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

G1 Therapeutics

Status and phase: Completed; Phase 2

Conditions: Small Cell Lung Cancer

Treatments: Drug: Carboplatin; Drug: Etoposide; Drug: Atezolizumab; Drug: Trilaciclib; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03041311

G1T28-05

2017-000358-20 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 107 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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107 participants in 2 patient groups

trilaciclib+etoposide/carboplatin/atezolizumab

Experimental group

Description:

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.

Treatment:

Drug: Atezolizumab

Drug: Trilaciclib

Drug: Etoposide

Drug: Carboplatin

placebo+etoposide/carboplatin/atezolizumab

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Atezolizumab

Drug: Etoposide

Drug: Carboplatin