Safety, Effectiveness, and Pharmacokinetics of BNT327 in Combination With Chemotherapy and Other Investigational Agents for Lung Cancer
- Conditions
- Non-small Cell Lung Cancer
- 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 recommend whether participants will be treated with BNT327 at dose level 1 or 2 in the Phase 3 part of the substudies. After dose selection, the selected dose will be used for all participants in the study. For the Phase 3 part of both substudies, an independent data monitoring committee (IDMC) and a blinded Independent Central Review (BICR) will be established. The IDCM will provide independent review of the data during the study as needed and the BICR will review all available tumor assessment scans for all treated participants.
The planned study duration per study participant is up to 64 months.
Recruitment & Eligibility
- Status
- 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 epidermal growth factor receptor mutation or anaplastic lymphoma kinase (ALK) 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 performance status of 0 or 1.
- Adequate organ function.
Key
-
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.
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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 Carboplatin - Substudy A Phase 2 - BNT327 Dose 1 + Carboplatin + Pemetrexed Pemetrexed - 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 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 Carboplatin - Substudy B Phase 2 - BNT327 Dose 2 + Carboplatin + Paclitaxel BNT327 - 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 - Substudy A Phase 2 - BNT327 Dose 1 + Carboplatin + Pemetrexed BNT327 - Substudy A Phase 2 - BNT327 Dose 2 + Carboplatin + Pemetrexed BNT327 - Substudy A Phase 3 - BNT327 + Carboplatin + Pemetrexed BNT327 BNT327 selected dose for Phase 3
- 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) Up to approximately 2 years For substudies A and B. ORR is defined as the proportion of participants in whom a confirmed complete response (CR) or confirmed 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 v1.1.
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 - 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 confirmed CR or confirmed 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 Up to approximately 2 years For substudies A and B. ORR defined as the proportion of participants in whom a confirmed CR or confirmed PR (per RECIST v1.1) 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-score 30 Questionnaire (QLQ-C30) global health status/Quality-of-Life (QoL) score (Items 29 and 30) Up to approximately 5 years For substudies A and B. The EORTC QLQ-C30 is the most widely used cancer-specific, health related 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, constipation, diarrhea, and financial difficulties), and a global health status/QoL scale. All the scales and single-item measures range in score from 0 to 100 with a high scale score representing a higher response level (i.e., high score for global health status/QoL is high QoL: high score for symptom scale/item is high symptomatology or problems).
Phase 3 - Change from baseline in EORTC QLQ-C30 physical functioning Up to approximately 5 years For substudies A and B. The EORTC QLQ-C30 is the most widely used cancer-specific, health related 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, constipation, diarrhea, and financial difficulties), and a global health status/QoL scale. All the scales and single-item measures range in score from 0 to 100 with a high scale score representing a higher response level (i.e., high score for functional scale is high/healthy level of functioning).
Phase 3 - Change from baseline in coughing scale of the EORTC lung cancer-specific quality-of-life questionnaire (QLQ-LC29) Up to approximately 5 years For substudies A and B. The EORTC QLQ-LC29 is a disease-specific supplementary health-related quality-of-life (HRQoL) questionnaire module to be employed in conjunction with the QLQ-C30. It comprises 29 items and measures five multi-item scales (coughing, shortness of breath, side effects, tumor progression/existential issues, surgery-related symptoms) and five single items (coughing up blood, pain in chest, arm/shoulder and other parts of the body, and weight loss). All the scales and single-item measures range in score from 0 to 100 with a high score for the scales and single items representing a high level of symptomatology or problems.
Phase 3 - Change from baseline in shortness of breath scale of the EORTC QLQ-LC29 Up to approximately 5 years For substudies A and B. The EORTC QLQ-LC29 is a disease-specific supplementary health-related quality-of-life (HRQoL) questionnaire module to be employed in conjunction with the QLQ-C30. It comprises 29 items and measures five multi-item scales (coughing, shortness of breath, side effects, tumor progression/existential issues, surgery-related symptoms) and five single items (coughing up blood, pain in chest, arm/shoulder and other parts of the body, and weight loss). All the scales and single-item measures range in score from 0 to 100 with a high score for the scales and single items representing a high level of symptomatology or problems.
Phase 3 - Change from baseline in coughed up blood item of the EORTC QLQ-LC29 Up to approximately 5 years For substudies A and B. The EORTC QLQ-LC29 is a disease-specific supplementary health-related quality-of-life (HRQoL) questionnaire module to be employed in conjunction with the QLQ-C30. It comprises 29 items and measures five multi-item scales (coughing, shortness of breath, side effects, tumor progression/existential issues, surgery-related symptoms) and five single items (coughing up blood, pain in chest, arm/shoulder and other parts of the body, and weight loss). All the scales and single-item measures range in score from 0 to 100 with a high score for the scales and single items representing a high level of symptomatology or problems.
Phase 3 - Change from baseline in fatigue domain score scale of the Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) Up to approximately 5 years For substudies A and B. The NSCLC-SAQ is a 7-item patient-reported outcome measure for use in adults to assess symptoms of advanced non-small cell lung cancer. It contains five 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) lowest score possible is 0, and the highest (total) score possible is 20. Higher scores indicate more severe symptoms.
Phase 3 - Change from baseline in pain domain score of the NSCLC-SAQ Up to approximately 5 years For substudies A and B. The NSCLC-SAQ is a 7-item PRO measure for use in adults to assess symptoms of advanced non-small cell lung cancer. It contains five 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) lowest score possible is 0, and the highest (total) score possible is 20. Higher scores indicate more severe symptoms.
Phase 3 - Change from baseline in Functional Assessment of Cancer Therapy-General item 5 overall bother item (FACT-GP5). Up to approximately 5 years For substudies A and B. 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. The single-item GP5 ("I am bothered by side effects of treatment") is rated on a 5-point Likert scale ("not at all" to "very much") with a recall period of past 7 days.
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.
Related Research Topics
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Trial Locations
- Locations (65)
Alaska Oncology and Hematology, LLC
🇺🇸Anchorage, Alaska, United States
Clermont Oncology Center
🇺🇸Clermont, Florida, United States
Physicians Clinic of Iowa
🇺🇸Cedar Rapids, Iowa, United States
SSM Health Cancer Care - St. Clare
🇺🇸Fenton, Missouri, United States
Astera Cancer Care
🇺🇸East Brunswick, New Jersey, United States
Fletcher Hospital, Inc. dba AdventHealth Hendersonville
🇺🇸Hendersonville, North Carolina, United States
University of Tennessee Medical Center
🇺🇸Knoxville, Tennessee, United States
Baptist Cancer Center
🇺🇸Memphis, Tennessee, United States
Millennium Research and Clinical Development, LLC
🇺🇸Houston, Texas, United States
Cairns Hospital
🇦🇺Cairns, Australia
Scroll for more (55 remaining)Alaska Oncology and Hematology, LLC🇺🇸Anchorage, Alaska, United States