Phase 3 Study Evaluating Efficacy, Safety and Pharmacokinetics of Trilaciclib In Extensive-Stage Small Cell Lung Cancer Patients Receiving Carboplatin Combined With Etoposide or Topotecan

Study Overview
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Brief Summary
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A Randomized, double-blind, placebo-controlled, multi-center Phase 3 study evaluating efficacy, safety and pharmacokinetics of Trilaciclib In Extensive-Stage Small Cell Lung Cancer Patients Receiving Carboplatin combined with Etoposide or Topotecan The study consists of 2 parts: Part 1: safety run-in and pharmacokinetics evaluation of 12 ES-SCLC patients (6 each for first line and second/third line ES-SCLC patients); Part 2: randomized, double-blind, placebo-controlled efficacy confirmation study of 80 ES-SCLC patients (stratified by first line and second/third line ES-SCLC, ECOG PS [0-1 vs 2] and brain metastases. The study includes screening period, treatment period, safety follow-up and survival follow-up.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multi-center Phase 3 Study Evaluating Efficacy, Safety and Pharmacokinetics of Trilaciclib In Extensive-Stage Small Cell Lung Cancer Patients Receiving Carboplatin Combined With Etoposide or Topotecan

Conditions
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Extensive-stage Small-cell Lung Cancer

Intervention / Treatment
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* Drug: Trilaciclib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female of ≥ 18 years old; Histology or cytology diagnosed extensive-stage small cell lung cancer ( ES-SCLC ) : Patients who plan to receive carboplatin combined with etoposide: naïve with systemic treatment (such as chemotherapy or combined immunotherapy) in the past Patients planning to receive topotecan : previously received 1/2 line chemotherapy or combined immunotherapy except for topotecan. At least one measurable lesion without radiotherapy that meets RECIST1.1 standard; Hemoglobin ≥ 90 g/L ; Neutrophil count ≥ 1.5 × 109 /L ; Platelet count ≥100 × 109 /L ; Creatinine ≤ 15 mg /L or creatinine clearance (CrCl) ≥ 60 mL/min (Cockcroft-Gault formula ) ; Total bilirubin ≤ 1.5 × upper limit of normal (ULN) ; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN or ≤ 5 × ULN (patients with liver metastases) ; Albumin ≥ 30 g/L ; ECOG PS score:0-2 ; Expected survival time ≥ 3 months ; Contraception : Women: Women with potential fertility must have a negative serum pregnancy test result at Screening, and take reliable contraceptive measures from signing informed consent to 3 months after the last administration ; Male: If a female partner has potential fertility, reliable contraceptive measures must be taken after signing the informed consent to 3 months after the last administration. Understand and sign the informed consent form. Exclusion Criteria: Symptomatic brain metastases that require local radiotherapy or hormone therapy; Other history of malignant cancer, except for: (1) clinically cured basal cell or squamous cell tumors; (2) curable: a) cervical cancer, B) prostate cancer, C) superficial bladder cancer; or ( 3 ) any solid tumor that it is clinically cured for 3 years or above; Uncontrolled ischemic heart disease or congestive heart failure with clinically significance (NYHA Class III or IV) ; Stroke or cardiovascular and cerebrovascular events within 6 months before enrollment ; Severe active infection; Potential inadequate compliance from psychological or other social factors; Other uncontrolled severe chronic disease or condition, which considered by Investigator as unsuitable for study participation; Known HIV infection, active hepatitis B (defined as HBV DNA positive) and hepatitis C (HCV RNA positive); Received radiotherapy within 2 weeks before enrollment ; Received cytotoxic or investigational drug treatment within 4 weeks, or non-cytotoxic anti-tumor treatment within 2 weeks before enrollment; For Part 1 patients, concomitant administration of strong or moderate inducer of CYP3A4 within 4 weeks before study drug, or strong inhibitor of CYP3A4 within 2 weeks before study drug; Recovery from previous toxicity of anti-tumor treatments to Level 0 or 1 (except for hair loss); Allergy to the study drugs or any of their components (Trilaciclib, etoposide, carboplatin, topotecan); Unable to act independently by legal restrictions or in the legal sense; Women who are pregnant or breastfeeding ; Other patients who are considered unsuitable to participate in the study. -

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Trilaciclib, carboplatin, etoposide<br>Trilaciclib plus Carboplatin combined with Etoposide (first line ES-SCLC patients) | Drug: Trilaciclib<br>* Group 1: Trilaciclib, carboplatin, etoposide，or Topotecan Group 2: Trilaciclib, Topotecan Group 3: Placebo, carboplatin, etoposide，or Topotecan<br>* Other names: plus Topotecan (second/third line ES-SCLC patients);|
| Placebo Comparator: Placebo, carboplatin, etoposide<br>Placebo plus Carboplatin combined with Etoposide (first line ES-SCLC patients) | Drug: Trilaciclib<br>* Group 1: Trilaciclib, carboplatin, etoposide，or Topotecan Group 2: Trilaciclib, Topotecan Group 3: Placebo, carboplatin, etoposide，or Topotecan<br>* Other names: plus Topotecan (second/third line ES-SCLC patients);|
| Active Comparator: Trilaciclib, Topotecan<br>plus Topotecan (second/third line ES-SCLC patients) | Drug: Trilaciclib<br>* Group 1: Trilaciclib, carboplatin, etoposide，or Topotecan Group 2: Trilaciclib, Topotecan Group 3: Placebo, carboplatin, etoposide，or Topotecan<br>* Other names: plus Topotecan (second/third line ES-SCLC patients);|
| Placebo Comparator: Placebo, Topotecan<br>Placebo plus Topotecan (second/third line ES-SCLC patients) | Drug: Trilaciclib<br>* Group 1: Trilaciclib, carboplatin, etoposide，or Topotecan Group 2: Trilaciclib, Topotecan Group 3: Placebo, carboplatin, etoposide，or Topotecan<br>* Other names: plus Topotecan (second/third line ES-SCLC patients);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) for part 1 study |  | At the end of Cycle 1 (each cycle is 21 days) | 
| Time to reach peak concentration (Tmax) for part 1 study |  | At the end of Cycle 1 (each cycle is 21 days) | 
| Half-life (T1/2) for part 1 study |  | At the end of Cycle 1 (each cycle is 21 days) | 
| Area under the plasma concentration versus time curve (AUC) for part 1 study |  | At the end of Cycle 1 (each cycle is 21 days) | 
| Incidence of Adverse Events (AEs) for part 1 and part 2 study |  | up to 30 days after last dose | 
| Incidence of Serious Adverse Events (SAEs) for part 1 and part 2 study |  | up to 30 days after last dose | 
| Incidence of AEs Leading to Study Drug Discontinuation for part 1 and part 2 study |  | up to 30 days after last dose | 
| Duration of severe neutropenia (SN) in Cycle 1; |  | At the end of Cycle 1 (each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of SN; |  | during chemotherapy assessed up to 6 months | 
| Incidence of red blood cell (RBC) transfusion (at and after Week 5) |  | during chemotherapy assessed up to 6 months | 
| Incidence of G-CSF treatment; |  | during chemotherapy assessed up to 6 months | 
| 4. Composite endpoints-important hematologic AEs (anyone of the followings): | All-cause hospitalization; All-cause dose reduction; Febrile neutropenia; Prolongation of Severe neutropenia (over 5 days); Infusion of red blood cell (RBC) infusion (at and after Week 5). | during chemotherapy assessed up to 6 months | 
| Incidence of Grade 3 and Grade 4 hematological toxicity; |  | during chemotherapy assessed up to 6 months | 
| Ctrough of absolute neutrophil count in each cycle; |  | during chemotherapy assessed up to 6 months | 
| Changes of absolute neutrophil count, platelet count, absolute lymphocyte count (ALC) and hemoglobin over time; |  | during chemotherapy assessed up to 6 months | 
| Incidence of ESA treatment; |  | during chemotherapy assessed up to 6 months | 
| The incidence of intravenous or oral antibiotics; |  | during chemotherapy assessed up to 6 months | 
| The incidence of serious infectious adverse events; |  | during chemotherapy assessed up to 6 months | 
| The incidence of serious adverse events of lung infection: |  | during chemotherapy assessed up to 6 months | 
| The incidence of febrile neutropenia; |  | during chemotherapy assessed up to 6 months | 
| The incidence of platelet transfusion |  | during chemotherapy assessed up to 6 months | 
| Objective response rate; |  | during chemotherapy assessed up to 6 months | 
| Disease control rate. |  | during chemotherapy assessed up to 6 months |