A Phase 1b/2 Open-Label Study to Evaluate Pharmacokinetics, Safety, Efficacy, and Pharmacodynamics of PF-06801591 (PD-1 Inhibitor) in Participants With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Pfizer
- 入组人数
- 155
- 试验地点
- 48
- 主要终点
- Phase 2: AUCτ of PF-06801591 at Steady State
研究概览
简要总结
This is a Phase 1b/2 protocol to evaluate pharmacokinetics, safety, efficacy, and pharmacodynamics of PF-06801591, a programmed death-1(PD-1) antagonist monoclonal antibody (mAb) in participants with advanced malignancies.
This study consists of 2 parts:
Phase 1b part (dose escalation and dose expansion) in patients with advanced malignancies in Asia and a global Phase 2 part in non small cell lung cancer (NSCLC) patients.
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
- •Age ≥18 years (≥ 20 years in Japan; ≥ 19 years in South Korea)
- •Easter Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Adequate bone marrow function, renal and liver functions Phase 1b
- •Histological or Cytological diagnosis of advanced solid tumor with clinical evidence of response to anti-PD-1 or PD-L1 agent
- •Participant must have received at least 1 prior line of therapy for recurrent or metastatic disease, and must have progressed/relapsed, be refractory, or intolerant to standard therapy approved for the specific tumor type Phase 2
- •Participants must have a documented diagnosis of stage III where participants are not candidates for surgical resection or definitive chemoradiation, or stage IV NSCLC
- •EGFR mutation, BRAF mutation, and ALK or ROS1 translocation/rearrangement are not permitted
- •Participants whose tumor is known to be PD-L1 positive (Tumor Proportion Score [TPS] ≥1%) or unknown are eligible
- •Up to 1 line of prior therapy in advanced or metastatic disease settings allowed
- •Participant should not have received prior treatment with anti PD-1/PD-L1 drugs
- •At least one measurable lesion as defined by RECIST version 1.1
排除标准
- •Participants with known symptomatic brain metastases requiring steroids
- •Participants with Interstitial Lung Disease history or complication
- •Q-T interval corrected for heart rate QTc > 450 msec for male participants or QTc > 470 msec for female participants or QTc > 480 msec in participants with right bundle branch block.
- •Hypertension that cannot be controlled by medications (eg, systolic > 150 mmHg and diastolic > 90 mmHg) despite optimal medical therapy.
- •Known or suspected hypersensitivity to active ingredient or excipients of the study drug.
- •History of Grade ≥3 immune mediated AE (including AST/ ALT elevations that where considered drug related and cytokine release syndrome [CRS]) that was considered related to prior immune modulatory therapy (eg, immune checkpoint inhibitors, co-stimulatory agents, etc.) and required immunosuppressive therapy (For Phase 1b only).
- •Vaccination with live attenuated vaccines within 4 weeks prior to randomization is prohibited; however inactivated vaccines are permitted.
研究组 & 干预措施
Arm B2 (Phase 2)
干预措施: PF-06801591 (Drug)
Arm A1 (Phase 1b)
干预措施: PF-06801591 (Drug)
Arm A2 (Phase 2)
干预措施: PF-06801591 (Drug)
Arm B1 (Phase 1b)
干预措施: PF-06801591 (Drug)
结局指标
主要结局
Phase 2: AUCτ of PF-06801591 at Steady State
时间窗: Phase 2: Cycle 4 Day 1, 8, 15, 22 and Cycle 5 Day 1 for the PF-06801591 300 mg SC Q4W arm, and Cycle 3 Day 1, 8, 15, 29 and Cycle 4 Day 1 for the PF-06801591 600 mg SC Q6W arm
This study included Asian participants with advanced solid tumors (Phase 1b) and global participants with 1L and 2L NSCLC (Phase 2). AUCτ is area under the plasma concentration-time profile from time zero to the next dose (at steady state, starting at Week 12). (τ = X days, where X = 28 days for Q4W regimen and 42 days for Q6W regimen)
Phase 2: Ctrough of PF-06801591 at Steady State, at Week 12
时间窗: Phase 2: Cycle 4 Day 1 for the PF-06801591 300 mg SC Q4W arm, and Cycle 3 Day 1 for the PF-06801591 600 mg SC Q6W arm
This study included Asian participants with advanced solid tumors (Phase 1b) and global participants with 1L and 2L NSCLC (Phase 2). Steady state Ctrough is pre-dose concentration following multiple dosing at steady state (Week 12)
Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLT)
时间窗: Phase 1b: at the end of cycle 1 (28 days) for the PF-06801591 300 mg SC Q4W arms, and (42 days) for the PF-06801591 600 mg SC Q6W arms
This study included Asian participants with advanced solid tumors (Phase 1b) and global participants with first line (1L) and second line (2L) non-small cell lung cancer (NSCLC) (Phase 2). For the Phase 1b, any of the following AEs occurring during the DLT observation period (the first cycle of treatment) which were attributable to the investigational product were classified as DLTs: Grade 5 AE not clearly due to the underlying disease or extraneous causes; Hematologic toxicity; Non-Hematologic Toxicity; Delay of ≥ 3 weeks in receiving the next scheduled administration due to persisting treatment-related toxicities.
次要结局
- Number of Participants With Treatment-Emergent Adverse Events(Phase 1b/2: On-treatment period is defined as the time from the first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer drug therapy - 1 day).)
- Number of Participants With Laboratory Abnormalities(Phase 1b/2: On-treatment period is defined as the time from the first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer drug therapy - 1 day).)
- Pharmacokinetic Parameters: AUCτ After First Dose(Phase 1b/2: For the PF-06801591 300 mg SC Q4W arms, Cycle 1 Day 1, 8, 15, 22, Cycle 2 Day 1; for the PF-06801591 600 mg SC Q6W arms, Cycle 1 Day 1, 8, 15, 29, Cycle 2 Day 1)
- Number of Participants With Objective Response (Complete Response + Partial Response) Reported by Baseline Programmed Death-Ligand 1 (PD-L1) Status (High, Low, and Unknown)(Phase 1b/2: Baseline up to 30 months)
- Number of Participants With Treatment-Induced Anti-Drug Antibody (ADA) /Neutralizing Antibodies (NAb)(Phase 1b/2: Day 1 of Cycle 1, 2, 3, 4, 6, 8, 10 and end of treatment (EOT) for the PF-06801591 300 mg SC Q4W arms; Day 1 of Cycle 1, 2, 3, 4, 5, 7 and EOT for the PF-06801591 600 mg SC Q6W arms)
- Number of Participants With Objective Response (OR)(Phase 1b/2: Up to 30 months)
- Pharmacokinetic Parameters: Ctrough After First Dose(Phase 1b/2: Cycle 2 Day 1 for all Arms)
- Pharmacokinetic Parameters: Ctrough at Steady State(Phase 1b/2: For the PF-06801591 300 mg SC Q4W arms, Day 1 of Cycle 4; for the PF-06801591 600 mg SC Q6W arms, Day 1 of Cycle 3)
- Time to Response (TTR)(Phase 1b/2: Up to 30 months)