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

NCT03041311 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: G1T28-052017-000358-20
• Study Type: interventional
• Target: 107
• Locations: 6 countries
• Sites: 44

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.

Conditions

Small Cell Lung Cancer

Keywords

Small Cell Lung Cancer; CDK4/6 Inhibitor; Immune Checkpoint Inhibitor

Outcome Measures

Primary Outcomes (2)

• Duration of Severe (Grade 4) Neutropenia in Cycle 1

  Duration of severe neutropenia (DSN; days) was defined as the number of days from the date of the first absolute neutrophil count (ANC) value of \<0.5 × 10⁹/L observed between start of cycle and end of cycle to the date of the first ANC value ≥0.5 × 10⁹/L that met the following criteria: (1) occurred after the ANC value of \<0.5 × 10⁹/L and (2) no other ANC values \<0.5 × 10⁹/L occurred between this day and end of cycle. DSN was set to 0 for patients who did not experience severe neutropenia in a cycle, including those that were randomized and not treated. Data from unscheduled visits and the actual assessment date (rather than visit date) were included in the derivation.

  Evaluated for Cycle 1 of the Induction Period (i.e., from randomization to the end of Cycle 1, each cycle = 21 days).

• Number of Participants With at Least 1 Occurrence of Severe (Grade 4) Neutropenia

  The occurrence of severe (Grade 4) neutropenia (SN) was a binary variable. If a patient had at least 1 absolute neutrophil count value \<0.5 × 10\^9/L during the Induction Period, the patient was assigned as Yes to the occurrence of SN; otherwise, it was No.

  Induction Period. From date of randomization, 21 day treatment cycles up to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days.

Secondary Outcomes (25)

• All-Cause Dose Reductions

  Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days.

• Number of Participants With at Least 1 Occurrence of RBC Transfusion on/After Week 5 (Proportion of Patients)

  Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 374 days.

• Occurrence of Granulocyte Colony-Stimulating Factor (G-CSF) Administration (Proportion of Patients)

  Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days.

• Overall Survival (OS)

  From date of randomization to date of death due to any cause, assessed up to a maximum of 38.1 months.

• Major Adverse Hematologic Events (MAHE) (Composite Endpoint)

  Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days.

Study Arms (2)

trilaciclib+etoposide/carboplatin/atezolizumab

EXPERIMENTAL

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.

Drug: Trilaciclib; Drug: Carboplatin; Drug: Etoposide; Drug: Atezolizumab

placebo+etoposide/carboplatin/atezolizumab

EXPERIMENTAL

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.

Drug: Placebo; Drug: Carboplatin; Drug: Etoposide; Drug: Atezolizumab

Interventions

Trilaciclib DRUG

Trilaciclib IV

Also known as: G1T28

trilaciclib+etoposide/carboplatin/atezolizumab

Placebo DRUG

Placebo IV

placebo+etoposide/carboplatin/atezolizumab

Carboplatin DRUG

Carboplatin IV

Also known as: Paraplatin

placebo+etoposide/carboplatin/atezolizumab; trilaciclib+etoposide/carboplatin/atezolizumab

Etoposide DRUG

Etoposide IV

Also known as: VP-16

placebo+etoposide/carboplatin/atezolizumab; trilaciclib+etoposide/carboplatin/atezolizumab

Atezolizumab DRUG

Atezolizumab IV

Also known as: Tecentriq

placebo+etoposide/carboplatin/atezolizumab; trilaciclib+etoposide/carboplatin/atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• G1 Therapeutics, Inc.: lead
• Roche-Genentech: collaborator

Study Sites (45)

Beverly Hills Cancer Center

Beverly Hills, California, 90211, United States

Location

St. Jude Heritage Healthcare

Fullerton, California, 92835, United States

Location

Loma Linda University

Loma Linda, California, 92350, United States

Location

UCLA Medical Center - Santa Monica Hematology And Oncology

Santa Monica, California, 90404, United States

Location

Redwood Regional Medical Group (RRMG) - Fountain Grove

Santa Rosa, California, 95403, United States

Location

Singing River Health System

Whittier, California, 90603, United States

Location

Piedmont Cancer Institute

Atlanta, Georgia, 30318, United States

Location

Northside Hospital - Georgia Cancer Specialists

Atlanta, Georgia, 30341, United States

Location

Joliet Oncology-Hematology Associates

Joliet, Illinois, 60435, United States

Location

Horizon Oncology Center

Lafayette, Indiana, 47905, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

St. Louis Cancer Care, LLP, North County

Bridgeton, Missouri, 63044, United States

Location

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

St Louis, Missouri, 63110-1094, United States

Location

Summit Medical Group, P.A.

Morristown, New Jersey, 07962, United States

Location

Northern Westchester Hospital

Mount Kisco, New York, 10549, United States

Location

Trinity Health - Trinity CancerCare Center

Minot, North Dakota, 58701, United States

Location

Oklahoma University - Peggy and Charles Stephenson Cancer Center

Oklahoma City, Oklahoma, 73117, United States

Location

Gibbs Cancer Center

Spartanburg, South Carolina, 29303, United States

Location

Valley Cancer Associates

Harlingen, Texas, 78550, United States

Location

Millennium Oncology

Houston, Texas, 77090, United States

Location

Virginia Cancer Specialists

Arlington, Virginia, 22031, United States

Location

Blue Ridge Cancer Care

Blacksburg, Virginia, 24060, United States

Location

Fort Belvoir Community Hospital

Fort Belvoir, Virginia, 22060, United States

Location

Complex Oncology Center - Burgas

Burgas, 8000, Bulgaria

Location

Multiprofile Hospital for Active Treatment "Serdika", Sofia

Sofia, 1303, Bulgaria

Location

Multiprofile Hospital for Active Treatment "Serdika"

Sofia, 1303, Bulgaria

Location

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

Tallinn, 11312, Estonia

Location

CHU Caen De La Côte De Nacre

Caen, 14033, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Daugavpils Regional Hospital, Department of Oncology

Daugavpils, LV-5417, Latvia

Location

Pauls Stradiņš Clinical University Hospital, Oncology Clinic

Riga, LV-1002, Latvia

Location

Hospital Universitario Son Espases

Palma, Balearic Islands, 07120, Spain

Location

Hospital Teresa Herrera

A Coruña, La Coruña, 15006, Spain

Location

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, 28222, Spain

Location

Hospital Clínico

San Carlos, Madrid, 28040, Spain

Location

H.U. Quirón Dexeus, Hospital Universitario

Barcelona, 08028, Spain

Location

Hospital Clinic de Barcelona- Servicio de Oncología Médica

Barcelona, 08036, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital 12 de Octubre

Madrid, 28041, Spain

Location

H. Donostia, Hospital Donostia- Servicio de Oncología

San Sebastián, 20014, Spain

Location

Hospital Universitario Ntra. Sra. de Valme

Seville, 41014, Spain

Location

Hospital Arnau de Vilanova

Valencia, 46015, Spain

Location

Chernivtsi Regional Clinical Oncology Center

Chernivtsi, 58013, Ukraine

Location

Dnipropetrovsk City Multispecialty Clinical Hospital #4

Dnipro, 49102, Ukraine

Location

Lviv State Regional Treatment and Diagnostics Oncology Center

Lviv, 79031, Ukraine

Location

Related Publications (6)

• 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.

  PMID: 33348420 BACKGROUND

• 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.

  PMID: 33895103 BACKGROUND

• 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.

  PMID: 34873975 DERIVED

• 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.

  PMID: 34777341 DERIVED

• 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.

  PMID: 34408488 DERIVED

• 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.

  PMID: 34405547 DERIVED

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

trilaciclib; Carboplatin; Etoposide; atezolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Limitations and Caveats

Limitation of the trial is small numbers of subjects, since it is a Phase 2 clinical trial. Small sample size may have reduced the ability to observe statistically significant treatment effects on secondary myelopreservation measures (i.e. occurrence of FN AEs, infections and antibiotics usage).

Results Point of Contact

• Title: Clinical Trial Info.
• Organization: G1 Therapeutics, Inc.

clinicalinfo@g1therapeutics.com

919-213-9835

Study Officials

• Clinical Contact

  G1 Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2017
• First Posted: February 2, 2017
• Study Start: June 29, 2017
• Primary Completion: August 17, 2018
• Study Completion: October 29, 2020
• Last Updated: September 25, 2025
• Results First Posted: May 6, 2022

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

UA (3); US (23); BU (3); FR (2); LA (2); ES (11)