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

Primary Purpose

Small Cell Lung Cancer

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Trilaciclib

Placebo

Carboplatin

Etoposide

Atezolizumab

About this trial

This is an interventional treatment trial for Small Cell Lung Cancer focused on measuring Small Cell Lung Cancer, CDK4/6 Inhibitor, Immune Checkpoint Inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Beverly Hills Cancer Center
St. Jude Heritage Healthcare
Loma Linda University
UCLA Medical Center - Santa Monica Hematology And Oncology
Redwood Regional Medical Group (RRMG) - Fountain Grove
Singing River Health System
Piedmont Cancer Institute
Northside Hospital - Georgia Cancer Specialists
Joliet Oncology-Hematology Associates
Horizon Oncology Center
Ochsner Clinic Foundation
St. Louis Cancer Care, LLP, North County
The Alvin J. Siteman Cancer Center - Center for Advanced Med
Summit Medical Group, P.A.
Northern Westchester Hospital
Trinity Health - Trinity CancerCare Center
Oklahoma University - Peggy and Charles Stephenson Cancer Center
Gibbs Cancer Center
Valley Cancer Associates
Millennium Oncology
Virginia Cancer Specialists
Blue Ridge Cancer Care
Fort Belvoir Community Hospital
Complex Oncology Center - Burgas
Multiprofile Hospital for Active Treatment "Serdika", Sofia
Multiprofile Hospital for Active Treatment "Serdika"
East Tallinn Central Hospital Ltd., Clinic of Internal Medicine, Center for Oncology
CHU Caen De La Côte De Nacre
Centre Oscar Lambret
Daugavpils Regional Hospital, Department of Oncology
Pauls Stradiņš Clinical University Hospital, Oncology Clinic
Hospital Universitario Son Espases
Hospital Teresa Herrera
Hospital Universitario Puerta de Hierro Majadahonda
Hospital Clínico
H.U. Quirón Dexeus, Hospital Universitario
Hospital Clinic de Barcelona- Servicio de Oncología Médica
Hospital Universitario Ramón y Cajal
Hospital 12 de Octubre
H. Donostia, Hospital Donostia- Servicio de Oncología
Hospital Universitario Ntra. Sra. de Valme
Hospital Arnau de Vilanova
Chernivtsi Regional Clinical Oncology Center
Dnipropetrovsk City Multispecialty Clinical Hospital #4
Lviv State Regional Treatment and Diagnostics Oncology Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

trilaciclib+etoposide/carboplatin/atezolizumab

placebo+etoposide/carboplatin/atezolizumab

Arm 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.

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.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

All-Cause Dose Reductions

Dose reductions are not permitted for trilaciclib or atezolizumab. Dose reductions for E/P are derived from changes in the protocol-specified dose on the dosing page and correspond to the reductions for toxicity specified in the protocol. No more than 2 dose reductions of E/P in total were allowed for any patient. Simultaneous reduction in the doses of etoposide and carboplatin were counted as 1 dose reduction.

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

For this endpoint, the occurrence during the Induction Period was defined as a binary variable (Yes or No); Yes, if total number of events ≥1 was observed, No for other scenarios. If a patient did not have an event, a value of 0 was assigned to that patient. Each red blood cell transfusion with a unique start date on/after Week 5 on study during the Induction was defined as a separate event.

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

For this endpoint, the occurrence during the Induction Period was defined as a binary variable (Yes or No); Yes, if total number of events ≥1 was observed, No for other scenarios. If a patient did not have an event, a value of 0 was assigned to that patient. Any G-CSF administration in a cycle during the Induction Period was defined as a separate event. A patient with at least 1 cycle with G-CSF administration during an induction cycle or the Induction Period was considered to have occurrence of G-CSF administration.

Overall Survival (OS)

Overall survival was calculated as the time (months) from date of randomization to the date of death due to any cause. Patients who did not die during the study were censored at the date last known to be alive. Patients lacking data beyond the date of randomization had their survival time censored at date of randomization. Overall survival was not censored if a patient received other anti-tumor treatments after the study drugs. Overall survival was calculated using the Kaplan-Meier method.

Major Adverse Hematologic Events (MAHE) (Composite Endpoint)

The composite endpoint "major adverse hematologic events" (MAHE) included the following aspects of myelosuppression: All-cause hospitalizations - Each recorded preferred term (PT) with a unique start date was counted as an event. All-cause dose reductions - Dose reductions were permitted for E/P but not for trilaciclib or atezolizumab. No more than 2 dose reductions were allowed. Each dose reduction was counted as a separate event. Febrile neutropenia-Each febrile neutropenia event with a unique start date during the Induction Period was defined as a separate event. Prolonged severe neutropenia (SN)-Each cycle with a severe neutropenia duration greater than 5 days was counted as an event, with the date of the first Grade 4 laboratory value defined as the start date for the time-to-first event analysis. Red blood cell (RBC) transfusion on/after Week 5-Each RBC transfusion with a unique start date on/after Week 5 on study during the Induction Period was defined as a separate event.

Best Overall Response

For all patients, the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) tumor response data were used to determine each patient's visit response (TPR = time point response). Per RECIST v1.1 for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameters of target lesions; Progressive Disease (PD), >=20% increase in the sum of the longest diameter of target lesions, Stable Disease, neither sufficient shrinkage or increase to quality for PR or PD. Objective Response Rate (ORR) = CR + PR. The TPR at each visit was determined in 2 ways: (1) derived programmatically at the time of analysis using the information from target lesions, non-target lesions, and new lesions based on data collected through eCRF; and (2) judged by the investigator as collected in the eCRF. Results shown here are from the programmatically derived assessments.

Duration of Objective Response (Complete Response or Partial Response)

Duration of Response (DOR) is the time between first response by RECIST Version 1.1 of CR or PR and the first date that progressive disease is documented by RECIST Version 1.1, or death. Patients who do not experience PD or death will be censored at the last tumor assessment date. Only those patients with confirmed responses will be included in this analysis.

Progression-Free Survival

Progression-free survival (PFS) was defined as the time (number of months) from date of randomization until date of documented radiologic disease progression per RECIST v1.1 or death due to any cause, whichever came first.

Number of Participants With at Least 1 Occurrence of Febrile Neutropenia

The criterion for identifying febrile neutropenia was if the preferred term for an adverse event was "FEBRILE NEUTROPENIA." Any occurrence of a febrile neutropenia event during the induction treatment period is defined as a binary variable (Yes or No); Yes if total number of febrile neutropenia events ≥ 1 is observed, No for other scenarios. Each febrile neutropenia event with a unique start date during the induction treatment period was defined as a separate event.

Number of Participants With at Least 1 Occurrence of Grade 3 or 4 Hematologic Laboratory Abnormalities

The occurrence of Grade 3 and 4 hematologic toxicities was a binary endpoint. If a patient had at least 1 cycle with at least 1 Grade 3 or 4 hematologic toxicities during the Induction Period, the patient was assigned as "Yes" to the occurrence of Grade 3 and 4 hematologic toxicities; otherwise, it was "No". If a patient did not have an event, the value of 0 was assigned to that patient.

Number of Participants With at Least 1 Occurrence of Erythropoiesis Stimulating Agent (ESA) Administration

Any ESA administration in a cycle during the Induction Period was defined as a separate event. A patient with at least 1 cycle with ESA administration during an induction cycle or the Induction Period was considered to have occurrence of ESA administration. The criterion to select proper records was as follows: If the chemical subgroup from WHO-DD Version September 2017 (ie TEXT4 for CODE4) takes the value "OTHER ANTIANEMIC PREPARATIONS," the medication was classified as ESAs.

Number of Participants With at Least 1 Occurrence of Platelet Transfusion

Any occurrence of a platelet transfusion during the induction treatment period was defined as a binary variable (Yes or No); Yes if total number of febrile neutropenia events ≥ 1 is observed, No for other scenarios. If the patient did not have an event, the value of 0 was assigned to that patient. Each platelet transfusion event with a unique start date during the induction treatment period was defined as a separate event.

Number of Participants With at Least 1 Occurrence of Infection Serious Adverse Events (SAEs)

Any occurrence of an infection SAE during the induction treatment period was defined as a binary variable (Yes or No); Yes if total number of febrile neutropenia events ≥ 1 is observed, No for other scenarios. If the patient did not have an event, the value of 0 was assigned to that patient. The criterion for identifying the proper infection SAE records was as follows: if the system organ class (SOC) from Medical Dictionary for Regulatory Activities (MedDRA) Version 20.1 takes value "INFECTIONS AND INFESTATIONS," and the AE was a serious event.

Number of Participants With at Least 1 Occurrence of Pulmonary Infection Serious Adverse Events (SAEs)

Any occurrence of a pulmonary SAE during the induction treatment period was defined as a binary variable (Yes or No); Yes if total number of febrile neutropenia events ≥ 1 is observed, No for other scenarios. If the patient did not have an event, the value of 0 was assigned to that patient. Each pulmonary infection SAE with a unique start date during the induction treatment period was defined as separate event. The criterion for identifying the proper pulmonary infection SAE records was as follows: The SOC from MedDRA Version 20.1 took the value "INFECTIONS AND INFESTATIONS," the adverse event was a serious event, and the PT took values from the following list of PTs under the category of pulmonary infection adverse events: bronchiolitis, bronchitis, infectious pleural effusion, influenza, pneumonia, pneumonia bacterial, respiratory tract infection, upper respiratory tract infection, and viral upper respiratory tract infection.

Number of Participants With at Least 1 Occurrence of IV Antibiotic Uses

Occurrence of an IV antibiotics administration during the induction treatment period is defined as a binary variable (Yes or No); Yes if total number of IV antibiotics administration ≥ 1 is observed, No for other scenarios. Each IV antibiotic with a unique start date during the induction treatment period will be defined as a separate event. The criteria for identifying an IV antibiotic administration event was (1) if the therapeutic subgroup from WHO-DD Version September 2017 (ie, TEXT2 for CODE2) takes the value "ANTIBACTERIALS FOR SYSTEMIC USE," and (2) the route of medication was "intravenous" or the route was "other" with the detailed specification as "IVPB."

Duration of Study Drug Exposure (Induction Period and Maintenance Period)

Induction period duration of exposure (days) = Day 1 of last induction cycle - Cycle 1 Day 1 of induction phase + 21. Maintenance period duration of exposure (days) = Day 1 of the last maintenance cycle -Cycle 1 Day 1 of maintenance phase + 21.

Number of Cycles Completed (Induction Period and Maintenance Period)

Patients were considered to have started a cycle if they have received at least one dose of any study drug (carboplatin, etoposide, atezolizumab or trilaciclib).

Relative Dose Intensity of Trilaciclib/Placebo, Carboplatin, Etoposide, Atezolizumab (Induction Period) and Atezolizumab (Maintenance Period)

Relative dose intensity is defined as 100% times the actual dose intensity divided by the planned dose intensity. The planned dose intensity is defined as the cumulative planned dose through the study divided by (number of cycles * 3 weeks)

Number of Participants With Any Cycle Delays and the Number of Cycles Delayed (Induction Period)

After Cycle 1, patients need to meet pre-specified laboratory parameter criteria before initiating Cycle 2 and each subsequent cycle of chemotherapy. A "Cycle Day Status" page asks if the cycle was delayed. If the start of the current cycle was delayed (the site answers "Yes"), this will be counted as a delay. Cycle delays could occur for management of toxicity (hematologic or non-hematologic) or for administrative/logistic reasons. The reason for each cycle delay was captured in the eCRF if it was related to AEs. Reasons other than AEs were not captured.

Number of Participants With Any Cycle Delays and the Number of Cycles Delayed (Maintenance Period)

Number of Participants With Any Missed Doses [for Each Study Drug: Trilaciclib/Placebo, Carboplatin and Etoposide] (Induction Period)

Missed doses are identified on the dosing page of each study drug based on the question "Was the dose given?". The missed dose information will be obtained for each study drug. For a study drug, if the last record of response to question "Was the dose given?" is No, it will not be considered as a missed dose but instead considered to be end of treatment if both criteria below are met: (1) No other study drugs are given on the same day, and (2) No study drugs are given subsequently.

Number of Participants With Any Missed Doses of Atezolizumab (Overall Treatment Period)

Number of Participants With Any Dose Interruptions [for Each Study Drug: Trilaciclib/Placebo, Carboplatin and Etoposide] (Induction Period)

Dose interruptions were defined as interruption of infusion, regardless of whether the study drug was continued after the interruption.

Number of Participants With Any Interrupted Doses of Atezolizumab (Overall Treatment Period)

Dose interruptions were defined as interruption of infusion, regardless of whether the study drug was continued after the interruption.

Number of Participants With Any Dose Reductions of Carboplatin and Etoposide (Induction Period)

No dose reductions were allowed for trilaciclib or atezolizumab during the study.

Full Information

NCT ID

NCT03041311

First Posted

February 1, 2017

Last Updated

April 8, 2022

Sponsor

G1 Therapeutics, Inc.

Collaborators

Roche-Genentech

1. Study Identification

Unique Protocol Identification Number

NCT03041311

Brief Title

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

Official Title

Phase 2 Study of Carboplatin, Etoposide, and Atezolizumab With or Without Trilaciclib in Patients With Untreated Extensive-Stage Small Cell Lung Cancer (SCLC)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Terminated

Why Stopped

Primary Analysis and survival follow up completed per protocol. Not stopped due to safety concerns.

Study Start Date

June 29, 2017 (Actual)

Primary Completion Date

August 17, 2018 (Actual)

Study Completion Date

October 29, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

G1 Therapeutics, Inc.

Collaborators

Roche-Genentech

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Small Cell Lung Cancer

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

107 (Actual)

8. Arms, Groups, and Interventions

Arm Title

trilaciclib+etoposide/carboplatin/atezolizumab

Arm Type

Experimental

Arm Description

Arm Title

placebo+etoposide/carboplatin/atezolizumab

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Trilaciclib

Other Intervention Name(s)

G1T28

Intervention Description

Trilaciclib IV

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo IV

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Other Intervention Name(s)

Paraplatin

Intervention Description

Carboplatin IV

Intervention Type

Drug

Intervention Name(s)

Etoposide

Other Intervention Name(s)

VP-16

Intervention Description

Etoposide IV

Intervention Type

Drug

Intervention Name(s)

Atezolizumab

Other Intervention Name(s)

Tecentriq

Intervention Description

Atezolizumab IV

Primary Outcome Measure Information:

Title

Duration of Severe (Grade 4) Neutropenia in Cycle 1

Description

Time Frame

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

Title

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

Description

Time Frame

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 Outcome Measure Information:

Title

All-Cause Dose Reductions

Description

Time Frame

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.

Title

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

Description

Time Frame

Title

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

Description

For this endpoint, the occurrence during the Induction Period was defined as a binary variable (Yes or No); Yes, if total number of events ≥1 was observed, No for other scenarios. If a patient did not have an event, a value of 0 was assigned to that patient. Any G-CSF administration in a cycle during the Induction Period was defined as a separate event. A patient with at least 1 cycle with G-CSF administration during an induction cycle or the Induction Period was considered to have occurrence of G-CSF administration.

Time Frame

Title

Overall Survival (OS)

Description

Time Frame

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

Title

Major Adverse Hematologic Events (MAHE) (Composite Endpoint)

Description

Time Frame

Title

Best Overall Response

Description

Time Frame

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.

Title

Duration of Objective Response (Complete Response or Partial Response)

Description

Time Frame

Title

Progression-Free Survival

Description

Time Frame

Title

Number of Participants With at Least 1 Occurrence of Febrile Neutropenia

Description

Time Frame

Title

Number of Participants With at Least 1 Occurrence of Grade 3 or 4 Hematologic Laboratory Abnormalities

Description

Time Frame

Title

Number of Participants With at Least 1 Occurrence of Erythropoiesis Stimulating Agent (ESA) Administration

Description

Time Frame

Title

Number of Participants With at Least 1 Occurrence of Platelet Transfusion

Description

Time Frame

Title

Number of Participants With at Least 1 Occurrence of Infection Serious Adverse Events (SAEs)

Description

Time Frame

Title

Number of Participants With at Least 1 Occurrence of Pulmonary Infection Serious Adverse Events (SAEs)

Description

Time Frame

Title

Number of Participants With at Least 1 Occurrence of IV Antibiotic Uses

Description

Time Frame

Title

Duration of Study Drug Exposure (Induction Period and Maintenance Period)

Description

Time Frame

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.

Title

Number of Cycles Completed (Induction Period and Maintenance Period)

Description

Patients were considered to have started a cycle if they have received at least one dose of any study drug (carboplatin, etoposide, atezolizumab or trilaciclib).

Time Frame

Title

Relative Dose Intensity of Trilaciclib/Placebo, Carboplatin, Etoposide, Atezolizumab (Induction Period) and Atezolizumab (Maintenance Period)

Description

Time Frame

Title

Number of Participants With Any Cycle Delays and the Number of Cycles Delayed (Induction Period)

Description

Time Frame

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.

Title

Number of Participants With Any Cycle Delays and the Number of Cycles Delayed (Maintenance Period)

Description

Time Frame

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.

Title

Number of Participants With Any Missed Doses [for Each Study Drug: Trilaciclib/Placebo, Carboplatin and Etoposide] (Induction Period)

Description

Time Frame

Title

Number of Participants With Any Missed Doses of Atezolizumab (Overall Treatment Period)

Description

Time Frame

Title

Number of Participants With Any Dose Interruptions [for Each Study Drug: Trilaciclib/Placebo, Carboplatin and Etoposide] (Induction Period)

Description

Dose interruptions were defined as interruption of infusion, regardless of whether the study drug was continued after the interruption.

Time Frame

Title

Number of Participants With Any Interrupted Doses of Atezolizumab (Overall Treatment Period)

Description

Dose interruptions were defined as interruption of infusion, regardless of whether the study drug was continued after the interruption.

Time Frame

Title

Number of Participants With Any Dose Reductions of Carboplatin and Etoposide (Induction Period)

Description

No dose reductions were allowed for trilaciclib or atezolizumab during the study.

Time Frame

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Contact

Organizational Affiliation

G1 Therapeutics, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Beverly Hills Cancer Center

City

Beverly Hills

State/Province

California

ZIP/Postal Code

90211

Country

United States

Facility Name

St. Jude Heritage Healthcare

City

Fullerton

State/Province

California

ZIP/Postal Code

92835

Country

United States

Facility Name

Loma Linda University

City

Loma Linda

State/Province

California

ZIP/Postal Code

92350

Country

United States

Facility Name

UCLA Medical Center - Santa Monica Hematology And Oncology

City

Santa Monica

State/Province

California

ZIP/Postal Code

90404

Country

United States

Facility Name

Redwood Regional Medical Group (RRMG) - Fountain Grove

City

Santa Rosa

State/Province

California

ZIP/Postal Code

95403

Country

United States

Facility Name

Singing River Health System

City

Whittier

State/Province

California

ZIP/Postal Code

90603

Country

United States

Facility Name

Piedmont Cancer Institute

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30318

Country

United States

Facility Name

Northside Hospital - Georgia Cancer Specialists

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30341

Country

United States

Facility Name

Joliet Oncology-Hematology Associates

City

Joliet

State/Province

Illinois

ZIP/Postal Code

60435

Country

United States

Facility Name

Horizon Oncology Center

City

Lafayette

State/Province

Indiana

ZIP/Postal Code

47905

Country

United States

Facility Name

Ochsner Clinic Foundation

City

New Orleans

State/Province

Louisiana

ZIP/Postal Code

70121

Country

United States

Facility Name

St. Louis Cancer Care, LLP, North County

City

Bridgeton

State/Province

Missouri

ZIP/Postal Code

63044

Country

United States

Facility Name

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

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110-1094

Country

United States

Facility Name

Summit Medical Group, P.A.

City

Morristown

State/Province

New Jersey

ZIP/Postal Code

07962

Country

United States

Facility Name

Northern Westchester Hospital

City

Mount Kisco

State/Province

New York

ZIP/Postal Code

10549

Country

United States

Facility Name

Trinity Health - Trinity CancerCare Center

City

Minot

State/Province

North Dakota

ZIP/Postal Code

58701

Country

United States

Facility Name

Oklahoma University - Peggy and Charles Stephenson Cancer Center

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73117

Country

United States

Facility Name

Gibbs Cancer Center

City

Spartanburg

State/Province

South Carolina

ZIP/Postal Code

29303

Country

United States

Facility Name

Valley Cancer Associates

City

Harlingen

State/Province

Texas

ZIP/Postal Code

78550

Country

United States

Facility Name

Millennium Oncology

City

Houston

State/Province

Texas

ZIP/Postal Code

77090

Country

United States

Facility Name

Virginia Cancer Specialists

City

Arlington

State/Province

Virginia

ZIP/Postal Code

22031

Country

United States

Facility Name

Blue Ridge Cancer Care

City

Blacksburg

State/Province

Virginia

ZIP/Postal Code

24060

Country

United States

Facility Name

Fort Belvoir Community Hospital

City

Fort Belvoir

State/Province

Virginia

ZIP/Postal Code

22060

Country

United States

Facility Name

Complex Oncology Center - Burgas

City

Burgas

ZIP/Postal Code

8000

Country

Bulgaria

Facility Name

Multiprofile Hospital for Active Treatment "Serdika", Sofia

City

Sofia

ZIP/Postal Code

1303

Country

Bulgaria

Facility Name

Multiprofile Hospital for Active Treatment "Serdika"

City

Sofia

ZIP/Postal Code

1303

Country

Bulgaria

Facility Name

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

City

Tallinn

ZIP/Postal Code

11312

Country

Estonia

Facility Name

CHU Caen De La Côte De Nacre

City

Caen

ZIP/Postal Code

14033

Country

France

Facility Name

Centre Oscar Lambret

City

Lille

ZIP/Postal Code

59020

Country

France

Facility Name

Daugavpils Regional Hospital, Department of Oncology

City

Daugavpils

ZIP/Postal Code

LV-5417

Country

Latvia

Facility Name

Pauls Stradiņš Clinical University Hospital, Oncology Clinic

City

Riga

ZIP/Postal Code

LV-1002

Country

Latvia

Facility Name

Hospital Universitario Son Espases

City

Palma

State/Province

Islas Baleares

ZIP/Postal Code

07120

Country

Spain

Facility Name

Hospital Teresa Herrera

City

A Coruña

State/Province

La Coruña

ZIP/Postal Code

15006

Country

Spain

Facility Name

Hospital Universitario Puerta de Hierro Majadahonda

City

Majadahonda

State/Province

Madrid

ZIP/Postal Code

28222

Country

Spain

Facility Name

Hospital Clínico

City

San Carlos

State/Province

Madrid

ZIP/Postal Code

28040

Country

Spain

Facility Name

H.U. Quirón Dexeus, Hospital Universitario

City

Barcelona

ZIP/Postal Code

08028

Country

Spain

Facility Name

Hospital Clinic de Barcelona- Servicio de Oncología Médica

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Facility Name

Hospital Universitario Ramón y Cajal

City

Madrid

ZIP/Postal Code

28034

Country

Spain

Facility Name

Hospital 12 de Octubre

City

Madrid

ZIP/Postal Code

28041

Country

Spain

Facility Name

H. Donostia, Hospital Donostia- Servicio de Oncología

City

San Sebastián

ZIP/Postal Code

20014

Country

Spain

Facility Name

Hospital Universitario Ntra. Sra. de Valme

City

Sevilla

ZIP/Postal Code

41014

Country

Spain

Facility Name

Hospital Arnau de Vilanova

City

Valencia

ZIP/Postal Code

46015

Country

Spain

Facility Name

Chernivtsi Regional Clinical Oncology Center

City

Chernivtsi

ZIP/Postal Code

58013

Country

Ukraine

Facility Name

Dnipropetrovsk City Multispecialty Clinical Hospital #4

City

Dnipro

ZIP/Postal Code

49102

Country

Ukraine

Facility Name

Lviv State Regional Treatment and Diagnostics Oncology Center

City

Lviv

ZIP/Postal Code

79031

Country

Ukraine

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

33348420

Citation

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. 2020 Dec 21;148(10):2557-70. doi: 10.1002/ijc.33453. Online ahead of print.

Results Reference

background

PubMed Identifier

33895103

Citation

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.

Results Reference

background

PubMed Identifier

34873975

Citation

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.

Results Reference

derived

PubMed Identifier

34777341

Citation

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.

Results Reference

derived

PubMed Identifier

34408488

Citation

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.

Results Reference

derived

PubMed Identifier

34405547

Citation

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.

Results Reference

derived

Learn more about this trial

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

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