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
Trial Snapshot
- Phase
- Phase 3
- Status
- Active, not recruiting
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 660
- Locations
- 147
- Primary Endpoint
- Randomized Phase: Independent Review Facility (IRF) - Assessed Progression Free Survival (PFS)
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Arm A: Atezolizumab+Lurbinectedin
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.
Intervention: Etoposide (Drug)
Arm B: Atezolizumab
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.
Intervention: Atezolizumab (Drug)
Arm A: Atezolizumab+Lurbinectedin
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.
Intervention: Atezolizumab (Drug)
Arm A: Atezolizumab+Lurbinectedin
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.
Intervention: Lurbinectedin (Drug)
Arm A: Atezolizumab+Lurbinectedin
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.
Intervention: Carboplatin (Drug)
Arm B: Atezolizumab
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.
Intervention: Carboplatin (Drug)
Arm B: Atezolizumab
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.
Intervention: Etoposide (Drug)
Outcomes
Primary Outcomes
Randomized Phase: Independent Review Facility (IRF) - Assessed Progression Free Survival (PFS)
Time Frame: Up to 26 months
PFS was defined as the time from randomization to the date of first documented PD as determined by the IRF according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or death, whichever occurs first. PD was defined as appearance of a new lesion(s), unequivocal progression in non-target lesion(s) or at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest sum on the study including baseline (nadir). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimetres (mm).
Randomized Phase: Independent Review Facility (IRF) - Assessed Progression Free Survival (PFS)
Time Frame: Up to 26 months
PFS was defined as the time from randomization to the date of first documented PD as determined by the IRF according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or death, whichever occurs first. PD was defined as appearance of a new lesion(s), unequivocal progression in non-target lesion(s) or at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest sum on the study including baseline (nadir). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimetres (mm).
Randomized Phase: Overall Survival (OS)
Time Frame: Up to 26 months
OS was defined as the time from randomization to the date of death from any cause.
Secondary Outcomes
- Randomized Phase: Confirmed ORR as Determined by the Investigator(Up to 26 months)
- Randomized Phase: Confirmed Objective Response Rate (ORR) as Determined by the IRF(Up to 26 months)
- Randomized Phase: Duration of Response (DOR) as Determined by the IRF(Up to 26 months)
- Randomized Phase: DOR as Determined by the Investigator(Up to 26 months)
- Randomized Phase: Percentage of Participants With PFS as Determined by the IRF at 6 Months and 12 Months(Months 6 and 12)
- Randomized Phase: Percentage of Participants With PFS Determined by Investigator at 6 Months and 12 Months(Months 6 and 12)
- Randomized Phase: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)(Up to 26 months)
- Randomized Phase: Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab(Up to 26 months)
- Randomized Phase: Time to Confirmed Deterioration (TTCD) in Physical Functioning (PF) and Global Health Status (GHS) as Measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQC30)(Up to 26 months)
- Randomized Phase: Investigator-assessed PFS(Up to 26 months)
- Randomized Phase: Confirmed Objective Response Rate (ORR) as Determined by the IRF(Up to 26 months)
- Randomized Phase: Confirmed ORR as Determined by the Investigator(Up to 26 months)
- Randomized Phase: Duration of Response (DOR) as Determined by the IRF(Up to 26 months)
- Randomized Phase: DOR as Determined by the Investigator(Up to 26 months)
- Randomized Phase: Percentage of Participants With PFS as Determined by the IRF at 6 Months and 12 Months(Months 6 and 12)
- Randomized Phase: Percentage of Participants With PFS Determined by Investigator at 6 Months and 12 Months(Months 6 and 12)
- Randomized Phase: Percentage of Participants With OS at 12 Months and 24 Months(Months 12 and 24)
- Randomized Phase: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)(Up to 26 months)
- Randomized Phase: Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab(Up to 26 months)
- Randomized Phase: Time to Confirmed Deterioration (TTCD) in Physical Functioning (PF) and Global Health Status (GHS) as Measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQC30)(Up to 26 months)