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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- BioNTech SE
- 入组人数
- 1,580
- 试验地点
- 365
- 主要终点
- Phase 2 - Occurrence of dose interruption, reduction, and discontinuation of IMP due to TEAEs (including related TEAEs)
研究概览
简要总结
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.
详细描述
Each substudy contains a Phase 2 part followed by a Phase 3 part. In the Phase 2 part, participants will be randomized to one of two dose levels of pumitamig (also known as BNT327, BMS-986545, or PM8002) plus chemotherapy (Arm 1 and Arm 2). In the Phase 3 part, participants will be randomized to pumitamig plus chemotherapy (Arm 3) or pembrolizumab plus chemotherapy (Arm 4). In China, additional participants will be enrolled into the Phase 2 part of each substudy to receive pumitamig plus chemotherapy (Arm 1A) to further evaluate the selected Phase 3 dose.
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 and will confirm the progression of disease, if applicable.
The planned study duration per study participant is up to 64 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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
- •Adequate organ function as defined in the protocol.
排除标准
- •Have histologically or cytologically confirmed NSCLC with small-cell lung cancer or neuroendocrine histologic 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 neoadjuvant/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).
- •Participants have superior vena cava syndrome or symptoms of spinal cord compression.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria apply.
研究组 & 干预措施
Substudy A Phase 2 (Arm 2) - Pumitamig Dose 2 + Carboplatin + Pemetrexed
干预措施: Pumitamig (Drug)
Substudy A Phase 2 (Arm 1A - China only) - Pumitamig Dose 3 + Carboplatin + Pemetrexed
干预措施: Pumitamig (Drug)
Substudy A Phase 3 (Arm 3) - Pumitamig Dose 3 + Carboplatin + Pemetrexed
干预措施: Pumitamig (Drug)
Substudy B Phase 2 (Arm 1) - Pumitamig Dose 1 + Carboplatin + Paclitaxel
干预措施: Pumitamig (Drug)
Substudy A Phase 2 (Arm 1) - Pumitamig Dose 1 + Carboplatin + Pemetrexed
干预措施: Pemetrexed (Drug)
Substudy A Phase 2 (Arm 2) - Pumitamig Dose 2 + Carboplatin + Pemetrexed
干预措施: Pemetrexed (Drug)
Substudy A Phase 2 (Arm 1A - China only) - Pumitamig Dose 3 + Carboplatin + Pemetrexed
干预措施: Pemetrexed (Drug)
Substudy A Phase 3 (Arm 3) - Pumitamig Dose 3 + Carboplatin + Pemetrexed
干预措施: Carboplatin (Drug)
Substudy B Phase 2 (Arm 1) - Pumitamig Dose 1 + Carboplatin + Paclitaxel
干预措施: Carboplatin (Drug)
Substudy B Phase 2 (Arm 1) - Pumitamig Dose 1 + Carboplatin + Paclitaxel
干预措施: Paclitaxel (Drug)
Substudy B Phase 2 (Arm 1A, China only) - Pumitamig Dose 3 + Carboplatin + Paclitaxel
干预措施: Paclitaxel (Drug)
Substudy A Phase 3 (Arm 3) - Pumitamig Dose 3 + Carboplatin + Pemetrexed
干预措施: Pemetrexed (Drug)
Substudy A Phase 3 (Arm 4) - Pembrolizumab + Carboplatin + Pemetrexed
干预措施: Pemetrexed (Drug)
Substudy B Phase 2 (Arm 2) - Pumitamig Dose 2 + Carboplatin + Paclitaxel
干预措施: Pumitamig (Drug)
Substudy B Phase 2 (Arm 2) - Pumitamig Dose 2 + Carboplatin + Paclitaxel
干预措施: Carboplatin (Drug)
Substudy B Phase 2 (Arm 1A, China only) - Pumitamig Dose 3 + Carboplatin + Paclitaxel
干预措施: Pumitamig (Drug)
Substudy B Phase 2 (Arm 1A, China only) - Pumitamig Dose 3 + Carboplatin + Paclitaxel
干预措施: Carboplatin (Drug)
Substudy B Phase 3 (Arm 3) - Pumitamig Dose 3 + Carboplatin + Paclitaxel
干预措施: Paclitaxel (Drug)
Substudy B Phase 3 (Arm 4) - Pembrolizumab + Carboplatin + Paclitaxel
干预措施: Pembrolizumab (Drug)
Substudy B Phase 3 (Arm 4) - Pembrolizumab + Carboplatin + Paclitaxel
干预措施: Carboplatin (Drug)
Substudy A Phase 3 (Arm 4) - Pembrolizumab + Carboplatin + Pemetrexed
干预措施: Pembrolizumab (Drug)
Substudy A Phase 2 (Arm 2) - Pumitamig Dose 2 + Carboplatin + Pemetrexed
干预措施: Carboplatin (Drug)
Substudy A Phase 2 (Arm 1) - Pumitamig Dose 1 + Carboplatin + Pemetrexed
干预措施: Pumitamig (Drug)
Substudy B Phase 3 (Arm 3) - Pumitamig Dose 3 + Carboplatin + Paclitaxel
干预措施: Pumitamig (Drug)
Substudy B Phase 3 (Arm 3) - Pumitamig Dose 3 + Carboplatin + Paclitaxel
干预措施: Carboplatin (Drug)
Substudy A Phase 2 (Arm 1A - China only) - Pumitamig Dose 3 + Carboplatin + Pemetrexed
干预措施: Carboplatin (Drug)
Substudy B Phase 2 (Arm 2) - Pumitamig Dose 2 + Carboplatin + Paclitaxel
干预措施: Paclitaxel (Drug)
Substudy B Phase 3 (Arm 4) - Pembrolizumab + Carboplatin + Paclitaxel
干预措施: Paclitaxel (Drug)
Substudy A Phase 2 (Arm 1) - Pumitamig Dose 1 + Carboplatin + Pemetrexed
干预措施: Carboplatin (Drug)
Substudy A Phase 3 (Arm 4) - Pembrolizumab + Carboplatin + Pemetrexed
干预措施: Carboplatin (Drug)
结局指标
主要结局
Phase 2 - Occurrence of dose interruption, reduction, and discontinuation of IMP due to TEAEs (including related TEAEs)
时间窗: From the first dose of IMP to the 90-day Follow-Up Visit
For substudies A and B.
Phase 2 - Objective response rate (ORR)
时间窗: 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
时间窗: 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 BICR
时间窗: 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 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
时间窗: 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)
时间窗: From the first dose of IMP to the 90-day Follow-Up Visit
For substudies A and B.
Phase 2 - Objective response rate (ORR)
时间窗: 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
时间窗: Up to approximately 2 years
For substudies A and B. Based on investigator's tumor assessment according to RECIST v1.1.
次要结局
- Phase 2 - Duration of Response (DOR)(Up to approximately 2 years)
- Phase 2 - Disease Control Rate (DCR)(Up to approximately 2 years)
- Phase 3 - PFS assessed by investigator(Up to approximately 5 years)
- Phase 3 - ORR(Up to approximately 2 years)
- Phase 3 - PFS rate as assessed by BICR(At 6, 12, and 18 months)
- 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)
- 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)
- Phase 3 - Change from baseline in coughed up blood item of the EORTC QLQ-LC29(Up to approximately 5 years)
- 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)
- 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)
- Phase 3 - Change from baseline in EORTC QLQ-C30 physical functioning(Up to approximately 5 years)
- 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)
- Phase 3 - Change from baseline in pain domain score of the NSCLC-SAQ(Up to approximately 5 years)
- Phase 3 - Change from baseline in Functional Assessment of Cancer Therapy-General item 5 overall bother item (FACT-GP5)(Up to approximately 5 years)
- Phase 3 - PFS rate as assessed by BICR(At 6, 12, and 18 months)
- Phase 3 - PFS rate as assessed by investigator(At 6, 12, and 18 months)
- Phase 3 - OS rate(At 6, 12, 18, 24 months)
- Phase 3 - Overall survival (OS)(Up to approximately 5 years)
- Phase 2 - Duration of Response (DOR)(Up to approximately 2 years)
- Phase 2 - Disease Control Rate (DCR)(Up to approximately 2 years)
- Phase 3 - PFS assessed by investigator(Up to approximately 5 years)
- Phase 3 - ORR(Up to approximately 2 years)
- 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)
- Phase 3 - Change from baseline in EORTC QLQ-C30 physical functioning(Up to approximately 5 years)
- 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)
- Phase 3 - Change from baseline in shortness of breath scale of the EORTC QLQ-LC29(Up to approximately 5 years)
- Phase 3 - Change from baseline in coughed up blood item of the EORTC QLQ-LC29(Up to approximately 5 years)
- 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)
- Phase 3 - Change from baseline in pain domain score of the NSCLC-SAQ(Up to approximately 5 years)
- Phase 3 - Change from baseline in Functional Assessment of Cancer Therapy-General item 5 overall bother item (FACT-GP5).(Up to approximately 5 years)
- 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)
- 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)