Non-small Cell Lung Cancer
Conditions
Keywords
First-line treatment, Combination with chemotherapy, Combination with other investigational agents, Bispecific antibody, Programmed death-ligand 1 (PD-L1), Vascular endothelial growth factor (VEGF) A, Immunotherapy, Programmed Death-1 monoclonal antibodies
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 pumitamig (BNT327) plus chemotherapy for the Phase 2 part of each substudy. 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 IDMC 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.
Interventions
DRUGPumitamig
Intravenous infusion
DRUGPembrolizumab
Intravenous infusion
DRUGCarboplatin
Intravenous infusion
DRUGPemetrexed
Intravenous infusion
DRUGPaclitaxel
Intravenous infusion
Sponsors
BioNTech SE
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Have systemic treatment naive, 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, 9th edition. * 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
Exclusion criteria
* Have histologically or cytologically confirmed NSCLC with small-cell lung cancer histologic or neuroendocrine component. * Have received any of the following therapies or drugs within the noted time intervals prior to study treatment: * Previous chemotherapy (platinum-based) or PD(L)-1 for treating NSCLC in either neo-adjuvant/adjuvant or locally advanced/metastatic setting. * Participants who received prior treatment with anti-VEGF monoclonal antibody, or 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 uncontrolled hypertension or poorly controlled diabetic conditions prior to study treatment. * Have a serious or non-healing wound, or (incompletely healed) 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 or esophageal and gastric varices. 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 significant risk of hemorrhage (per investigator clinical judgment). * Have superior vena cava syndrome or symptoms of spinal cord compression. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
Countries
Australia, Belgium, China, France, Germany, Italy, Japan, Poland, Romania, South Korea, Spain, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTBioNTech clinical trials patient information
STUDY_DIRECTORBioNTech Responsible Person
BioNTech SE
Outcome results
None listed