Carboplatin, Etoposide, and Atezolizumab With or Without Trilaciclib (G1T28), a CDK4/6 Inhibitor, in Extensive-Stage SCLC
Condition: Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Intervention: Trilaciclib; Placebo; Carboplatin; Etoposide; Atezolizumab
Intervention description: Trilaciclib IV; Placebo IV; Carboplatin IV; Etoposide IV; Atezolizumab IV
Intervention MeSH terms: Carboplatin; Etoposide; Atezolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 107.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Small Cell Lung Cancer; CDK4/6 Inhibitor; Immune Checkpoint Inhibitor

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.
    

Eligibility 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