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Clinical Trial NCT06712355 for Extensive-stage Small-cell Lung Cancer is recruiting. See the Trial Radar Card View and AI discovery tools for all the details. Or ask anything here. | ||
Safety and Efficacy of BNT327, an Investigational Therapy in Combination With Chemotherapy for Patients With Untreated Small-cell Lung Cancer Phase 3 621 Randomized Double-Blind
Each stage of 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 term...
Show MoreA Phase III, Multisite, Double-blinded Randomized Trial of BNT327 in Combination With Chemotherapy (Etoposide/Carboplatin) Compared to Atezolizumab in Combination With Chemotherapy (Etoposide/Carboplatin) in Participants With First-line Extensive-stage Small-cell Lung Cancer
- BNT327-03
- 2024-515765-34-00 (EU Study (CTIS) Number)
SCLC
Immunotherapy in combination with chemotherapy
Untreated
Bispecific antibody
Programmed death-ligand 1 (PD-L1)
Vascular endothelial growth factor (VEGF) A
Immunotherapy
Combination with other investigational agents
Pumitamig
BNT327
Check point inhibitor
Lung cancer
Etoposide
Carboplatin
Cisplatin
| Participant Group/Arm | Intervention/Treatment |
|---|---|
Active ComparatorStage 1 Control Arm - Atezolizumab + Etoposide + Carboplatin | Atezolizumab Intravenous infusion Etoposide Intravenous infusion and capsules Carboplatin (or cisplatin if carboplatin is not tolerated) Intravenous infusion |
ExperimentalStage 1 Treatment Arm 1 - Pumitamig Dose 1 + Etoposide + Carboplatin | Pumitamig Intravenous infusion Etoposide Intravenous infusion and capsules Carboplatin (or cisplatin if carboplatin is not tolerated) Intravenous infusion |
ExperimentalStage 1 Treatment Arm 2 - Pumitamig Dose 2 + Etoposide + Carboplatin | Pumitamig Intravenous infusion Etoposide Intravenous infusion and capsules Carboplatin (or cisplatin if carboplatin is not tolerated) Intravenous infusion |
Active ComparatorStage 2 Control Arm - Atezolizumab + Etoposide + Carboplatin | Atezolizumab Intravenous infusion Etoposide Intravenous infusion and capsules Carboplatin (or cisplatin if carboplatin is not tolerated) Intravenous infusion |
ExperimentalStage 2 Treatment Arm - Pumitamig Dose 3 + Etoposide + Carboplatin | Pumitamig Intravenous infusion Etoposide Intravenous infusion and capsules Carboplatin (or cisplatin if carboplatin is not tolerated) Intravenous infusion |
| Outcome Measure | Measure Description | Time Frame |
|---|---|---|
Overall survival (OS) | OS defined as the time from randomization to death from any cause. | Up to approximately 46 months |
| Outcome Measure | Measure Description | Time Frame |
|---|---|---|
Progression-free survival (PFS) | 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. | Up to approximately 46 months |
Objective response rate (ORR) | 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. | Up to approximately 46 months |
Duration of response (DOR) | DOR defined as the time from onset of objective response (confirmed CR or PR based on investigator's assessment per RECIST v1.1) to first occurrence of objective tumor progression (progressive disease per RECIST v1.1) or death from any cause, whichever occurs first. | Up to approximately 46 months |
PFS rate based on investigator's assessment | At 6, 12, and 18 months | |
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 | TEAEs graded according to (US) National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 | From the first dose of study treatment to the 90-Day Follow-up Visit |
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) | 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). | Up to approximately 46 months |
Change from baseline in EORTC QLQ-C30 physical functioning | 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). | Up to approximately 46 months |
Change from baseline in coughing scale of the EORTC Quality-of-Life-Lung cancer 29 questionnaire (QLQ-LC29) | Multi-item coughing scale ranges in score from 0 to 100 with a high score representing a high level of symptomatology or problems. | Up to approximately 46 months |
Change from baseline in shortness of breath scale of the EORTC QLQ-LC29 | 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. | Up to approximately 46 months |
Change from baseline in coughed up blood item of the EORTC QLQ-LC29 | Single item coughing up blood ranges in score from 0 to 100 with a high score representing a high level of symptomatology or problems. | Up to approximately 46 months |
Change from baseline in Functional Assessment of Cancer Therapy-General overall bother item (FACT-GP5). | The FACT-G - Item GP5 (Version 4) is a single-item summary measure of the overall impact of treatment toxicity, based upon its association with the number and degree of AEs in clinical studies, rated on a 5-point Likert scale ("not at all" to "very much") with a recall period of past 7 days. A high score represents high level of problems. | Up to approximately 46 months |
- 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 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 chemotherapy, radiotherapy, 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 as defined in the protocol.
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 outside the thoracic cavity including whole brain radiation. Of note, other local radiation for brain lesions (not whole brain) is allowed; local radiation for bone lesions is allowed. Palliative bone radiation or brain stereotactic radiosurgery would not require a washout period, but participants should recover from radiotherapy-related toxicity.
- 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 anti-vascular endothelial growth factor (VEGF) monoclonal antibody, or programmed death (ligand)-1 (PD\[L\]-1)/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 7 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 (at a dosage greater than 10 mg/Day of prednisone or an equivalent dose of other corticosteroid) within 7 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 a serious or non-healing wound, or (incompletely healed) 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 a significant risk of hemorrhage (per investigator clinical judgment) as defined in the protocol.
Have superior vena cava syndrome or symptoms of spinal cord compression that requires urgent medical intervention.
NOTE: Other protocol defined Inclusion/Exclusion criteria apply.
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