Phase 2
Completed N=96
Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Combination With Etoposide and Carboplatin in Extensive Stage Small Cell Lung Cancer (SCLC)
Source: ClinicalTrials.gov NCT02499770 ↗Enrolled (actual)
96
Serious AEs
26.3%
Results posted
Jul 2020
Primary outcomePrimary: Number of Participants With Dose Limiting Toxicities by Cohort in Cycle 1, Part 1 — 2; 1; 1; 0 Participants
Summary
This is a study to investigate the potential clinical benefit of trilaciclib (G1T28) in preserving the bone marrow and the immune system, and enhancing chemotherapy antitumor efficacy when administered prior to carboplatin and etoposide in first line treatment for patients with newly diagnosed extensive-stage SCLC.
The study consists of 2 parts: a limited open-label, dose-finding portion (Part 1), and a randomized double-blind portion (Part 2). Both parts include 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase begins on the day of first dose with study treatment and completes at the Post-Treatment Visit. Approximately, 90 patients will be enrolled in the study; 20 patients in the Part 1 and 70 patients in the Part 2 portion.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose Limiting Toxicities by Cohort in Cycle 1, Part 1 |
2; 1; 1; 0; 1; 1 | — |
| PRIMARY Incidence of Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Related AEs, Related SAEs, and AEs Leading to Study Drug Discontinuation in Part 1 |
12; 8; 4; 1; 10; 8 | — |
| PRIMARY Duration of Severe (Grade 4) Neutropenia in Part 2 |
8; 3 | = 0.0097 sig |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Trilaciclib in Cycle 1, Part 1 |
1240; 1570; 1620; 2260 | — |
| SECONDARY Area Under the Plasma Concentration Versus Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) for Trilaciclib in Cycle 1, Part 1 |
2560; 2280; 3110; 2960 | — |
| SECONDARY Time of Maximum Observed Concentration (Tmax) of Trilaciclib in Cycle 1, Part 1 |
0.57; 0.50; 0.52; 0.45 | — |
| SECONDARY Cmax of Etoposide and Free and Total Carboplatin in Cycle 1, Part 1 |
21.9; 20.2; 20.3; 18.8 | — |
| SECONDARY AUC0-inf of Etoposide and Free and Total Carboplatin in Cycle 1, Part 1 |
131; 146; 50.5; 137 | — |
| SECONDARY Tmax of Etoposide and Free and Total Carboplatin in Cycle 1, Part 1 |
1.08; 1.00; 0.52; 0.52 | — |
| SECONDARY Duration of Severe (Grade 4) Neutropenia in Part 1 |
6 | — |
| SECONDARY Occurrence of Severe (Grade 4) Neutropenia in Part 1 |
4; 0 | — |
| SECONDARY Occurrence of Febrile Neutropenia in Part 1 |
0; 0 | — |
| SECONDARY Duration of Grade 3/4 Neutropenia in Part 1 |
8; 8 | — |
| SECONDARY Occurrence of Grade 3/4 Neutropenia in Part 1 |
6; 3 | — |
| SECONDARY Nadir of Absolute Neutrophil Count in Cycle 1, Part 1 |
1.198; 1.653 | — |
| SECONDARY Occurrence of Granulocyte-Colony Stimulating Factor (G-CSF) Administration in Part 1 |
5; 3 | — |
| SECONDARY Occurrence of Red Blood Cell (RBC) Transfusion in Part 1 |
4; 1 | — |
| SECONDARY Change From Baseline of Hemoglobin at the End of Cycle 6, Part 1 |
-9.8; -20.1 | — |
| SECONDARY Occurrence of Erythropoietin Stimulating Agent (ESA) Administration in Part 1 |
2; 0 | — |
| SECONDARY Occurrence of Platelet Transfusion in Part 1 |
1; 0 | — |
| SECONDARY Change From Baseline of Platelet Count at the End of Cycle 6, Part 1 |
-72.6; -59.4 | — |
| SECONDARY Change From Baseline of Lymphocyte Count at the End of Cycle 6, Part 1 |
0.188; 0.067 | — |
| SECONDARY Occurrence of Dose Reduction in Part 1 |
2; 3 | — |
| SECONDARY Occurrence of Infectious SAEs in Part 1 |
2; 1 | — |
| SECONDARY Occurrence of Pulmonary Infection SAE in Part 1 |
1; 0 | — |
| SECONDARY Occurrence of IV Antibiotic Administration in Part 1 |
4; 1 | — |
| SECONDARY Time to First Major Adverse Hematologic Event (MAHE) in Part 1 |
2.6; 3.0 | — |
| SECONDARY Best Overall Tumor Response Based on Assessments in Part 1 |
0; 1; 8; 7; 0; 0 | — |
| SECONDARY Best Overall Tumor Response Based on Blinded Independent Central Review (BICR) Assessments in Part 1 |
1; 0; 6; 8; 2; 0 | — |
| SECONDARY Progression Free Survival (PFS) Based on Assessments in Part 1 |
5.3; 6.3 | — |
| SECONDARY OS in Part 1 |
10.6; 12.8 | — |
| SECONDARY Occurrence of Severe (Grade 4) Neutropenia in Part 2 |
16; 2 | — |
| SECONDARY Occurrence of Febrile Neutropenia in Part 2 |
3; 1 | — |
| SECONDARY Duration of Grade 3/4 Neutropenia in Part 2 |
8; 8 | — |
| SECONDARY Occurrence of Grade 3/4 Neutropenia in Part 2 |
30; 14 | — |
| SECONDARY Nadir of Absolute Neutrophil Count in Cycle 1, Part 2 |
0.815; 1.899 | — |
| SECONDARY Occurrence of G-CSF Administration in Part 2 |
24; 4 | — |
| SECONDARY Occurrence of RBC Transfusion in Part 2 |
9; 6; 9; 2 | — |
| SECONDARY Change From Baseline of Hemoglobin at the End of Cycle 6, Part 2 |
-25.9; -20.6 | — |
| SECONDARY Occurrence of ESA Administration in Part 2 |
2; 1 | — |
| SECONDARY Occurrence of Platelet Transfusion in Part 2 |
0; 2 | — |
| SECONDARY Change From Baseline of Platelet Count at the End of Cycle 6, Part 2 |
-32.7; -54.4 | — |
| SECONDARY Change From Baseline of Lymphocyte Count at the End of Cycle 6, Part 2 |
-0.203; 0.104 | — |
| SECONDARY Occurrence of Dose Reduction in Part 2 |
13; 3 | — |
| SECONDARY Occurrence of Infectious SAEs in Part 2 |
2; 4 | — |
| SECONDARY Occurrence of Pulmonary Infection SAE in Part 2 |
1; 4 | — |
| SECONDARY Occurrence of IV Antibiotic Administration in Part 2 |
8; 8 | — |
| SECONDARY Time to First MAHE in Part 2 |
1.0; NA | — |
| SECONDARY Best Overall Tumor Response Based on Assessments in Part 2 |
1; 0; 19; 24; 12; 9 | — |
| SECONDARY Best Overall Tumor Response Based on BICR Assessments in Part 2 |
0; 1; 23; 23; 10; 7 | — |
| SECONDARY PFS Based on Assessments in Part 2 |
5.0; 6.1 | — |
| SECONDARY OS in Part 2 |
10.6; 10.9 | — |
Eligibility Criteria
Inclusion Criteria
- Male or female subjects aged ≥18 years
- Unequivocally confirmed diagnosis of SCLC by histology or cytology, preferably including the presence of neuroendocrine features by immunohistochemistry
- At least 1 target lesion that is unirradiated and measurable by RECIST, Version 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
- Adequate organ function
Exclusion Criteria
- Prior chemotherapy for extensive-stage SCLC
- Presence of symptomatic brain metastases requiring immediate treatment with radiation therapy or steroids.
- Uncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failure
- Known history of stroke or cerebrovascular accident within 6 months prior to enrollment
- Other uncontrolled serious chronic disease or conditions that in the investigator's opinion could affect compliance or follow-up in the protocol
- Concurrent radiotherapy to any site or radiotherapy within 2 weeks prior to enrollment or previous radiotherapy to the target lesion sites (the sites that are to be followed for determination of a response)
- Receipt of any investigational medication within 4 weeks prior to enrollment
Data sourced from ClinicalTrials.gov (NCT02499770). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.