Safety, Effectiveness, and Pharmacokinetics (the Movement of Drug Into, Through and Out of the Body) of BNT327 (an Investigational Therapy) in Combination With Chemotherapy and Other Investigational Agents for Lung Cancer
- Conditions
- Interventions
- Registration Number
- NCT06712316
- Lead Sponsor
- BioNTech SE
- Brief Summary
This is a Phase 2/3, multisite, randomized, open-label study in participants with first-line non-small cell lung cancer (NSCLC).
This study includes two substudies (substudy A and substudy B) that will recruit participants according to histological subtypes due to differences in chemotherapy choice for standard-of-care and type of NSCLC.
- Detailed Description
Each substudy contains a Phase 2 part followed by a Phase 3 part. Participants will be randomized to one of two dose levels of BNT327 plus chemotherapy for the Phase 2 part of each substudy. After the analysis of the Phase 2 data (efficacy, safety, and exposure-response), an internal review committee (IRC) will decide whether participants will be treated wit...
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 982
- 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.
Key
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Have histologically or cytologically confirmed NSCLC with small-cell lung cancer histologic component.
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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.
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Have uncontrolled hypertension or poorly controlled diabetic conditions prior to study treatment.
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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.
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Participants with evidence of major coagulation disorders or other significant risks of hemorrhage.
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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
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Substudy A Phase 2 - BNT327 Dose 1 + Carboplatin + Pemetrexed BNT327 - Substudy A Phase 2 - BNT327 Dose 1 + Carboplatin + Pemetrexed Carboplatin - Substudy A Phase 2 - BNT327 Dose 1 + Carboplatin + Pemetrexed Pemetrexed - Substudy A Phase 2 - BNT327 Dose 2 + Carboplatin + Pemetrexed BNT327 - Substudy A Phase 2 - BNT327 Dose 2 + Carboplatin + Pemetrexed Carboplatin - Substudy A Phase 2 - BNT327 Dose 2 + Carboplatin + Pemetrexed Pemetrexed - Substudy A Phase 3 - BNT327 + Carboplatin + Pemetrexed BNT327 BNT327 selected dose for Phase 3 Substudy A Phase 3 - BNT327 + Carboplatin + Pemetrexed Carboplatin BNT327 selected dose for Phase 3 Substudy A Phase 3 - BNT327 + Carboplatin + Pemetrexed Pemetrexed BNT327 selected dose for Phase 3 Substudy A Phase 3 - Pembrolizumab + Carboplatin + Pemetrexed Pembrolizumab - Substudy A Phase 3 - Pembrolizumab + Carboplatin + Pemetrexed Carboplatin - Substudy A Phase 3 - Pembrolizumab + Carboplatin + Pemetrexed Pemetrexed - Substudy B Phase 2 - BNT327 Dose 1 + Carboplatin + Paclitaxel BNT327 - Substudy B Phase 2 - BNT327 Dose 1 + Carboplatin + Paclitaxel Carboplatin - Substudy B Phase 2 - BNT327 Dose 1 + Carboplatin + Paclitaxel Paclitaxel - Substudy B Phase 2 - BNT327 Dose 2 + Carboplatin + Paclitaxel BNT327 - Substudy B Phase 2 - BNT327 Dose 2 + Carboplatin + Paclitaxel Carboplatin - Substudy B Phase 2 - BNT327 Dose 2 + Carboplatin + Paclitaxel Paclitaxel - Substudy B Phase 3 - BNT327 + Carboplatin + Paclitaxel BNT327 BNT327 selected dose for Phase 3 Substudy B Phase 3 - BNT327 + Carboplatin + Paclitaxel Carboplatin BNT327 selected dose for Phase 3 Substudy B Phase 3 - BNT327 + Carboplatin + Paclitaxel Paclitaxel BNT327 selected dose for Phase 3 Substudy B Phase 3 - Pembrolizumab + Carboplatin + Paclitaxel Pembrolizumab - Substudy B Phase 3 - Pembrolizumab + Carboplatin + Paclitaxel Carboplatin - Substudy B Phase 3 - Pembrolizumab + Carboplatin + Paclitaxel Paclitaxel -
- Primary Outcome Measures
Name Time Method Phase 2 - 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 From the first dose of the investigational medicinal product (IMP) to the 90-day Follow-Up Visit For substudies A and B. AEs graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0 in the combination treatment regimen.
Phase 2 - Occurrence of dose interruption, reduction, and discontinuation of IMP due to TEAEs (including related TEAEs) From the first dose of IMP to the 90-day Follow-Up Visit For substudies A and B.
Phase 2 - Objective response rate (ORR) - unconfirmed Up to approximately 2 years For substudies A and B. ORR is defined as the proportion of participants in whom a complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\] based on the investigator's assessment) is observed as best overall response.
Phase 2 - Best percentage change from baseline in tumor size Up to approximately 2 years For substudies A and B. Based on investigator's tumor assessment according to RECIST 1.1.
Phase 3 - Progression free survival (PFS) assessed by blinded independent central review (BICR) Up to approximately 5 years For substudies A and B PFS defined as the time from randomization to first documented tumor progression (progressive disease per RECIST v1.1), or death from any cause, whichever occurs first.
Phase 3 - Overall survival (OS) Up to approximately 5 years For substudies A and B. OS defined as the time from randomization to death from any cause
- Secondary Outcome Measures
Name Time Method Phase 2 - ORR - confirmed Up to approximately 2 years For substudies A and B. ORR defined as the proportion of participants whom a CR or PR (per RECIST v1.1) is observed as best overall response with confirmation.
Phase 2 - Duration of Response (DOR) Up to approximately 2 years For substudies A and B. DOR defined as the time from first objective response (CR or PR 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.
Phase 2 - Disease Control Rate (DCR) Up to approximately 2 years For substudies A and B. DCR defined as the proportion of participants in whom a CR or PR or stable disease (per RECIST v1.1, stable disease assessed at least 6 weeks after randomization) is observed as best overall response.
Phase 3 - PFS assessed by investigator Up to approximately 5 years For substudies A and B. PFS defined as the time from randomization to first documented tumor progression (progressive disease per RECIST v1.1), or death from any cause, whichever occurs first.
Phase 3 - ORR assessed by BICR and by the investigator Up to approximately 2 years For substudies A and B. ORR defined as the proportion of participants in whom a CR or PR (per RECIST v1.1) is observed as best overall response with confirmation.
Phase 3 - DOR assessed by BICR and by the investigator Up to approximately 2 years For substudies A and B. DOR defined as the time from first objective response (CR or PR 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.
Phase 3 - DCR assessed by BICR and by the investigator Up to approximately 2 years For substudies A and B. DCR defined as the proportion of participants in whom a CR or PR or stable disease (per RECIST v1.1, stable disease assessed at least 6 weeks after randomization) is observed as best overall response.
Phase 3 - PFS rate as assessed by BICR At 6, 12, and 18 months For substudies A and B.
Phase 3 - PFS rate as assessed by investigator At 6, 12, and 18 months For substudies A and B.
Phase 3 - OS rate At 6, 12, 18, 24 months For substudies A and B.
Phase 3 - Change from baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-life-Core 30 Questionnaire (QLQ-C30) Up to approximately 5 years For substudies A and B. The EORTC QLQ-C30 is the most widely used cancer-specific, health related Quality-of-Life (QoL) instrument containing a total of 30 items and measures 5 functional scales (physical, role, emotional, cognitive, and social), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipa...
Phase 3 - Change from baseline in EORTC Lung Cancer-Specific QoL Questionnaire (QLC-LC29) Up to approximately 5 years For substudies A and B. The EORTC QLQ-LC29 is a disease-specific supplementary health related QoL questionnaire module to be employed in conjunction with the QLQ-C30. It comprises of 29 items and measures 5 multi-item scales (coughing, shortness of breath, side effects, tumor progression/existential issues, surgery-related symptoms) and 5 single items (cough...
Phase 3 - Change from baseline in Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) total score and domain score Up to approximately 5 years For substudies A and B. The NSCLC-SAQ is a 7-item patient reposted outcome (PRO) measure for use in adults to assess symptoms of advanced non-small cell lung cancer. It contains 5 domains and accompanying items that were identified as symptoms of non-small cell lung cancer: cough (1 item), pain (2), dyspnea (1), fatigue (2), and appetite (1). The (total) low...
Phase 3 - Occurrence of TEAEs including Grade ≥3, serious, and fatal TEAEs by relationship From the first dose of IMP to the 90-day Follow-Up Visit For substudies A and B. AEs graded according to CTCAE v5.0.
Phase 3 - Occurrence of dose interruption, reduction, and discontinuation of IMP due to TEAEs (including related TEAEs) From the first dose of IMP to the 90-day Follow-Up Visit For substudies A and B.