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 (IMforte)

• ClinicalTrials.gov Identifier: NCT05091567
• Recruitment Status: Active, not recruiting
• First Posted: October 25, 2021
• Last Update Posted: March 12, 2024
• Sponsor: Hoffmann-La Roche
• Collaborator: Jazz Pharmaceuticals
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: October 12, 2021
• First Posted Date: October 25, 2021
• Last Update Posted Date: March 12, 2024
• Actual Study Start Date: November 18, 2021
• Estimated Primary Completion Date: April 18, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 9, 2024)

• IRF-Assessed Progression-Free Survival (PFS) [ Time Frame: Randomization to the date of first documented disease progression or death, whichever occurs first (up to approximately 60 months) ]
  IRF-assessed progression-free survival (PFS) is defined as the time from randomization to the date of first documented disease progression (as assessed by the IRF according to RECIST v1.1), or death whichever occurs first.
• Overall Survival (OS) [ Time Frame: Randomization to the date of death from any cause (up to approximately 60 months) ]
  Overall survival (OS) is defined as the time from randomization to the date of death from any cause.

Original Primary Outcome Measures (submitted: October 12, 2021)

• IRF-Assessed Progression-Free Survival (PFS) [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause (whichever occurs first)(up to approximately 52 months) ]
  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).
• Overall Survival (OS) [ Time Frame: Randomization to death from any cause (up to approximately 52 months) ]
  Overall survival (OS) is defined as the time from randomization to death from any cause.

Current Secondary Outcome Measures (submitted: February 9, 2024)

• Investigator-Assessed PFS [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause (whichever occurs first)(up to approximately 60 months) ]
  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).
• Confirmed Objective Response Rate (ORR) as Determined by the IRF [ Time Frame: Up to approximately 60 months ]
  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 according to RECIST v1.1.
• Confirmed Objective Response Rate (ORR) as Determined by the Investigator [ Time Frame: Up to approximately 60 months ]
  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 Investigator according to RECIST v1.1.
• Duration of Response (DOR) as Determined by the IRF [ Time Frame: Up to approximately 60 months ]
  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 according to RECIST v1.1, or death from any cause, whichever occurs first.
• Duration of Response (DOR) as Determined by the Investigator [ Time Frame: Up to approximately 60 months ]
  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 investigator according to RECIST v1.1, or death from any cause, whichever occurs first.
• PFS Rates as Determined by the IRF [ Time Frame: 6 months and 12 months after randomization ]
  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 according to RECIST v1.1.
• PFS Rates as Determined by the Investigator [ Time Frame: 6 months and 12 months after randomization ]
  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 investigator according to RECIST v1.1.
• OS Rates [ Time Frame: 12 months and 24 months after randomization ]
  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.
• Percentage of Participants With Adverse Events [ Time Frame: Up to approximately 60 months ]
  Percentage of participants with adverse events.
• Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab [ Time Frame: Up to approximately 60 months ]
  Percentage of participants with ADAs to atezolizumab after drug administration.
• Time to Confirmed Deterioration (TTCD) [ Time Frame: Up to approximately 60 months ]
  Time to confirmed deterioration (TTCD) from randomization 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).

Original Secondary Outcome Measures (submitted: October 12, 2021)

• Investigator-Assessed PFS [ Time Frame: Randomization to the first occurrence of disease progression or death from any cause (whichever occurs first)(up to approximately 52 months) ]
  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).
• Confirmed Objective Response Rate (ORR) [ Time Frame: Up to approximately 52 months ]
  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.
• Duration of Response (DOR) [ Time Frame: Up to approximately 52 months ]
  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).
• PFS Rates [ Time Frame: 6 months and 12 months after randomization ]
  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.
• OS Rates [ Time Frame: 12 months and 24 months after randomization ]
  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.
• Percentage of Participants With Adverse Events [ Time Frame: Up to approximately 52 months ]
  Percentage of participants with adverse events.
• Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab [ Time Frame: Up to approximately 52 months ]
  Percentage of participants with ADAs to atezolizumab after drug administration.
• Time to Confirmed Deterioration (TTCD) [ Time Frame: Maintenance phase baseline ]
  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).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Small-Cell Lung Cancer

Intervention

• Drug: Atezolizumab
  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.
  Other Name: Tecentriq, RO5541267
• Drug: Lurbinectedin
  Lurbinectedin 3.2 mg/m² will be administered intravenously on Day 1 of each 21-day cycle in the maintenance phase.
  Other Name: PM01183/JZP712
• Drug: Carboplatin
  Carboplatin will be administered according to the standard of care treatment for 4 cycles in the induction phase.
• Drug: Etoposide
  Etoposide will be administered according to the standard of care treatment for 4 cycles in the induction phase.

Study Arms

• Experimental: 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.

  Interventions:

  • Drug: Atezolizumab
  • Drug: Lurbinectedin
  • Drug: Carboplatin
  • Drug: Etoposide
• Active Comparator: 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.

  Interventions:

  • Drug: Atezolizumab
  • Drug: Carboplatin
  • Drug: Etoposide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: October 12, 2021): 690
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 6, 2026
• Estimated Primary Completion Date: April 18, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Germany, Greece, Hungary, Italy, Korea, Republic of, Mexico, Poland, Spain, Taiwan, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05091567
• Other Study ID Numbers: GO43104
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Jazz Pharmaceuticals

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: March 2024