The Study of NC318 Alone or in Combination With Pembrolizumab in Patients With Advanced Non-small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 159
- 试验地点
- 1
- 主要终点
- Number of participants on Arm 1b with treatment related adverse events as assessed by CTCAE v5
研究概览
简要总结
This is a phase 2 study to investigate NC318 alone or in combination with Pembrolizumab in patients with advanced non-small cell lung cancer.
详细描述
This is a non-randomized, three-arm trial.
Arm 1a and 1b will enroll patients with advanced NSCLC regardless of tumor PD-L1 expression who have experienced disease progression on or after PD-1 axis inhibitor therapy, given alone or in combination with other systemic anti-cancer therapy. Patients will be assigned to arm 1a or 1b at the discretion of the treating physician. Patients on arm 1a will receive NC318 alone; those on arm 1b, combination therapy with NC318 and pembrolizumab.
Arm 1a will be based on a Simon two-stage minimax design. In the first stage, 18 patients will be accrued. If tumor response per RECIST v1.1 is achieved in 2 or fewer patients, arm 1a will be closed to further enrollment. If tumor response is demonstrated in 3 or more patients, then 25 additional patients will be accrued (stage 2), for a total of 43 patients.
Arm 1a and 1b will start with a safety run-in portion consisting of 6 patients (see 4.1.1). If deemed safe, each arm will continue to accrue and follow the Simon two-stage design outlined above. Patients in the run-in portion will be included in stage 1 of the Simon two-stage design.
Arm 2 will enroll patients with advanced NSCLC and tumor PD-L1 expression less than 50% who are naïve to PD-1 axis inhibitor therapy. Patients on arm 2 will receive combination therapy with NC318 and pembrolizumab. Arm 2 will also start with a safety run-in portion identical to that of arms 1a and 1b (see 4.1.1). If deemed safe, accrual will continue following a Simon two-stage minimax design. In the first stage, 19 patients will be accrued. If tumor response per RECIST v1.1 is achieved in 3 or fewer patients, arm 2 will be closed to further enrollment. If tumor response is demonstrated in 4 or more patients, then 36 additional patients will be accrued (stage 2), for a total of 54 patients. Patients in the run-in portion will be included in stage 1 of the Simon two-stage design.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Histologically or cytologically documented, locally advanced or metastatic (i.e., Stage IIIB not eligible for definitive chemoradiotherapy, Stage IV, or recurrent) NSCLC (per the American Joint Committee /AJCC staging system)
- •ECOG performance status of 0 to 1
- •Measurable disease per RECIST v1.1 criteria
- •Arm 1a, and 1b and 1c: Prior PD-1 axis inhibitor therapy (anti-PD-1 or anti-PD-L1, e.g. nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab) either alone or in combination with other systemic agents, with documented progressive disease.
- •Arm 2a: PD-L1 expression of less than 50 percent (PD-1 axis inhibitor therapy naïve)
- •Patients with NSCLC known to harbor an ALK rearrangement, ROS1 rearrangement, EGFR mutation or BRAF mutation known to be sensitive to FDA approved tyrosine kinase inhibitors (TKI), are only eligible after experiencing disease progression (during or after treatment) or intolerance to respective TKI:
- •Patients with TKI treated EGFR mutant NSCLC harboring the secondary EGFR T790M tumor must have received prior osimertinib.
- •Patients with crizotinib treated ALK rearranged NSCLC must have received a next generation ALK inhibitor (e.g. ceritinib, alectinib, brigatinib or lorlatinib).
- •At least one tumor amenable to incisional, excisional, core or forceps (transbronchial) biopsy. Patients must be willing to undergo a tumor biopsy before starting trial therapy and at the time of disease progression.
- •Adequate hematologic and end-organ function
排除标准
- •Subjects must not have a history of life-threatening toxicity related to prior anti-PD-1 axis therapy:
- •a. Subjects with history of anti-PD-1 axis therapy toxicities that are unlikely to recur with standard countermeasures (e.g., hormone replacement after adrenal crisis) are eligible.
- •Symptomatic or untreated CNS metastases. Patients with a history of treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria:
- •No evidence of interim progression between the completion of CNS-directed therapy and the start of trial therapy
- •No ongoing requirement for dexamethasone as therapy for CNS disease; anticonvulsants at a stable dose are allowed.
- •Completed stereotactic radiosurgery at least 1 week prior to initiation of trial therapyCycle 1, Day 1 or whole-brain radiation at least 2 weeks prior to initiation of trial therapyCycle 1, Day
- •History of leptomeningeal carcinomatosis
- •Prior palliative radiotherapy outside the CNS within 2 weeks of the first dose of study drug
- •Treatment with systemic immunosuppressive medications (including but not limited to, dexamethasone at doses > 2 mg daily (or equivalent dose of other corticosteroids), cyclophosphamide, tacrolimus, sirolimus, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor [anti-TNF] agents) within 2 weeks prior to initiating trial therapy. (Inhaled or topically applied steroids, and acute and chronic standard-dose NSAIDs are permitted. Replacement steroids are also permitted). Prophylactic corticosteroids prior to imaging with intravenous contrast are allowed per institutional guidelines, without need for delay of 2 weeks. Arm 2a: No prior PD-1 axis inhibitor therapy
研究组 & 干预措施
Arm 1b - NC318 and Pembrolizumab
At the discretion of the treating physician, advanced NSCLC patients on arm 1b will receive combination therapy with NC318 and pembrolizumab.
干预措施: NC318 400 mg (Drug)
Arm 1c - NC318 and Pembrolizumab
At the discretion of the treating physician, advanced NSCLC patients on arm 1b will receive combination therapy with NC318 and pembrolizumab.
干预措施: NC318 800 mg (Drug)
Arm 2a (naïve to PD-1 axis inhibitor)- NC318 and Pembrolizumab
Arm 2a will enroll patients with advanced NSCLC who are naïve to PD-1 axis inhibitor therapy to receive combination therapy with NC318 and pembrolizumab.
干预措施: NC318 800 mg (Drug)
Arm 1a - NC318 only
At the discretion of the treating physician, advanced NSCLC patients on arm 1a will receive NC318 alone.
干预措施: NC318 800 mg (Drug)
Arm 2 (naïve to PD-1 axis inhibitor)- NC318 and Pembrolizumab
Arm 2 will enroll patients with advanced NSCLC who are naïve to PD-1 axis inhibitor therapy to receive therapy with NC318 in combination with pembrolizumab.
干预措施: NC318 400 mg (Drug)
Arm 1b - NC318 and Pembrolizumab
At the discretion of the treating physician, advanced NSCLC patients on arm 1b will receive combination therapy with NC318 and pembrolizumab.
干预措施: Pembrolizumab (Drug)
Arm 2 (naïve to PD-1 axis inhibitor)- NC318 and Pembrolizumab
Arm 2 will enroll patients with advanced NSCLC who are naïve to PD-1 axis inhibitor therapy to receive therapy with NC318 in combination with pembrolizumab.
干预措施: Pembrolizumab (Drug)
Arm 2a (naïve to PD-1 axis inhibitor)- NC318 and Pembrolizumab
Arm 2a will enroll patients with advanced NSCLC who are naïve to PD-1 axis inhibitor therapy to receive combination therapy with NC318 and pembrolizumab.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Number of participants on Arm 1b with treatment related adverse events as assessed by CTCAE v5
时间窗: Safety run in of 6 weeks
To determine the safety of NC318 when administered in combination with pembrolizumab in arm 1b
Number of participants on Arm 1c with treatment related adverse events as assessed by CTCAE v5
时间窗: Safety run in of 6 weeks
To determine the safety of NC318 when administered in combination with pembrolizumab in arm 1b
Objective response rate (ORR) in Arm 1a
时间窗: Tumor response will be based on tumor assessments at screening, every 8 weeks from the first dose (for the first 24 weeks) and thereafter every 12 weeks until investigator-assessed initial disease progression, up to 4 years
To determine the objective response rate (ORR) using RECIST v1.1 to NC318 in arm 1a
Objective response rate (ORR) in Arm 1b
时间窗: Tumor response will be based on tumor assessments at screening, every 8 weeks from the first dose (for the first 24 weeks) and thereafter every 12 weeks until investigator-assessed initial disease progression, up to 4 years
To determine the objective response rate (ORR) using RECIST v1.1 to NC318 combined with pembrolizumab in arm 1b
Number of participants in arm 2 with treatment related adverse events as assessed by CTCAE v5
时间窗: Safety run in of 6 weeks
To determine the safety of NC318 when administered in combination with pembrolizumab in arm 2
Number of participants in arm 2a with treatment related adverse events as assessed by CTCAE v5
时间窗: Safety run in of 6 weeks
To determine the safety of NC318 when administered in combination with pembrolizumab in arm 2
Objective response rate (ORR) in Arm 1c
时间窗: Tumor response will be based on tumor assessments at screening, every 8 weeks from the first dose (for the first 24 weeks) and thereafter every 12 weeks until investigator-assessed initial disease progression, up to 4 years
To determine the objective response rate (ORR) using RECIST v1.1 to NC318 combined with pembrolizumab in arm 1b
Objective response rate (ORR) in Arm 2
时间窗: Tumor response will be based on tumor assessments at screening, every 8 weeks from the first dose (for the first 24 weeks) and thereafter every 12 weeks until investigator-assessed initial disease progression, up to 4 years
To determine the objective response rate (ORR) using RECIST v1.1 to NC318 combined with pembrolizumab in arm 2
Objective response rate (ORR) in Arm 2a
时间窗: Tumor response will be based on tumor assessments at screening, every 8 weeks from the first dose (for the first 24 weeks) and thereafter every 12 weeks until investigator-assessed initial disease progression, up to 4 years
To determine the objective response rate (ORR) using RECIST v1.1 to NC318 combined with pembrolizumab in arm 2
次要结局
- Progression-free survival (RECIST v1.1) Arm 1a(Until disease progression or death, up to 4 years)
- Overall Survival (RECIST v1.1) Arm 1a(Until death, up to 5 years)
- Progression-free survival (RECIST v1.1) Arm 1B(Until disease progression or death, up to 4 years)
- Progression-free survival (RECIST v1.1) Arm 2(Until disease progression or death, up to 4 years)
- Overall survival (RECIST v1.1) Arm 2(Until death, up to 5 years)
- Overall survival (RECIST v1.1) Arm 1B(Until death, up to 5 years)
研究者
Scott Gettinger, MD
Professor of Internal Medicine (Medical Oncology)
Yale University