Small-Cell Lung Cancer MedDRA version: 21.1 Level: PT Classification code 10041068 Term: Small cell lung cancer extensive stage System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: ZEPZELCA
Product Name: Lurbinectedin
Product Code: RO7508182
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: LURBINECTEDIN
Current Sponsor code: RO7508182
Sponsors
F.Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age >= 18 years • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 • Histologically or cytologically confirmed ES-SCLC (per the VALG staging system) • No prior systemic treatment for 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 • Submission of pre-induction therapy tumor sample for exploratory biomarker research • Negative HIV test and no evidence of active Hepatitis B or Hepatitis C at screening • Remain abstinent or use contraception and refrain from donating eggs (women) or donating sperm (men) Inclusion Criteria for the Maintenance Phase • ECOG performance status (PS) of 0 or 1 • Ongoing response or stable disease per RECIST v1.1 after completion of the induction therapy • Randomized within 5 weeks (35 days) from last dose of induction therapy, or if receiving PCI, randomized within 9 weeks (63 days) from last dose of induction therapy • Toxicities attributed to prior induction anti-cancer therapy or PCI resolved to Grade 1 or better • Adequate hematologic and end-organ function • For participants not receiving therapeutic anticoagulation: INR and aPTT =65 years) yes F.1.3.1 Number of subjects for this age range 380
Exclusion criteria
Exclusion criteria: • Participants who are pregnant or breastfeeding, or intending to become pregnant during the study or within 7 months after the final dose of study treatment • Presence or history of CNS metastases • Planned consolidative chest radiation • Uncontrolled tumor-related pain • Uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures • Active or history of autoimmune disease or deficiency • Clinically significant liver disease • 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 Exclusion Criteria for the Maintenance Phase • Presence or history of CNS metastases • Receiving consolidative chest radiation • Lesions that require palliative radiotherapy • Severe infection within 2 weeks prior to randomization into maintenance phase • Major surgical procedure, other than for diagnosis, within 4 weeks prior to randomization • Treatment with therapeutic oral or IV antibiotics at the time of randomization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the efficacy of lurbinectedin in combination with atezolizumab compared with atezolizumab based on Independent Review Facility (IRF)-assessed progression-free survival (PFS) and overall survival (OS);Secondary Objective: •To evaluate the efficacy of lurbinectedin in combination with atezolizumab compared with atezolizumab based on Investigator-assessed PFS, Confirmed objective response rate (ORR), duration of response (DOR), PFS rates at 6 months and 12 months, and overall survival (OS) rates at 12 months and 24 months • To evaluate the safety of lurbinectedin in combination with atezolizumab compared with atezolizumab based on incidence and severity of adverse events • To evaluate the immunogenicity of atezolizumab with and without lurbinectedin based on the prevalence of anti-drug antibodies (ADA) to atezolizumab throughout treatment • To evaluate the health-related quality of life of participants treated with lurbinectedin in combination with atezolizumab compared with atezolizumab ;Primary end point(s): 1. IRF-assessed progression-free survival (PFS) after randomization, 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 2. Overall Survival after randomization, defined as the time from randomization to the date of death from any cause ;Timepoint(s) of evaluation of this end point: 1-2. Up to 60 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Investigator-assessed progression-free survival (PFS) 2. Confirmed objective response rate (ORR) as determined by the IRF and investigator according to RECIST v1.1 3. Duration of response (DOR) as determined by the IRF and investigator according to RECIST v1.1, or death from any cause, whichever occurs first 4. PFS rates at 6 months and 12 months as determined by the IRF and investigator according to RECIST v1.1 5. OS rates at 12 months and 24 months 6. Incidence and severity of adverse events, including serious adverse events and adverse events of special interest in randomized participants, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 7. Prevalence of anti-drug antibodies (ADAs) to atezolizumab at induction phase baseline and incidence of ADAs to atezolizumab after drug administration by treatment group 8. 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 Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30;Timepoint(s) of evaluation of this end point: 1-3. Up to 60 months 4. At 6 months and 12 months after randomization 5. At 12 months and 24 months after randomization 6. Up to 60 months 7. Induction Phase: Day 1 of Cycle 1-4; Maintenance Phase: Day 1 of Cycle 1-4, 8, 12, and 16, </= 30 days after treatment discontinuation 8. Induction Phase: Day 1 of Cycle 1-4; Maintenance Phase: Day 1 of Cycle 1, </=30 Days after the last dose of study treatment, at treatment discontinuation visit, post treatment follow-up visit | — |
Countries
Belgium, Germany, Greece, Hungary, Italy, Korea, Republic of, Poland, Russian Federation, Spain, Taiwan, Türkiye, Ukraine, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd.
Outcome results
None listed