had the choice to use therapeutic G-CSF and RBC or platelet transfusions at any time during the study as clinically indicated
Pivotal Study Population Characteristics
Median age of 64 years (range: 45 to 83) 70% male, 97% White 14% with ECOG performance status 2
28% with a history of brain metastases 38% current smokers 46% lactate dehydrogenase (LDH) >ULN

Patients were stratified by ECOG performance status (0 to 1 vs 2) and the presence of brain metastases. Carboplatin (AUC 5) and atezolizumab (1200 mg) were administered on Day 1 and etoposide (100 mg/m2) and COSELA (240 mg/m2) or placebo were administered on Days 1, 2, and 3 of a 21-day cycle for up to a maximum of 4 cycles (induction).

Effectiveness Also EVALUATED in Two Supportive Studies

Study 2: 1st-Line with Etoposide/Carboplatin (E/P)

COSELA or placebo given prior to administration of E/P-containing regimen in patients newly diagnosed with ES-SCLC

  • A total of 77 patients were randomized to COSELA (N=39) or placebo (N=38) and stratified by ECOG performance status (0 to 1 vs 2)
  • Carboplatin (AUC 5) was administered on Day 1 and etoposide (100 mg/m2) and COSELA (240 mg/m2) or placebo were administered on Days 1, 2, and 3 of a 21-day cycle until disease progression or unacceptable toxicity
  • Supportive care was as described in the Pivotal Study

Study 3: 2nd- and 3rd-Line with Topotecan

COSELA or placebo given prior to administration of a topotecan-containing regimen in patients with ES-SCLC previously treated with chemotherapy

  • A total of 61 patients were randomized to COSELA (N=32) or placebo (N=29). Patients were stratified by ECOG performance status (0 to 1 vs 2) and sensitivity to first-line treatment
  • Topotecan (1.5 mg/m2) and COSELA (240 mg/m2) or placebo were administered on Days 1–5 of a 21-day cycle. Treatment was administered until disease progression or unacceptable toxicity
  • Supportive care was as described in the Pivotal Study

INDICATION: COSELA is indicated to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC).