A Phase II, Open-label, Randomized Controlled Study of PDR001 in Patients With Moderately Differentiated/Undifferentiated Locally Advanced Recurrent or Metastatic Nasopharyngeal Carcinoma Who Progressed on Standard Treatment
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 122
- 试验地点
- 5
- 主要终点
- Progression-free Survival (PFS) as Per RECIST v 1.1 Using Central Assessment - Number of Participants With Progression or Death
研究概览
简要总结
The purpose of this randomized controlled Phase II study is to assess the efficacy of PDR001 versus investigator's choice of chemotherapy in patients with advanced nasopharyngeal carcinoma (NPC).
By blocking the interaction between PD-1 and its ligands PD-L1 and PD-L2, PDR001 leads to the activation of a T-cell mediated antitumor immune response.
详细描述
This was an open-label, multi-center, randomized, and controlled Phase II study to evaluate the efficacy and safety of spartalizumab versus investigator's choice of treatment in subjects with moderately differentiated/undifferentiated locally advanced recurrent or metastatic NPC who progressed on or after first-line treatment.
Participants who met the inclusion/exclusion criteria were randomized in a 2:1 ratio to either investigational arm (spartalizumab) or control arm (commonly used chemotherapy as per investigator's choice). Participants treated with spartalizumab could continue treatment until confirmed progressive disease as per immune-related response criteria (irRC). Participants in the chemotherapy arm were allowed to crossover to spartalizumab if they had radiological progression as per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1) documented by an independent central review and the Investigator believed this was the best treatment option for the patient.
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
- •Histologically documented non-keratinizing locally advanced recurrent or metastatic NPC.
- •Must be resistant to platinum-based chemotherapy (defined as progression on or after platinum-based chemotherapy given in the recurrent/metastatic setting).
- •May have received at least 1 prior therapy for recurrent or metastatic disease, up to 2 prior systemic therapies.
- •An archival tumor specimen or newly obtained tumor sample may be submitted at screening/baseline (a fresh tumor sample is preferred), unless agreed differently between Novartis and the Investigator.
- •At least 1 measurable lesion (as per RECIST v1.1) progressing or new since last anti-tumor therapy.
- •Prior treated brain or meningeal metastases must be without MRI evidence of progression for at least 8 weeks and off systemic steroids for at least 2 weeks prior to screening/baseline.
- •Patient must be willing to undergo testing for human immunodeficiency virus (HIV) if not tested within the past 6 months. If HIV+ positive, patient will be eligible if: his/ her CD4+ count ≥ 300/μL; his/her viral load is undetectable; he/she is currently receiving highly active antiretroviral therapy (HAART).
排除标准
- •History of severe hypersensitivity reactions to other mAbs
- •Active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved asthma/atopy that is treated with broncho-dilators.
- •Active HBV or HCV infections requiring therapy.
- •Prior PD-1- or PD-L1-directed therapy or any therapeutic cancer vaccine.
- •Patients receiving systemic treatment with any immunosuppressive medication.
- •Use of any vaccines against infectious diseases (e.g. varicella, pneumococcus) within 4 weeks of initiation of study treatment.
研究组 & 干预措施
Spartalizumab 400 mg Q4W
anti-PD1 humanized monoclonal antibody. Participants treated with spartalizumab who remained on spartalizumab
干预措施: Spartalizumab (Drug)
Chemotherapy
commonly used chemotherapy as per investigator's choice
干预措施: Investigator choice of chemotherapy (Drug)
结局指标
主要结局
Progression-free Survival (PFS) as Per RECIST v 1.1 Using Central Assessment - Number of Participants With Progression or Death
时间窗: From randomization up to maximum 3.3 years
PFS is the time from the date of randomization to the date of event defined as the first documented confirmed progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Tumor response was based on central review of tumor scan and the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Progressive disease is at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. Number of participants in each category (progression, death, censored) is reported in this record.
Progression-free Survival (PFS) as Per RECIST v 1.1 Using Central Assessment - Median PFS
时间窗: From randomization up to maximum 3.3 years
PFS is the time from the date of randomization to the date of event defined as the first documented confirmed progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Tumor response was based on central review of tumor scan and the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Progressive disease is at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline.
次要结局
- Time to Progression (TTP) as Per RECIST v 1.1(From randomization up to maximum 3.3 years)
- Overall Survival (OS)(From randomization up to maximum 4.8 years.)
- Overall Response Rate (ORR) as Per RECIST v 1.1(From randomization up to maximum 3.3 years)
- Maximum Observed Serum Concentration (Cmax) of Spartalizumab(pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.)
- Number of Participants With Anti-spartalizumab Antibodies(Baseline (pre-dose on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 655 days).)
- Percent Marker Area for CD8 Expression in Tumor Samples(Baseline (screening), Cycle 3 Day 1. The duration of one cycle was 28 days.)
- Duration of Response (DOR) as Per RECIST v 1.1(From randomization up to maximum 3.3 years)
- Time to Reach Maximum Serum Concentration (Tmax) of Spartalizumab(pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.)
- Area Under the Serum Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) of Spartalizumab(pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.)
- Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUCinf) of Spartalizumab(pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.)
- Immune-related Progression-free Survival (irPFS) as Per irRC(From randomization up to maximum 3.3 years)
- Accumulation Ratio (Racc) of Spartalizumab(pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.)
- Terminal Elimination Half-life (T1/2) of Spartalizumab(pre-dose, 1, 24, 168, 336 and 672 hours post spartalizumab dose on Cycle 1 and Cycle 3. The duration of one cycle was 28 days.)
- PD-L1 Percent Positive Tumor(Baseline (screening), Cycle 3 Day 1. The duration of one cycle was 28 days.)
- TIL Count in Tumor Samples(Baseline (screening), Cycle 3 Day 1. The duration of one cycle was 28 days.)
- Fold Change From Baseline in IL-6 Levels in Plasma(Baseline (pre-dose on Cycle 1 Day 1), Cycle 1 Day 15, Cycle 2 Day 15 and end of treatment (assessed up to maximum 4 years). The duration of one cycle was 28 days.)
- Fold Change From Baseline in IFN-gamma Levels in Plasma(Baseline (pre-dose on Cycle 1 Day 1), Cycle 1 Day 15, Cycle 2 Day 15 and end of treatment (assessed up to maximum 4 years). The duration of one cycle was 28 days.)
- Fold Change From Baseline in TNF-alfa Levels in Plasma(Baseline (pre-dose on Cycle 1 Day 1), Cycle 1 Day 15, Cycle 2 Day 15 and end of treatment (assessed up to maximum 4 years). The duration of one cycle was 28 days.)