A Phase 2 Platform Study Evaluating the Safety and Efficacy of Novel Treatment Combinations in Patients With Lung Cancer (VELOCITY-Lung)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 192
- 试验地点
- 152
- 主要终点
- Substudies 01 and 02: Objective Response Rate (ORR) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
研究概览
简要总结
The goal of this platform clinical trial is to test how well novel treatment combinations work in participants with lung cancer. Substudy-01 will compare the different novel combinations versus standard of care in participants with metastatic (cancer that has spread) non-small-cell lung cancer (NSCLC) who have not been treated before. Substudy-02 will compare the different novel combination versus standard of care in participants with cancer that has progressed after receiving previous treatment for metastatic NSCLC. Substudy-03 will compare the different novel combinations versus standard of care in participants with resectable stage II-III NSCLC.
The primary objectives of this study are:
Substudy-01 and Substudy-02: To evaluate the objective response rate (ORR) assessed per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
Substudy-03: To evaluate the efficacy of treatment combinations based on complete pathological response (pCR) rate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •All Substudies:
- •Histologically or cytologically documented non-small-cell lung cancer (NSCLC).
- •No known actionable genomic alterations for which targeted therapies are available.
- •Eastern cooperative oncology group (ECOG) performance status score of 0 or
- •Measurable disease per response evaluation criteria in solid tumors.
- •Adequate hematologic and end-organ function.
- •Individuals of childbearing potential who engage in heterosexual intercourse must agree to use specified method(s) of contraception.
- •Substudy 01: All Experimental arms
- •Stage IV NSCLC.
- •For individuals with nonsquamous histology: Epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) alteration negative.
- •PD-L1 status by central confirmation.
- •No prior systemic treatment for metastatic NSCLC.
- •Substudy 02: All Experimental arms
- •Stage IV NSCLC.
- •In individuals with nonsquamous histology and actionable EGFR, ALK, or other known genomic alterations must have received treatment with at least 1 targeted therapy to the appropriate genomic alteration.
- •Substudy 03: All Experimental arms
- •Previously untreated individuals with resectable (Stage II, IIIA, IIIB (T[3-4]N2) NSCLC (per American Joint Committee on Cancer (AJCC) Edition 8).
- •Planned surgery must comprise of lobectomy, sleeve lobectomy, or bi-lobectomy.
- •PD-L1 status by central confirmation.
- •For individuals with nonsquamous histology: Epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) alteration negative.
排除标准
- •All Substudies:
- •Mixed small-cell lung cancer and NSCLC histology.
- •Active second malignancy.
- •Active autoimmune disease.
- •History of or current non-infectious pneumonitis/interstitial lung disease.
- •Active serious infection within 4 weeks prior to study treatment.
- •Substudy 01 and 02
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Received previous anticancer therapy within 4 weeks prior to enrollment.
- •Substudy 03: All Experimental arms
- •NSCLC previously treated with systemic therapy or radiotherapy.
- •Received prior treatment with any anti-PD-(L)-1 or other immune checkpoint inhibitors (CPIs).
- •Note: Other protocol defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Substudy 01: ZIM + Platinum Based Chemotherapy
Expansion Stage Only: Participants will receive ZIM plus any one of the chemotherapy (choice of chemotherapy is dependent on histology).
Platinum Based Chemotherapy will be cisplatin or carboplatin and pemetrexed (non-squamous histology) or carboplatin, paclitaxel and nabpaclitaxel (squamous histology).
干预措施: Pemetrexed (Drug)
Substudy 02: Either Docetaxel or SG (Monotherapy Only)
Participants will receive either Docetaxel or SG until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met.
干预措施: Sacituzumab govitecan-hziy (SG) (Drug)
Substudy 02: SG + ZIM + ETRUMA
Participants will receive SG, ZIM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met.
干预措施: Sacituzumab govitecan-hziy (SG) (Drug)
Substudy 02: Either Docetaxel or SG (Monotherapy Only)
Participants will receive either Docetaxel or SG until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met.
干预措施: Docetaxel (Drug)
Substudy 03 - ZIM + DOM + Platinum-based Chemotherapy
Participants will receive ZIM plus DOM and any one of the chemotherapy (choice of chemotherapy is dependent on histology).
Platinum Based Chemotherapy will be carboplatin and pemetrexed (non-squamous histology) or carboplatin and paclitaxel (squamous histology).
干预措施: Pemetrexed (Drug)
Substudy 01: Zimberelimab (ZIM) + Sacituzumab govitecan-hziy (SG)
Participants will receive ZIM and SG until disease progression (PD), unacceptable toxicity, or protocol specified discontinuation criteria are met.
干预措施: Sacituzumab govitecan-hziy (SG) (Drug)
Substudy 01: Zimberelimab (ZIM) + Sacituzumab govitecan-hziy (SG) + Domvanalimab (DOM)
Participants will receive ZIM, SG and DOM until disease progression (PD), unacceptable toxicity, or protocol specified discontinuation criteria are met.
干预措施: Domvanalimab (DOM) (Drug)
Substudy 01: Zimberelimab (ZIM) + Sacituzumab govitecan-hziy (SG) + Domvanalimab (DOM)
Participants will receive ZIM, SG and DOM until disease progression (PD), unacceptable toxicity, or protocol specified discontinuation criteria are met.
干预措施: Sacituzumab govitecan-hziy (SG) (Drug)
Substudy 01: ZIM + DOM + Etrumadenant (ETRUMA)
Participants will receive ZIM, DOM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met.
干预措施: Domvanalimab (DOM) (Drug)
Substudy 03 - ZIM + DOM + Platinum-based Chemotherapy
Participants will receive ZIM plus DOM and any one of the chemotherapy (choice of chemotherapy is dependent on histology).
Platinum Based Chemotherapy will be carboplatin and pemetrexed (non-squamous histology) or carboplatin and paclitaxel (squamous histology).
干预措施: Domvanalimab (DOM) (Drug)
Substudy 02: SG + ZIM + ETRUMA
Participants will receive SG, ZIM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met.
干预措施: Etrumadenant (ETRUMA) (Drug)
Substudy 03 - ZIM + DOM + Platinum-based Chemotherapy
Participants will receive ZIM plus DOM and any one of the chemotherapy (choice of chemotherapy is dependent on histology).
Platinum Based Chemotherapy will be carboplatin and pemetrexed (non-squamous histology) or carboplatin and paclitaxel (squamous histology).
干预措施: Zimberelimab (ZIM) (Drug)
Substudy 03 - ZIM + Platinum-based Chemotherapy
Participants will receive ZIM plus any one of the chemotherapy (choice of chemotherapy is dependent on histology).
Platinum Based Chemotherapy will be carboplatin and pemetrexed (non-squamous histology) or carboplatin and paclitaxel (squamous histology).
干预措施: Zimberelimab (ZIM) (Drug)
Substudy 01: ZIM + DOM + Etrumadenant (ETRUMA)
Participants will receive ZIM, DOM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met.
干预措施: Etrumadenant (ETRUMA) (Drug)
Substudy 01: Zimberelimab (ZIM) + Sacituzumab govitecan-hziy (SG) + Domvanalimab (DOM)
Participants will receive ZIM, SG and DOM until disease progression (PD), unacceptable toxicity, or protocol specified discontinuation criteria are met.
干预措施: Zimberelimab (ZIM) (Drug)
Substudy 01: ZIM + DOM + Etrumadenant (ETRUMA)
Participants will receive ZIM, DOM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met.
干预措施: Zimberelimab (ZIM) (Drug)
Substudy 01: ZIM + ETRUMA
Participants will receive ZIM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met.
干预措施: Zimberelimab (ZIM) (Drug)
Substudy 01: ZIM + ETRUMA
Participants will receive ZIM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met.
干预措施: Etrumadenant (ETRUMA) (Drug)
Substudy 01: Zimberelimab (ZIM) + Sacituzumab govitecan-hziy (SG)
Participants will receive ZIM and SG until disease progression (PD), unacceptable toxicity, or protocol specified discontinuation criteria are met.
干预措施: Zimberelimab (ZIM) (Drug)
Substudy 01: ZIM + Platinum Based Chemotherapy
Expansion Stage Only: Participants will receive ZIM plus any one of the chemotherapy (choice of chemotherapy is dependent on histology).
Platinum Based Chemotherapy will be cisplatin or carboplatin and pemetrexed (non-squamous histology) or carboplatin, paclitaxel and nabpaclitaxel (squamous histology).
干预措施: Zimberelimab (ZIM) (Drug)
Substudy 01: ZIM + Platinum Based Chemotherapy
Expansion Stage Only: Participants will receive ZIM plus any one of the chemotherapy (choice of chemotherapy is dependent on histology).
Platinum Based Chemotherapy will be cisplatin or carboplatin and pemetrexed (non-squamous histology) or carboplatin, paclitaxel and nabpaclitaxel (squamous histology).
干预措施: Nab-paclitaxel (Drug)
Substudy 02: SG + ZIM + ETRUMA
Participants will receive SG, ZIM and ETRUMA until PD, unacceptable toxicity, or protocol specified discontinuation criteria are met.
干预措施: Zimberelimab (ZIM) (Drug)
Substudy 01: ZIM + Platinum Based Chemotherapy
Expansion Stage Only: Participants will receive ZIM plus any one of the chemotherapy (choice of chemotherapy is dependent on histology).
Platinum Based Chemotherapy will be cisplatin or carboplatin and pemetrexed (non-squamous histology) or carboplatin, paclitaxel and nabpaclitaxel (squamous histology).
干预措施: Carboplatin (Drug)
Substudy 01: ZIM + Platinum Based Chemotherapy
Expansion Stage Only: Participants will receive ZIM plus any one of the chemotherapy (choice of chemotherapy is dependent on histology).
Platinum Based Chemotherapy will be cisplatin or carboplatin and pemetrexed (non-squamous histology) or carboplatin, paclitaxel and nabpaclitaxel (squamous histology).
干预措施: Cisplatin (Drug)
Substudy 01: ZIM + Platinum Based Chemotherapy
Expansion Stage Only: Participants will receive ZIM plus any one of the chemotherapy (choice of chemotherapy is dependent on histology).
Platinum Based Chemotherapy will be cisplatin or carboplatin and pemetrexed (non-squamous histology) or carboplatin, paclitaxel and nabpaclitaxel (squamous histology).
干预措施: Paclitaxel (Drug)
Substudy 03 - ZIM + DOM + Platinum-based Chemotherapy
Participants will receive ZIM plus DOM and any one of the chemotherapy (choice of chemotherapy is dependent on histology).
Platinum Based Chemotherapy will be carboplatin and pemetrexed (non-squamous histology) or carboplatin and paclitaxel (squamous histology).
干预措施: Carboplatin (Drug)
Substudy 03 - ZIM + DOM + Platinum-based Chemotherapy
Participants will receive ZIM plus DOM and any one of the chemotherapy (choice of chemotherapy is dependent on histology).
Platinum Based Chemotherapy will be carboplatin and pemetrexed (non-squamous histology) or carboplatin and paclitaxel (squamous histology).
干预措施: Paclitaxel (Drug)
Substudy 03 - ZIM + Platinum-based Chemotherapy
Participants will receive ZIM plus any one of the chemotherapy (choice of chemotherapy is dependent on histology).
Platinum Based Chemotherapy will be carboplatin and pemetrexed (non-squamous histology) or carboplatin and paclitaxel (squamous histology).
干预措施: Carboplatin (Drug)
Substudy 03 - ZIM + Platinum-based Chemotherapy
Participants will receive ZIM plus any one of the chemotherapy (choice of chemotherapy is dependent on histology).
Platinum Based Chemotherapy will be carboplatin and pemetrexed (non-squamous histology) or carboplatin and paclitaxel (squamous histology).
干预措施: Pemetrexed (Drug)
Substudy 03 - ZIM + Platinum-based Chemotherapy
Participants will receive ZIM plus any one of the chemotherapy (choice of chemotherapy is dependent on histology).
Platinum Based Chemotherapy will be carboplatin and pemetrexed (non-squamous histology) or carboplatin and paclitaxel (squamous histology).
干预措施: Paclitaxel (Drug)
Substudy 03: Nivolumab + Platinum-based Chemotherapy
Participants will receive nivolumab plus any one of the chemotherapy (choice of chemotherapy is dependent on histology).
Platinum Based Chemotherapy will be carboplatin and pemetrexed (non-squamous histology) or carboplatin and paclitaxel (squamous histology).
干预措施: Carboplatin (Drug)
Substudy 03: Nivolumab + Platinum-based Chemotherapy
Participants will receive nivolumab plus any one of the chemotherapy (choice of chemotherapy is dependent on histology).
Platinum Based Chemotherapy will be carboplatin and pemetrexed (non-squamous histology) or carboplatin and paclitaxel (squamous histology).
干预措施: Pemetrexed (Drug)
Substudy 03: Nivolumab + Platinum-based Chemotherapy
Participants will receive nivolumab plus any one of the chemotherapy (choice of chemotherapy is dependent on histology).
Platinum Based Chemotherapy will be carboplatin and pemetrexed (non-squamous histology) or carboplatin and paclitaxel (squamous histology).
干预措施: Paclitaxel (Drug)
Substudy 03: Nivolumab + Platinum-based Chemotherapy
Participants will receive nivolumab plus any one of the chemotherapy (choice of chemotherapy is dependent on histology).
Platinum Based Chemotherapy will be carboplatin and pemetrexed (non-squamous histology) or carboplatin and paclitaxel (squamous histology).
干预措施: Nivolumab (Drug)
结局指标
主要结局
Substudies 01 and 02: Objective Response Rate (ORR) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
时间窗: Up to 5 years
ORR is defined as the proportion of participants achieving a complete response (CR) or partial response (PR) as confirmed at least 4 weeks after the first detection of response.
Substudy 03: Complete Pathological Response (pCR) Rate
时间窗: Up to 5 years
pCR is defined as the percentage of participants having an absence of residual invasive cancer in resected lung specimens and lymph nodes as assessed by local pathology review.
次要结局
- Substudies 01 and 02: Progression-free Survival (PFS) According to RECIST Version 1.1(Up to 5 years)
- Substudies 01 and 02: Duration of response (DOR) According to RECIST Version 1.1(Up to 5 years)
- All Substudies: Overall survival (OS)(Up to 5 years)
- Substudy 03: Event-Free Survival (EFS)(Up to 5 years)
- Substudy 03: Major Pathological Response (MPR) Rate(Up to 5 years)
- All Substudies: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) and Related TEAEs(First dose date up to 24 months plus 100 days)
- All Substudies: Percentage of Participants Experiencing Clinical Laboratory Abnormalities(First dose date up to 24 months plus 100 days)