NIPH Clinical Trials Search

A Phase II/III, multisite, randomized master protocol for a global trial of BNT327 in combination with chemotherapy and other investigational agents in first-line non-small cell lung cancer

Basic Information

Recruitment status	Recruiting
Health condition(s) or Problem(s) studied	Non-small Cell Lung Cancer
Date of first enrollment	01/07/2025
Target sample size	982
Countries of recruitment	Australia,Japan,Belgium,Japan,China,Japan,France,Japan,Georgia,Japan,Germany,Japan,Italy,Japan,Poland,Japan,Romania,Japan,South Koria,Japan,Spain,Japan,Switzerland,Japan,Thailand,Japan,Turkey,Japan,UK,Japan,US,Japan
Study type	Interventional
Intervention(s)	Substudy A (non-squamous NSCLC) Phase 2 - BNT327 Dose 1 + Carboplatin + Pemetrexed - BNT327 Dose 2 + Carboplatin + Pemetrexed Phase 3 - BNT327 + Carboplatin + Pemetrexed (BNT327 selected dose for Phase 3) - Pembrolizumab + Carboplatin + Pemetrexed (Active Comparator) Substudy B (squamous NSCLC) Phase 2 - BNT327 Dose 1 + Carboplatin + Paclitaxel - BNT327 Dose 2 + Carboplatin + Paclitaxel Phase 3 - BNT327 + Carboplatin + Paclitaxel (BNT327 selected dose for Phase 3) - Pembrolizumab + Carboplatin + Paclitaxel (Active Comparator)

Outcome(s)

Primary Outcome

Phase 2 (For substudies A (non-squamous NSCLC) and B (squamous NSCLC)) - Occurrence of treatment-emergent adverse events (TEAE) (including Grade >=3), adverse events of special interest (AESIs), treatment-related TEAEs, treatment-emergent serious adverse events (SAE), and treatment-related treatment emergent SAEs [Time Frame: From the first dose of the investigational medicinal product (IMP) to the 90-day Follow-Up Visit] - Occurrence of dose interruption, reduction, and discontinuation of IMP due to TEAEs (including related TEAEs) [Time Frame: From the first dose of IMP to the 90-day Follow-Up Visit] - Objective response rate (ORR) - unconfirmed [Time Frame: Up to approximately 2 years] - Best percentage change from baseline in tumor size [Time Frame: Up to approximately 2 years] Phase 3 (For substudies A and B) - Progression free survival (PFS) assessed by blinded independent central review (BICR) [Time Frame: Up to approximately 5 years] - Overall survival (OS) [Time Frame: Up to approximately 5 years]

Secondary Outcome

Phase 2 (For substudies A and B) - ORR - confirmed [Time Frame: Up to approximately 2 years] - Duration of Response (DOR) [Time Frame: Up to approximately 2 years] - Disease Control Rate (DCR) [Time Frame: Up to approximately 2 years] Phase 3 (For substudies A and B) - PFS assessed by investigator [Time Frame: Up to approximately 5 years] - ORR assessed by BICR and by the investigator [Time Frame: Up to approximately 2 years] - DOR assessed by BICR and by the investigator [Time Frame: Up to approximately 2 years] - DCR assessed by BICR and by the investigator [Time Frame: Up to approximately 2 years] - PFS rate as assessed by BICR [Time Frame: At 6, 12, and 18 months] - PFS rate as assessed by investigator [Time Frame: At 6, 12, and 18 months] - OS rate [Time Frame: At 6, 12, 18, 24 months] - Change from baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-life-Core 30 Questionnaire (QLQ-C30) [Time Frame: Up to approximately 5 years] - Change from baseline in EORTC Lung Cancer-Specific QoL Questionnaire (QLC-LC29) [Time Frame: Up to approximately 5 years] - Change from baseline in Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) total score and domain score [Time Frame: Up to approximately 5 years] - Occurrence of TEAEs including Grade >=3, serious, and fatal TEAEs by relationship [Time Frame: From the first dose of IMP to the 90-day Follow-Up Visit] - Occurrence of dose interruption, reduction, and discontinuation of IMP due to TEAEs (including related TEAEs) [Time Frame: From the first dose of IMP to the 90-day Follow-Up Visit]

Key inclusion & exclusion criteria

Age minimum	>= 18age old
Age maximum	Not applicable
Gender	Both
Include criteria	-Have histologically or cytologically confirmed diagnosis of Stage IIIB or IIIC (who are not amenable to curative surgery or radiotherapy) or Stage IV NSCLC per the Union Internationale contre le Cancer/American Joint Committee on Cancer staging system, 8th edition without actionable EGFR mutation or anaplastic lymphoma kinase rearrangement. -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 organ function. NOTE: Other protocol defined Inclusion criteria may apply.
Exclude criteria	-Have histologically or cytologically confirmed NSCLC with small-cell lung cancer histologic component. -Have received any of the following therapies or drugs within the noted time intervals prior to study treatment: -Participants who received prior treatment with anti-VEGF monoclonal antibody, or PD(L)-1/VEGF bispecific antibody or received platinum-based chemotherapy and/or anti-PD(L)-1 as part of adjuvant or neoadjuvant treatment -Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 14 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 uncontrolled hypertension or poorly controlled diabetic conditions prior to study treatment. -Have a serious non-healing wound, ulcer, or bone fracture. This includes history (within 6 months prior to study entry) or risk of abdominal fistula, tracheoesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess. In addition, the participant must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing fistula/perforation. -Participants with evidence of major coagulation disorders or other significant risks of hemorrhage. -Have superior vena cava syndrome or symptoms of spinal cord compression. NOTE: Other protocol defined Exclusion criteria may apply.