Phase 2 Study of Carboplatin, Etoposide, and Atezolizumab With or Without Trilaciclib in Patients With Untreated Extensive-Stage Small Cell Lung Cancer (SCLC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 107
- 试验地点
- 45
- 主要终点
- Duration of Severe (Grade 4) Neutropenia in Cycle 1
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Trilaciclib (Drug)
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.
干预措施: Carboplatin (Drug)
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.
干预措施: Etoposide (Drug)
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.
干预措施: Atezolizumab (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Carboplatin (Drug)
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.
干预措施: Etoposide (Drug)
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.
干预措施: Atezolizumab (Drug)
结局指标
主要结局
Duration of Severe (Grade 4) Neutropenia in Cycle 1
时间窗: Evaluated for Cycle 1 of the Induction Period (i.e., from randomization to the end of Cycle 1, each cycle = 21 days).
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.
Number of Participants With at Least 1 Occurrence of Severe (Grade 4) Neutropenia
时间窗: 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.
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.
次要结局
- Duration of Objective Response (Complete Response or Partial Response)(From date of randomization, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 724 days.)
- Number of Participants With at Least 1 Occurrence of Erythropoiesis Stimulating Agent (ESA) Administration(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 Pulmonary Infection Serious Adverse Events (SAEs)(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.)
- 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.)
- 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.)
- Number of Participants With at Least 1 Occurrence of Febrile Neutropenia(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.)
- 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.)
- Best Overall Response(From date of randomization, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 724 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.)
- Progression-Free Survival(From date of randomization, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 724 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.)
- Number of Participants With at Least 1 Occurrence of Grade 3 or 4 Hematologic Laboratory Abnormalities(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 Infection Serious Adverse Events (SAEs)(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 IV Antibiotic Uses(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 Platelet Transfusion(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 Any Cycle Delays and the Number of Cycles Delayed (Induction Period)(Induction Period. From date of first dose, 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 Any Cycle Delays and the Number of Cycles Delayed (Maintenance Period)(Maintenance Period. From date of first maintenance dose, 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 1160 days.)
- Number of Participants With Any Dose Interruptions [for Each Study Drug: Trilaciclib/Placebo, Carboplatin and Etoposide] (Induction Period)(Induction Period. From date of first dose, 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 Any Interrupted Doses of Atezolizumab (Overall Treatment Period)(From date of first dose, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 1162 days.)
- Duration of Study Drug Exposure (Induction Period and Maintenance Period)(From date of first dose, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 1162 days.)
- Number of Cycles Completed (Induction Period and Maintenance Period)(From date of first dose, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 49 cycles.)
- Relative Dose Intensity of Trilaciclib/Placebo, Carboplatin, Etoposide, Atezolizumab (Induction Period) and Atezolizumab (Maintenance Period)(From date of first dose, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 724 days.)
- Number of Participants With Any Missed Doses [for Each Study Drug: Trilaciclib/Placebo, Carboplatin and Etoposide] (Induction Period)(Induction Period. From date of first dose, 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 Any Missed Doses of Atezolizumab (Overall Treatment Period)(From date of first dose, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 1162 days.)
- Number of Participants With Any Dose Reductions of Carboplatin and Etoposide (Induction Period)(Induction Period. From date of first dose, 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.)