A Phase 2 Open-label, Multicenter, Randomized, Multidrug Platform Study of Neoadjuvant Durvalumab Alone or in Combination With Novel Agents in Subjects With Resectable, Early-stage (I [> 2 cm] to IIIA) Non-small Cell Lung Cancer (NeoCOAST)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Major Pathological Response Rate
研究概览
简要总结
Study D9108C00002 (NeoCOAST) is a platform study assessing the effectiveness and safety of neoadjuvant durvalumab alone or in combination with novel agents in participants with resectable, early-stage (Stage I [>2cm] to IIIA) non-small cell lung cancer (NSCLC).
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 102 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cytologically and/or histologically-documented NSCLC
- •Stage I (> 2 cm) to IIIA (for participants with N2 disease, only those with 1 single nodal station ≤ 3 cm are eligible) NSCLC according to the 8th edition of American Joint Committee on Cancer staging classification
- •Amenable to complete surgical resection
- •Have not received any other therapy for this condition
- •Predicted forced expiratory volume in one second (FEV1) ≥ 50%
- •Predicted diffusing capacity of the lungs for carbon monoxide (DLCO) ≥ 50%
- •ECOG 0 or 1
- •Adequate organ function
排除标准
- •Participants with small-cell lung cancer or mixed small-cell lung cancer
- •Participants who require or may require pneumonectomy
- •Prior treatment with programmed cell death ligand-1 (PD-L1), PD-L1, or cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors
- •Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug.
- •Active or prior documented autoimmune or inflammatory disorders. The following are exceptions to this criterion:
- •Participants with vitiligo or alopecia
- •Participants with hypothyroidism on hormone replacement
- •Any chronic skin condition that does not require systemic therapy
- •Participants without active disease in the last 5 years may be included but only after consultation with the study physician
- •Participants with celiac disease controlled by diet alone
- •Pregnant or breast-feeding female
- •Major surgical procedure within prior 30 days
- •History of active primary immunodeficiency
- •Active infection including tuberculosis, hepatitis B, hepatitis C, or HIV
- •QTc interval (QTc) ≥ 470 ms
- •Uncontrolled intercurrent illness that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the participant to give written informed consent
- •Receipt of live attenuated vaccination within 30 days prior to study entry
- •History of another primary malignancy except for:
- •Curative-treated malignancy with no known active disease > 2 years before enrollment on the study
- •Curative-treated non-melanoma skin cancer and/or carcinoma in-situ
研究组 & 干预措施
Durvalumab 1500 mg
Participants will receive durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection will be planned between Day 29 and Day 42. After surgical resection, participants will be followed up to Day 105 (starting from Week 1 Day 1).
干预措施: Durvalumab (Drug)
Durvalumab 1500 mg + Oleclumab 3000 mg
Participants will receive durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection will be planned between Day 29 and Day 42. After surgical resection, participants will be followed up to Day 105 (starting from Week 1 Day 1).
干预措施: Durvalumab (Drug)
Durvalumab 1500 mg + Oleclumab 3000 mg
Participants will receive durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection will be planned between Day 29 and Day 42. After surgical resection, participants will be followed up to Day 105 (starting from Week 1 Day 1).
干预措施: Oleclumab (Combination Product)
Durvalumab 1500 mg + Monalizumab 750 mg
Participants will receive durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection will be planned between Day 29 and Day 42. After surgical resection, participants will be followed up to Day 105 (starting from Week 1 Day 1).
干预措施: Durvalumab (Drug)
Durvalumab 1500 mg + Monalizumab 750 mg
Participants will receive durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection will be planned between Day 29 and Day 42. After surgical resection, participants will be followed up to Day 105 (starting from Week 1 Day 1).
干预措施: Monalizumab (Combination Product)
Durvalumab 1500 mg + Danvatirsen 200 mg
Participants will receive danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection will be planned between Day 29 and Day 42. After surgical resection, participants will be followed up to Day 105 (starting from Week 1 Day 1).
干预措施: Durvalumab (Drug)
Durvalumab 1500 mg + Danvatirsen 200 mg
Participants will receive danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection will be planned between Day 29 and Day 42. After surgical resection, participants will be followed up to Day 105 (starting from Week 1 Day 1).
干预措施: Danvatirsen (Combination Product)
结局指标
主要结局
Major Pathological Response Rate
时间窗: Day 1 through Day 42
Major pathological response rate is defined as percentage of participants with \<=10% residual viable tumor cells in the resected specimen.
次要结局
- Pathological Complete Response (pCR) Rate(Day 1 through Day 42)
- Feasibility to Surgery(Day 29 to Day 42 after Week 1 Day 1)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)(From Day 1 through Day 105)
- Number of Participants With Grade 3 or Grade 4 Clinical Laboratory Toxicities(From Day 1 through Day 105)
- Number of Participants With Abnormal Vital Signs Reported as TEAEs(From Day 1 through Day 105)