A Phase III, Open-Label Study of Maintenance Lurbinectedin in Combination With Atezolizumab Compared With Atezolizumab in Participants With Extensive-Stage Small-Cell Lung Cancer

Study Overview
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Brief Summary
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Study GO43104 is a Phase III, randomized, open-label, multicenter study of lurbinectedin in combination with atezolizumab compared with atezolizumab alone administered as maintenance therapy in participants with extensive-stage small-cell lung cancer (ES-SCLC) after first-line induction therapy with carboplatin, etoposide, and atezolizumab. The study consists of 2 phases: an induction phase and a maintenance phase. Participants need to have an ongoing response or stable disease per the Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 criteria after completion of 4 cycles of carboplatin, etoposide, and atezolizumab induction treatment in order to be considered for eligibility screening for the maintenance phase. Eligible participants will be randomized in a 1:1 ratio to receive either lurbinectedin plus atezolizumab or atezolizumab in the maintenance phase.

Official Title
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A Phase III, Randomized, Open-Label, Multicenter Study of Lurbinectedin in Combination With Atezolizumab Compared With Atezolizumab as Maintenance Therapy in Participants With Extensive-Stage Small-Cell Lung Cancer (ES-SCLC) Following First-Line Induction Therapy With Carboplatin, Etoposide and Atezolizumab

Conditions
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Small-Cell Lung Cancer

Intervention / Treatment
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* Drug: Atezolizumab
* Drug: Lurbinectedin
* Drug: Carboplatin
* Drug: Etoposide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for the Induction Phase: ECOG PS of 0 or 1 No prior systemic therapy for ES-SCLC Treatment-free for at least 6 months since last chemo/radiotherapy, among those treated (with curative intent) with prior chemo/radiotherapy for limited-stage SCLC Histologically or cytologically confirmed ES-SCLC Adequate hematologic and end-organ function to receive 4 cycles of induction treatment with carboplatin, etoposide and atezolizumab Measurable disease, as defined by RECIST v1.1 Negative HIV test and no evidence of active Hepatitis B or Hepatitis C at screening Exclusion Criteria for the Induction Phase: Presence or history of CNS metastases Active or history of autoimmune disease or deficiency History of malignancies other than SCLC within 5 years prior to enrollment Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, or lurbinectedin or trabectedin History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan Treatment with investigational therapy within 28 days prior to enrollment Inclusion Criteria for the Maintenance Phase: ECOG PS of 0 or 1 Ongoing response or stable disease per RECIST 1.1 after 4 cycles of induction therapy Toxicities attributed to prior induction anti-cancer therapy or PCI resolved to Grade <=1 Adequate hematologic and end-organ function Exclusion Criteria for the Maintenance Phase: Presence or history of CNS metastases Receiving consolidative chest radiation Severe infection within 2 weeks prior to randomization into the maintenance Treatment with therapeutic oral or IV antibiotics at the time of randomization

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Atezolizumab+Lurbinectedin<br>Induction phase: participants will receive standard of care atezolizumab on Day 1 of each 21-day cycle in combination with carboplatin on Day 1 and etoposide on Days 1, 2, and 3 of each 21-day cycle for 4 cycles. Maintenance phase: participants will receive atezolizumab on Day 1 of each 21-day cycle in combination with lurbinectedin on Day 1 of each 21-day cycle. | Drug: Atezolizumab<br>* Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle for 4 cycles in the induction phase. Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle in the maintenance phase.<br>* Other names: Tecentriq, RO5541267;Drug: Lurbinectedin<br>* Lurbinectedin 3.2 mg/m² will be administered intravenously on Day 1 of each 21-day cycle in the maintenance phase.<br>* Other names: PM01183/JZP712;Drug: Carboplatin<br>* Carboplatin will be administered according to the standard of care treatment for 4 cycles in the induction phase.<br>Drug: Etoposide<br>* Etoposide will be administered according to the standard of care treatment for 4 cycles in the induction phase.<br>|
| Active Comparator: Arm B: Atezolizumab<br>Induction phase: participants will receive standard of care atezolizumab on Day 1 of each 21-day cycle in combination with carboplatin on Day 1 and etoposide on Days 1, 2, and 3 of each 21-day cycle for 4 cycles. Maintenance phase: participants will receive atezolizumab on Day 1 of each 21-day cycle. | Drug: Atezolizumab<br>* Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle for 4 cycles in the induction phase. Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle in the maintenance phase.<br>* Other names: Tecentriq, RO5541267;Drug: Carboplatin<br>* Carboplatin will be administered according to the standard of care treatment for 4 cycles in the induction phase.<br>Drug: Etoposide<br>* Etoposide will be administered according to the standard of care treatment for 4 cycles in the induction phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IRF-Assessed Progression-Free Survival (PFS) | IRF-assessed progression-free survival (PFS) is defined as the time from randomization to the first occurrence of disease progression as determined by the IRF according to RECIST v1.1, or death from any cause (whichever occurs first). | Randomization to the first occurrence of disease progression or death from any cause (whichever occurs first)(up to approximately 52 months) | 
| Overall Survival (OS) | Overall survival (OS) is defined as the time from randomization to death from any cause. | Randomization to death from any cause (up to approximately 52 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-Assessed PFS | Investigator-assessed PFS is defined as the time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first). | Randomization to the first occurrence of disease progression or death from any cause (whichever occurs first)(up to approximately 52 months) | 
| Confirmed Objective Response Rate (ORR) | Confirmed objective response rate (ORR) is defined as the proportion of randomized participants with a CR or PR on two consecutive occasions >= 4 weeks apart after randomization, as determined by the IRF and the investigator according to RECIST v1.1. | Up to approximately 52 months | 
| Duration of Response (DOR) | Duration of Response (DOR) (for participants with a confirmed objective response) is defined as the time from the first occurrence of a documented confirmed objective response after randomization until disease progression as determined by the IRF and the investigator according to RECIST v1.1, or death from any cause (whichever occurs first). | Up to approximately 52 months | 
| PFS Rates | PFS rates at 6 months and 12 months is defined as the proportion of participants who have not experienced disease progression or death from any cause at 6 months and 12 months after randomization, as determined by the IRF and the investigator according to RECIST v1.1. | 6 months and 12 months after randomization | 
| OS Rates | OS rates at 12 months and 24 months is defined as the proportion of participants who have not experienced death from any cause at 12 months and 24 months after randomization. | 12 months and 24 months after randomization | 
| Percentage of Participants With Adverse Events | Percentage of participants with adverse events. | Up to approximately 52 months | 
| Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab | Percentage of participants with ADAs to atezolizumab after drug administration. | Up to approximately 52 months | 
| Time to Confirmed Deterioration (TTCD) | Time to confirmed deterioration (TTCD) from maintenance baseline in participant-reported physical functioning and global health status as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30). | Maintenance phase baseline |