Safety and Effectiveness of BNT327, an Investigational Therapy in Combination With Chemotherapy for Patients With Untreated Small-cell Lung Cancer
- Conditions
- Extensive-stage Small-cell Lung Cancer
- Interventions
- Registration Number
- NCT06712355
- Lead Sponsor
- BioNTech SE
- Brief Summary
This is a Phase III, multisite, randomized, double-blinded study to investigate BNT327 combined with chemotherapy (etoposide/carboplatin) compared to atezolizumab combined with chemotherapy (etoposide/carboplatin) for the treatment of participants with previously untreated extensive-stage small-cell lung cancer (ES-SCLC).
- Detailed Description
The study consists of a screening period (up to 21 days), an induction period followed by a maintenance period (until confirmed disease progression, intolerable toxicity, participant withdrawal, study termination or up to 2 years \[whichever occurs first\]), and a follow-up (FU) period for all participants (2 safety FU visits and survival FU visits).
Eligible patients will be randomized (1:1:1) to the treatment arms (Arm 1, Arm 2, and Arm 3), until one arm stops accrual. Participants will then be randomized (1:1) in the remaining two treatment arms (Arm 1 and Arm 2 or Arm 3). The randomization will be stratified based on the following factors:
1. Brain metastases per investigator assessment;
2. Liver metastases per investigator assessment; and
3. Geography.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 439
-
Have histologically or cytologically confirmed ES-SCLC (using the AJCC [American Joint Committee on Cancer] tumor node metastasis staging system combined with Veterans Administration Lung Study Group [VALG]'s two stage classification scheme).
- For AJCC tumor node metastasis staging system: AJCC 8th edition stage IV (T any, N any, M1a/b/c), or T3~4 for multiple lung nodules or tumor/nodule volume that cannot be encompassed in a tolerable radiotherapy plan.
-
Have not had prior systemic therapy for ES-SCLC. However, participants with prior chemoradiotherapy or immunotherapy for limited-stage-SCLC must have been treated with curative intent and had a treatment-free interval of at least 6 months after the last systemic anticancer treatment including chemotherapy, radiotherapy, immunotherapy, or chemoradiotherapy before diagnosis of ES-SCLC to be eligible.
-
Have at least one measurable lesion as the targeted lesion based on RECIST v1.1. Lesions treated after prior local treatment (radiotherapy, ablation, interventional procedures, etc.) are generally not considered as target lesions. If the lesion with prior local treatment is the only targeted lesion, evidence-based radiology must be provided to demonstrate disease progression (the single bone metastasis or the single central nervous system metastasis should not be considered as a measurable lesion).
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
-
Adequate hematologic and organ function.
-
Have histologically or cytologically confirmed SCLC with combined histologies.
-
Have received any of the following therapies or drugs within the noted time intervals prior to study treatment:
- Within 2 weeks: small molecule agents with half-life of <7 days; radiation not involving the thoracic cavity; local radiation for brain lesions is allowed; local radiation for bone lesions is allowed.
- Within 4 weeks: radiation involving the thoracic cavity; small molecule targeted agents with half-life of ≥7 days; monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or T-cell or other cell-based therapies.
- Have received prior treatment with a programmed death (ligand)-1 (PD[L]-1)/vascular endothelial growth factor (VEGF) bispecific antibody.
- Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 10 days prior to the initiation of study treatment. Note: local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short-term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens) are allowed.
-
Have the following central nervous system metastases:
- Participants with untreated brain metastases that are symptomatic or large (e.g., greater than 2 cm).
- Participants with treated central nervous system (CNS) metastases who are not neurologically stable or on steroids within 10 days before initiating study treatment of this study.
- Participants with known leptomeningeal metastases.
-
Have uncontrolled hypertension or poorly controlled diabetes prior to study treatment.
-
Have serious non-healing wound, ulcer, or bone fracture. This includes history of abdominal fistula, tracheoesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess for which an interval of 6 months must pass before study entry. In addition, the participant must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the fistula/perforation.
-
Have evidence of major coagulation disorders or other significant risks of hemorrhage such as:
- History of intracranial or intraspinal hemorrhage.
- Tumor lesions invading large vessels and with significant risk of bleeding.
- Had clinically significant hemoptysis or tumor hemorrhage within 1 month prior to the study treatment.
-
Have superior vena cava syndrome or symptoms of spinal cord compression.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1 - Atezolizumab + Etoposide + Carboplatin Atezolizumab - Arm 1 - Atezolizumab + Etoposide + Carboplatin Etoposide - Arm 1 - Atezolizumab + Etoposide + Carboplatin Carboplatin - Arm 2 - BNT327 Dose 1 + Etoposide + Carboplatin Etoposide - Arm 2 - BNT327 Dose 1 + Etoposide + Carboplatin Carboplatin - Arm 3 - BNT327 Dose 2 + Etoposide + Carboplatin BNT327 - Arm 3 - BNT327 Dose 2 + Etoposide + Carboplatin Etoposide - Arm 3 - BNT327 Dose 2 + Etoposide + Carboplatin Carboplatin - Arm 2 - BNT327 Dose 1 + Etoposide + Carboplatin BNT327 -
- Primary Outcome Measures
Name Time Method Overall survival (OS) Up to approximately 39 months OS defined as the time from randomization to death from any cause.
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) Up to approximately 39 months PFS defined as the time from randomization to first objective tumor progression (progressive disease per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\]), or death from any cause, whichever occurs first.
PFS rate based on investigator's assessment At 6, 12, and 18 months Objective response rate (ORR) Up to approximately 39 months ORR defined as the proportion of participants in whom a complete response (CR) or partial response (PR) (based on investigator's assessment per RECIST v1.1) is observed as best overall response with confirmation.
OS rate At 6, 12, 18, and 24 months Occurrence of treatment-emergent adverse events (TEAEs) including Grade ≥3, serious, and fatal TEAEs by relationship From the first dose of study treatment to the 90-Day Follow-up Visit TEAEs graded according to (US) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0)
Occurrence of dose delay, infusion interruption and discontinuation of study treatment due to TEAEs (including related TEAEs) From first to last dose of study treatment, i.e., up to 2 years Change from baseline in European Organisation for Research and Treatment of Cancer (EORTC) quality-of-life Core 30 questionnaire (QLQ-C30) Global Health status/Quality-of-Life score (Items 29 and 30) Up to approximately 39 months Global health status/QoL scale ranges in score from 0 to 100 with a high scale score representing a higher response level (e.g., high score for global health status/QoL is high QoL: high score for symptom scale/item is high symptomatology or problems).
Change from baseline in EORTC QLQ-C30 physical functioning Up to approximately 39 months Physical functioning scale ranges in score from 0 to 100 with a high scale score representing a higher response level (e.g., high score for functional scale is high/healthy level of functioning).
Change from baseline in coughing scale of the EORTC quality-of-life-Lung cancer 29 questionnaire (QLQ-LC29) Up to approximately 39 months Multi-item coughing scale ranges in score from 0 to 100 with a high score representing a high level of symptomatology or problems.
Change from baseline in shortness of breath scale of the EORTC QLQ-LC29 Up to approximately 39 months Multi-item shortness of breath scale ranges in score from 0 to 100 with a high score representing a high level of symptomatology or problems.
Change from baseline in coughed up blood item of the EORTC QLQ-LC29 Up to approximately 39 months Single item coughing up blood ranges in score from 0 to 100 with a high score representing a high level of symptomatology or problems.
Change from baseline in fatigue domain score scale of the NSCLC-SAQ Up to approximately 39 months NSCLC-SAQ consists of seven items assessing 5 NSCLC symptom concepts: cough, pain, dyspnea, fatigue, and poor appetite. All items have a recall period of past 7 days and a 5-point response scale ranging from 0: "No symptom at all" to 4: "Very severe symptom" or from 0: "Never" to 4: "Always" to measure attributes of symptom intensity or frequency, respectively.
Two fatigue items form a single "Fatigue" domain by calculating their mean. Higher scores indicate more severe symptomatology.Change from baseline in pain domain score of the Non-Small-Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) Up to approximately 39 months NSCLC-SAQ consists of seven items assessing 5 NSCLC symptom concepts: cough, pain, dyspnea, fatigue, and poor appetite. All items have a recall period of past 7 days and a 5-point response scale ranging from 0: "No symptom at all" to 4: "Very severe symptom" or from 0: "Never" to 4: "Always" to measure attributes of symptom intensity or frequency, respectively.
Two pain items form a single "Pain" domain representing the most severe response of the two items. Higher scores indicate more severe symptomatology.
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Trial Locations
- Locations (9)
University of Tennessee Medical Center
🇺🇸Knoxville, Tennessee, United States
Peninsula & South Eastern Haematology and Oncology Group
🇦🇺Frankston, Australia
St James's University Hospital - Leeds Teaching Hospitals NHS Trust
🇬🇧Leeds, United Kingdom
Icon Cancer Centre Kurralta Park
🇦🇺Kurralta Park, Australia
Clermont Oncology Center
🇺🇸Clermont, Florida, United States
Fort Wayne Medical Oncology and Hematology, Inc
🇺🇸Fort Wayne, Indiana, United States
Nebraska Hematology-Oncology (NHO)
🇺🇸Lincoln, Nebraska, United States
Hematology Oncology Associates of Fredericksburg, Inc.
🇺🇸Fredericksburg, Virginia, United States
Millennium Research and Clinical Development, LLC
🇺🇸Houston, Texas, United States