Trilaciclib vs Placebo in Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC) Receiving Topotecan

A Randomized, Double-Blind, Placebo-Controlled Study of Trilaciclib vs Placebo in Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC) Receiving Topotecan Chemotherapy

This is a multicenter, randomized, double-blind, placebo-controlled study to assess whether trilaciclib administered prior to topotecan is non-inferior to placebo administered prior to topotecan with regard to overall survival.

Study Overview

• Status: Recruiting
• Conditions: Extensive-stage Small-cell Lung Cancer
• Intervention / Treatment: Drug: Trilaciclib; Drug: Topotecan; Drug: Placebo

Detailed Description

The study will include 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. Patients randomized in this study will receive trilaciclib/placebo + topotecan 1.5 mg/m2 until disease progression, unacceptable toxicity, withdrawal of consent, Investigator decision to discontinue treatment, or the end of the trial, whichever comes first.

Trilaciclib was approved by the United States (US) Food and Drug Administration (FDA) as a treatment 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 ES-SCLC. As a post-marketing requirement, the FDA asked the Sponsor to conduct a study in patients with ES-SCLC undergoing chemotherapy to evaluate survival and disease progression following trilaciclib administration in patients treated with a platinum/etoposide-containing regimen or topotecan-containing regimen with at least 2 years of follow-up. This study is designed to fulfill this requirement.

• Study Type: Interventional
• Enrollment (Estimated): 302
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Pharmacosmos Clinical and non-clinical Department; Phone Number: +45 5948 5959; Email: info@pharmacosmos.com

Study Locations

• Spain
  • Seville, Spain
    • Recruiting
    • Hospital
    • Contact: MD, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ES-SCLC with confirmed diagnosis of SCLC by histology or cytology
2. Progression during or after prior first or second line chemotherapy. First-line regimen must have been a platinum-containing combination.
3. Measurable or evaluable disease as defined by RECIST v1.1

Exclusion Criteria:

1. History of topotecan (or other topoisomerase I inhibitor) or trilaciclib treatment for SCLC
2. Any chemotherapy, immunotherapy, biologic, investigational, or hormonal therapy for cancer treatment within 3 weeks, except for adjuvant hormonal therapy for breast cancer and prostate cancer
3. Presence of brain metastases/leptomeningeal disease requiring immediate treatment with radiation therapy or steroids
4. Radiotherapy within 2 weeks
5. History of ILD/pneumonitis
6. History of other malignancies, except for curatively treated solid tumors with no evidence of disease for ≥ 2 years or other NCS cancers

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m²; Patients randomized 1:1 to trilaciclib. Patients receive trilaciclib (240 mg/m²) administered once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients receive topotecan (1.5 mg/m²)	Drug: Trilaciclib; Participants will receive intravenous trilaciclib infusion; Other Names: G1T28; CDK 4/6 inhibitor; cyclin-dependent kinase 4/6 inhibitor; Drug: Topotecan; Participants will receive intravenous topotecan infusion; Other Names: Hycamtin
Placebo Comparator: Placebo + Topotecan 1.5 mg/m²; Patients are randomized 1:1 to placebo. Patients receive placebo administered once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients receive topotecan (1.5 mg/m²).	Drug: Topotecan; Participants will receive intravenous topotecan infusion; Other Names: Hycamtin; Drug: Placebo; Participants will receive intravenous placebo infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	To assess the effect of trilaciclib on OS compared with placebo in patients receiving topotecan	From date of randomization until date of death due to any cause for those who died; or date of last contact known as alive for those who survived in the study (censored cases), assessed up to 52 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-tumor efficacy	To assess the effect of trilaciclib on Progression Free Survival (PFS) compared with placebo in patients receiving Topotecan	From date of randomization until date of documented radiologic disease progression per RECIST v1.1 or death due to any cause, whichever comes first, assessed up to 52 months
Anti-tumor efficacy	To assess the effect of trilaciclib on objective response rate (ORR) compared with placebo in patients receiving Topotecan	From date of randomization until the occurrence of progressive disease, withdrawal of consent, or initiation of subsequent anti-cancer therapy, assessed up to 52 months
Anti-tumor efficacy	To assess the effect of trilaciclib on duration of response (DOR) compared with placebo in patients receiving Topotecan	From date of first objective response of complete response (CR) or partial response (PR) and the first date that progressive disease is objectively documented or death, whichever comes first, assessed up to 52 months
Neutrophil-related myeloprotection efficacy	Duration of severe (CTCAE Grade 4) neutropenia in Cycle 1	From date of randomization until end of cycle 1 (each cycle is 21 days)
Neutrophil-related myeloprotection efficacy	Occurrence of severe (CTCAE Grade 4) neutropenia and febrile neutropenia AEs	From date of randomization until end of treatment, assessed up to 52 months
Neutrophil-related myeloprotection efficacy	Occurrence of G-CSF administration	From date of randomization until end of treatment, assessed up to 52 months
RBC related myeloprotection efficacy	Occurrence of CTCAE Grade 3 or 4 decreased hemoglobin laboratory values and ESA administration	From date of randomization until end of treatment, assessed up to 52 months
RBC related myeloprotection efficacy	RBC transfusions on or after Week 5 (occurrence)	From date of randomization until end of Week 5
RBC related myeloprotection efficacy	RBC transfusions on or after Week 5 (number of transfusions)	From date of randomization until end of Week 5
Platelet related myeloprotection efficacy	Occurrence of CTCAE Grade 3 or 4 decreased platelet count laboratory values and Platelet transfusions (occurrence)	From date of randomization until end of treatment, assessed up to 52 months
Platelet related myeloprotection efficacy	Occurrence of CTCAE Grade 3 or 4 decreased platelet count laboratory values and Platelet transfusions (number of transfusions)	From date of randomization until end of treatment, assessed up to 52 months
Myeloprotection efficacy	Occurrence of hospitalizations due to chemotherapy-induced myelosuppression	From date of randomization until end of treatment, assessed up to 52 months
Myeloprotection efficacy	Number of hospitalizations due to chemotherapy-induced myelosuppression	From date of randomization until end of treatment, assessed up to 52 months
Chemotherapy dosing	To assess the effects of trilaciclib on chemotherapy dosing (delays) compared with placebo when administered prior to topotecan.	From the date of randomization until end of treatment, assessed up to 52 months
Chemotherapy dosing	To assess the effects of trilaciclib on chemotherapy dosing (reductions) compared with placebo when administered prior to topotecan.	From the date of randomization until end of treatment, assessed up to 52 months
Incidence of Treatment-Emergent Adverse Events as Assessed by CTCAE	To assess the effects of trilaciclib administered prior to topotecan compared with placebo administered prior to topotecan on occurrence and severity of adverse events by CTCAE, study treatment discontinuation due to adverse events, and trilaciclib adverse events of special interest	From the date of randomization until end of treatment, assessed up to 52 months

Collaborators and Investigators

• Sponsor: Pharmacosmos A/S
• Investigators: Study Director: Pharmacosmos Clinical and non-clinical Department, Pharmacosmos A/S

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2023
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): October 30, 2027

Study Registration Dates

• First Submitted: April 12, 2023
• First Submitted That Met QC Criteria: May 22, 2023
• First Posted (Actual): May 24, 2023

Study Record Updates

• Last Update Posted (Estimated): September 4, 2025
• Last Update Submitted That Met QC Criteria: August 27, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: ES-SCLC; myelosuppression; chemotherapy-induced myelosuppression; myeloprotection; chemotherapy-induced neutropenia; chemotherapy-induced anemia
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Small Cell Lung Carcinoma; Heterocyclic Compounds; Substandard Drugs; Pharmaceutical Preparations; Camptothecin; Alkaloids; Topotecan; Counterfeit Drugs; trilaciclib
• Other Study ID Numbers: G1T28-211; 2022-502357-34-00 (Other Identifier: EU-CTR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No