Carboplatin, Etoposide, and Atezolizumab With or Without Trilaciclib (G1T28), a CDK4/6 Inhibitor, in Extensive-Stage SCLC

NCT ID: NCT03041311

Last Updated: 2025-09-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-29
• Study Completion Date: 2020-10-29

Brief Summary

This was a study to investigate the potential clinical benefit of trilaciclib (G1T28) in preserving the bone marrow and the immune system, and enhancing antitumor efficacy when administered with carboplatin, etoposide, and atezolizumab (E/P/A) therapy in first line treatment for patients with newly diagnosed extensive-stage SCLC.

The study was a randomized, double-blinded, placebo-controlled design. Approximately, 100 patients were randomized to trilaciclib + E/P/A or placebo + E/P/A in the study.

Detailed Description

The posted results represent the final results from Study G1T28-05, a Phase 2 study of carboplatin, etoposide, and atezolizumab with or without trilaciclib (G1T28) in patients with untreated extensive-stage small cell lung cancer (SCLC).

The final myelopreservation efficacy results are from database lock 1 (data cut-off [DCO] 17 Aug 2018). The final anti-tumor efficacy data (BOR, DOR, PFS) are from a second database lock 2 (DCO 28 June 2019) that occurred to support the trilaciclib New Drug Application (NDA). Final overall survival and safety data are reported from the final study database lock (DCO 11 Dec 2020, last patient last visit date of 29 October 2020).

Please note the last patient last visit date description above which is recorded as the study completion date. Following the last patient last visit, the final database lock occurred a few weeks later which accounts for the discrepancy between the study completion date and the reported assessment time frames.

Conditions

Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

trilaciclib+etoposide/carboplatin/atezolizumab

Induction: Patients received trilaciclib 240 mg/m² administered intravenously (IV) once daily prior to E/P/A on Days 1, 2 and 3 of each 21-day E/P/A therapy cycle (up to 4 cycles in total). Etoposide 100 mg/m² was administered IV daily on Days 1, 2, and 3 of each 21-day cycle. Carboplatin was administered on Day 1 of each 21-day cycle using the Calvert formula with a target area under the concentration-time curve (AUC) = 5 milligrams per milliliter per minute (mg/mL/min) to calculate the dose. Atezolizumab 1200 mg was administered as an IV infusion on Day 1 of each 21-day cycle.

Maintenance: Following the induction phase, patients received maintenance atezolizumab at a dose of 1200 mg on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or discontinuation by the patient or investigator.

Group Type: EXPERIMENTAL

Trilaciclib

Intervention Type: DRUG

Trilaciclib IV

Carboplatin

Intervention Type: DRUG

Carboplatin IV

Etoposide

Intervention Type: DRUG

Etoposide IV

Atezolizumab

Intervention Type: DRUG

Atezolizumab IV

placebo+etoposide/carboplatin/atezolizumab

Induction: Patients received placebo administered IV once daily prior to E/P/A on Days 1, 2 and 3 of each 21-day E/P/A therapy cycle (up to 4 cycles in total). Etoposide 100 mg/m² was administered IV daily on Days 1, 2, and 3 of each 21-day cycle. Carboplatin was be administered on Day 1 of each 21-day cycle using the Calvert formula with a target AUC = 5 mg/mL/min to calculate the dose. Atezolizumab 1200 mg was administered as an IV infusion on Day 1 of each 21-day cycle.

Maintenance: Following the induction phase, patients received maintenance atezolizumab at a dose of 1200 mg on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or discontinuation by the patient or investigator.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Placebo IV

Carboplatin

Intervention Type: DRUG

Carboplatin IV

Etoposide

Intervention Type: DRUG

Etoposide IV

Atezolizumab

Intervention Type: DRUG

Atezolizumab IV

Interventions

Trilaciclib

Trilaciclib IV

Intervention Type: DRUG

Placebo

Placebo IV

Intervention Type: DRUG

Carboplatin

Carboplatin IV

Intervention Type: DRUG

Etoposide

Etoposide IV

Intervention Type: DRUG

Atezolizumab

Atezolizumab IV

Intervention Type: DRUG

Other Intervention Names

G1T28; Paraplatin; VP-16; Tecentriq

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
• Extensive-stage SCLC
• At least 1 target lesion that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
• Adequate organ function
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
• Predicted life expectancy of ≥3 months
• Able to understand and sign an informed consent

Exclusion Criteria

• Limited-stage SCLC
• Prior chemotherapy for limited or extensive-stage SCLC
• Prior treatment with immunotherapies including but not limited to cluster of differentiation 137 agonists or immune checkpoint blockade therapies (such as anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1(PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapeutic antibodies).
• Presence of symptomatic brain metastases requiring immediate treatment with radiation therapy or steroids.
• Malignancies other than SCLC within 3 years prior to randomization, with the exception of those with negligible risk of metastasis or death treated with expected curative outcome
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• Active, known, suspected autoimmune disease requiring systemic treatment in the past 2 years
• Uncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failure
• Known history of stroke or cerebrovascular accident within 6 months prior to enrollment
• Serious active infection at the time of enrollment
• Psychiatric illness/social situations that would limit study compliance
• Other uncontrolled serious chronic disease or conditions that in the investigator's opinion could affect compliance or follow-up in the protocol
• Known human immunodeficiency virus, known active hepatitis B, or hepatitis C
• Radiotherapy to any site or radiotherapy within 2 weeks prior to enrollment
• Receipt of any investigational medication within 4 weeks prior to enrollment
• Administration of attenuated vaccine within 4 weeks before enrollment or anticipation that such a live attenuated vaccine will be required during the study
• Influenza vaccination should be given during influenza season only (approx. Oct to March). Patients must not receive live, attenuated influenza vaccine (eg, FluMist) within 4 weeks prior to enrollment at any time during the study, and at least 5 months after the last dose of atezolizumab.
• Patients with a condition requiring systemic treatment with either corticosteroids ( > 10 mg daily prednisone equivalents) or other immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 14 days of study drug administration. Inhaled or topical steroids ad adrenal replacement dosed > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Hypersensitivity to any of the components of the formulation of etoposide or etoposide phosphate
• Hypersensitivity to carboplatin or other platinum-containing compounds or to mannitol
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• Legal incapacity or limited legal capacity
• Pregnant or lactating women

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roche-Genentech

INDUSTRY

Sponsor Role: collaborator

G1 Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Contact

Role: STUDY_DIRECTOR

G1 Therapeutics, Inc.

Locations

Beverly Hills Cancer Center

Beverly Hills, California, United States

St. Jude Heritage Healthcare

Fullerton, California, United States

Loma Linda University

Loma Linda, California, United States

UCLA Medical Center - Santa Monica Hematology And Oncology

Santa Monica, California, United States

Redwood Regional Medical Group (RRMG) - Fountain Grove

Santa Rosa, California, United States

Singing River Health System

Whittier, California, United States

Piedmont Cancer Institute

Atlanta, Georgia, United States

Northside Hospital - Georgia Cancer Specialists

Atlanta, Georgia, United States

Joliet Oncology-Hematology Associates

Joliet, Illinois, United States

Horizon Oncology Center

Lafayette, Indiana, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

St. Louis Cancer Care, LLP, North County

Bridgeton, Missouri, United States

The Alvin J. Siteman Cancer Center - Center for Advanced Med

St Louis, Missouri, United States

Summit Medical Group, P.A.

Morristown, New Jersey, United States

Northern Westchester Hospital

Mount Kisco, New York, United States

Trinity Health - Trinity CancerCare Center

Minot, North Dakota, United States

Oklahoma University - Peggy and Charles Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Gibbs Cancer Center

Spartanburg, South Carolina, United States

Valley Cancer Associates

Harlingen, Texas, United States

Millennium Oncology

Houston, Texas, United States

Virginia Cancer Specialists

Arlington, Virginia, United States

Blue Ridge Cancer Care

Blacksburg, Virginia, United States

Fort Belvoir Community Hospital

Fort Belvoir, Virginia, United States

Complex Oncology Center - Burgas

Burgas, , Bulgaria

Multiprofile Hospital for Active Treatment "Serdika", Sofia

Sofia, , Bulgaria

Multiprofile Hospital for Active Treatment "Serdika"

Sofia, , Bulgaria

East Tallinn Central Hospital Ltd., Clinic of Internal Medicine, Center for Oncology

Tallinn, , Estonia

CHU Caen De La Côte De Nacre

Caen, , France

Centre Oscar Lambret

Lille, , France

Daugavpils Regional Hospital, Department of Oncology

Daugavpils, , Latvia

Pauls Stradiņš Clinical University Hospital, Oncology Clinic

Riga, , Latvia

Hospital Universitario Son Espases

Palma, Balearic Islands, Spain

Hospital Teresa Herrera

A Coruña, La Coruña, Spain

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, Spain

Hospital Clínico

San Carlos, Madrid, Spain

H.U. Quirón Dexeus, Hospital Universitario

Barcelona, , Spain

Hospital Clinic de Barcelona- Servicio de Oncología Médica

Barcelona, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Hospital 12 de Octubre

Madrid, , Spain

H. Donostia, Hospital Donostia- Servicio de Oncología

San Sebastián, , Spain

Hospital Universitario Ntra. Sra. de Valme

Seville, , Spain

Hospital Arnau de Vilanova

Valencia, , Spain

Chernivtsi Regional Clinical Oncology Center

Chernivtsi, , Ukraine

Dnipropetrovsk City Multispecialty Clinical Hospital #4

Dnipro, , Ukraine

Lviv State Regional Treatment and Diagnostics Oncology Center

Lviv, , Ukraine

Countries

United States; Bulgaria; Estonia; France; Latvia; Spain; Ukraine

References

Daniel D, Kuchava V, Bondarenko I, Ivashchuk O, Reddy S, Jaal J, Kudaba I, Hart L, Matitashvili A, Pritchett Y, Morris SR, Sorrentino JA, Antal JM, Goldschmidt J. Trilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive-stage small cell lung cancer: A multicentre, randomised, double-blind, placebo-controlled Phase II trial. Int J Cancer. 2021 May 15;148(10):2557-2570. doi: 10.1002/ijc.33453. Epub 2021 Jan 12.

Reference Type: BACKGROUND

PMID: 33348420 (View on PubMed)

Weiss J, Goldschmidt J, Andric Z, Dragnev KH, Gwaltney C, Skaltsa K, Pritchett Y, Antal JM, Morris SR, Daniel D. Effects of Trilaciclib on Chemotherapy-Induced Myelosuppression and Patient-Reported Outcomes in Patients with Extensive-Stage Small Cell Lung Cancer: Pooled Results from Three Phase II Randomized, Double-Blind, Placebo-Controlled Studies. Clin Lung Cancer. 2021 Sep;22(5):449-460. doi: 10.1016/j.cllc.2021.03.010. Epub 2021 Mar 26.

Reference Type: BACKGROUND

PMID: 33895103 (View on PubMed)

Abraham I, Onyekwere U, Deniz B, Moran D, Chioda M, MacDonald K, Huang H. Trilaciclib and the economic value of multilineage myeloprotection from chemotherapy-induced myelosuppression among patients with extensive-stage small cell lung cancer treated with first-line chemotherapy. J Med Econ. 2021 Nov;24(sup1):71-83. doi: 10.1080/13696998.2021.2014163.

Reference Type: DERIVED

PMID: 34873975 (View on PubMed)

Zeng R, Liu F, Fang C, Yang J, Luo L, Yue P, Gao B, Dong Y, Xiang Y. PIV and PILE Score at Baseline Predict Clinical Outcome of Anti-PD-1/PD-L1 Inhibitor Combined With Chemotherapy in Extensive-Stage Small Cell Lung Cancer Patients. Front Immunol. 2021 Oct 29;12:724443. doi: 10.3389/fimmu.2021.724443. eCollection 2021.

Reference Type: DERIVED

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Hussein M, Maglakelidze M, Richards DA, Sabatini M, Gersten TA, Lerro K, Sinielnikov I, Spira A, Pritchett Y, Antal JM, Malik R, Beck JT. Myeloprotective Effects of Trilaciclib Among Patients with Small Cell Lung Cancer at Increased Risk of Chemotherapy-Induced Myelosuppression: Pooled Results from Three Phase 2, Randomized, Double-Blind, Placebo-Controlled Studies. Cancer Manag Res. 2021 Aug 9;13:6207-6218. doi: 10.2147/CMAR.S313045. eCollection 2021.

Reference Type: DERIVED

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Ferrarotto R, Anderson I, Medgyasszay B, Garcia-Campelo MR, Edenfield W, Feinstein TM, Johnson JM, Kalmadi S, Lammers PE, Sanchez-Hernandez A, Pritchett Y, Morris SR, Malik RK, Csoszi T. Trilaciclib prior to chemotherapy reduces the usage of supportive care interventions for chemotherapy-induced myelosuppression in patients with small cell lung cancer: Pooled analysis of three randomized phase 2 trials. Cancer Med. 2021 Sep;10(17):5748-5756. doi: 10.1002/cam4.4089. Epub 2021 Aug 18.

Reference Type: DERIVED

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Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan: Region 2

View Document

Other Identifiers

2017-000358-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

G1T28-05

Identifier Type: -

Identifier Source: org_study_id