A PHASE 1 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF ESCALATING DOSES OF PF-06940434 IN PATIENTS WITH ADVANCED OR METASTATIC SOLID TUMORS
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 85
- 试验地点
- 31
- 主要终点
- Duration of Response (DR) for Dose Expansion
研究概览
简要总结
Open-label, multi-center, non-randomized, multiple dose, safety, tolerability, pharmacokinetic, and pharmacodynamics and clinical activity study of PF-06940434 (Integrin alpha-V/beta-8 Antagonist) in patients with SCCHN (Squamous Cell Carcinoma of the Head and Neck), renal cell carcinoma (RCC - clear cell and papillary), ovarian, gastric, esophageal, esophageal (adeno and squamous), lung squamous cell, pancreatic and biliary duct, endometrial, melanoma and urothelial tumors. This study contains two parts, single agent dose escalation (Part 1A), dose finding of PF 06940434 in combination with anti-PD-1 (Part 1B) and dose expansion (Part 2). Part 2 Dose Combination Expansion will enroll participants into 3 cohorts at doses determined from Part 1B in order to further evaluate the safety of PF-06940434 in combination with anti-PD-1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Histological or cytological diagnosis of SCCHN, RCC (clear cell and papillary cell), ovarian, gastric, esophageal (adeno and squamous), lung squamous cell, pancreatic and biliary duct, endometrial, melanoma, or urothelial cancer.
- •Arm A SCCHN:
- •Primary tumor location of the oral cavity, oropharynx, hypopharynx or larynx.
- •PDL-1 expression positive and CPS ≥
- •No prior systemic therapy administered in the recurrent or metastatic setting (except for systemic therapy given as part of a multimodal treatment for locally advanced disease).
- •Arm B RCC (clear cell):
- •1 or 2 prior lines of therapy including PD-L1/PD-1 immunotherapy in combination or sequentially with antiangiogenic directed treatment
- •Adequate bone marrow, kidney and liver function.
- •Performance status of 0 or 1.
排除标准
- •Participant disease status is suitable for local therapy administered with curative intent.
- •Hypertension that cannot be controlled by medications.
- •Active or prior autoimmune disease
- •Active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) Hepatitis B, Hepatitis C, and known Human Immunodeficiency Virus infection or Acquired Immunodeficiency Syndrome-related illness
研究组 & 干预措施
Dose Expansion Arm B
PF-06940434 with anti-PD-1 in RCC
干预措施: PF-06801591 (Drug)
Dose Escalation
Single Agent Dose Escalation
干预措施: PF-06940434 (Drug)
Dose Finding Anti-PD-1 Combination 1
Part 1B PF-06940434 plus anti-PD-1
干预措施: PF-06940434 (Drug)
Dose Finding Anti-PD-1 Combination 1
Part 1B PF-06940434 plus anti-PD-1
干预措施: PF-06801591 (Drug)
Dose Expansion Arm A
PF-06940434 with anti-PD-1 in SCCHN
干预措施: PF-06940434 (Drug)
Dose Expansion Arm A
PF-06940434 with anti-PD-1 in SCCHN
干预措施: PF-06801591 (Drug)
Dose Expansion Arm B
PF-06940434 with anti-PD-1 in RCC
干预措施: PF-06940434 (Drug)
Dose Expansion, Arm C
PF-06940434 with anti-PD-1 (both Q3W)
干预措施: PF-06940434 (Drug)
Dose Expansion, Arm C
PF-06940434 with anti-PD-1 (both Q3W)
干预措施: PF-06801591 (Drug)
结局指标
主要结局
Duration of Response (DR) for Dose Expansion
时间窗: Baseline up to 24 Months
Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities
时间窗: Baseline up to approximately 24 months
Number of Participants With Adverse Events (AEs) According to Seriousness
时间窗: Baseline up to up to approximately 24 months
Progression-Free Survival (PFS) for Dose Expansion
时间窗: Baseline up to 24 Months
The period from study entry until disease progression, death or date of last contact.
Objective Response Rate - Percentage of Participants With Objective Response in Dose Expansion
时间窗: Baseline up to 24 months
Number of Participants With Adverse Events (AEs) According to Severity
时间窗: Baseline up to approximately 24 months
Number of Participants With Adverse Events (AEs) by Relationship
时间窗: Baseline up to approximately 24 months
Number of participants with Dose-limiting toxicities (DLT) for Dose Escalation and Dose Finding
时间窗: Baseline up to 28 Days (Cycle 1)
次要结局
- Volume of Distribution (Vd)(Pre-dose on Cycle 1 Day 1 and on days 3, 8, and 15 of Cycle 1; Day 1 and Day 15 of Cycles 2 and 3; Days 1, 3, 8, and 15 of Cycle 4 and Pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days).)
- Incidence and titers of neutralizing antibodies (NAb) against PF-06801591 in Dose Finding and Dose Expansion.(Pre-dose on Days 1 and 15 of Cycle 1, pre-dose on Day 1 of Cycles 2 and 3, pre-dose on Day 1 of Cycle 4, pre-dose on Day 1 of every cycle thereafter and at end of treatment (up to 24 Months) [each cycle is 28 days].)
- Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434.(Cycle 4 Day 1 (each cycle is 28 days))
- Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434 and PF-06801591.(Pre-dose on Cycle 1 Day 1 and on day 15 of Cycle 1; Day 1 of Cycles 2 and 3; Days 1, 3, 8, and 15 of Cycle 4 and Pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days))
- Trough concentrations of PF-06940434 and PF-06801591 in Dose Expansion(Day 1 of Cycle 1 though 4, Day 1 of every 2 Cycles starting from Cycle 5 up to 24 months (each cycle is 28 days). For Part 2 Cohort 3, Day 1 of Every Cycle (each cycle is 21 days))
- PF-06940434 after multiple doses PK parameters (Cmax).(Pre-dose on Cycle 1 Day 1 and on days 3, 8, and 15 of Cycle 1; Day 1 and Day 15 of Cycles 2 and 3; Days 1, 3, 8, and 15 of Cycle 4 and Pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days).)
- Incidence and titers of anti-drug antibodies (ADA) against PF-06940434.(Pre-dose on Days 1 and 15 of Cycle 1, pre-dose on Day 1 of Cycles 2 and 3, pre-dose on Day 1 of Cycle 4, pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days).)
- PK parameters of PF-06940434 and PF-06801591 (Cmax).(Pre-dose on Cycle 1 Day 1 and on day 15 of Cycle 1; Day 1 of Cycles 2 and 3; Days 1, 3, 8, and 15 of Cycle 4 and Pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days))
- Systemic Clearance (CL)(Pre-dose on Cycle 1 Day 1 and on days 3, 8, and 15 of Cycle 1; Day 1 and Day 15 of Cycles 2 and 3; Days 1, 3, 8, and 15 of Cycle 4 and Pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days).)
- Number of participants with increased T-cells after PF-06940434 treatment.(Pre-dose on Day 1 of Cycle 1; pre-dose on Day 1 of Cycles 2 and 3 (each cycle is 28 days))
- Progression-Free Survival (PFS) for Dose Expansion(Baseline to measured progression (up to approximately 24 months))
- Duration of Response (DR)(Baseline up to approximately 24 Months)
- Number of Participants With Objective Response for Dose Expansion portion(Baseline up to 24 months)
- Disease Control Rate (DCR)(Every 8 weeks from the time of enrollment up to 2 years)
- Incidence and titers of neutralizing antibodies (NAb) against PF-06940434.(Pre-dose on Days 1 and 15 of Cycle 1, pre-dose on Day 1 of Cycles 2 and 3, pre-dose on Day 1 of Cycle 4, pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days).)
- Plasma Decay Half-Life (t1/2)(Pre-dose on Cycle 1 Day 1 and on days 3, 8, and 15 of Cycle 1; Day 1 and Day 15 of Cycles 2 and 3; Days 1, 3, 8, and 15 of Cycle 4 and Pre-dose on Day 1 of every cycle thereafter and at end of treatment (up to 24 Months) [each cycle is 28 days])
- Incidence and titers of anti-drug antibodies (ADA) against PF-06801591 in Dose Finding and Dose Expansion(Pre-dose on Days 1 and 15 of Cycle 1, pre-dose on Day 1 of Cycles 2 and 3, pre-dose on Day 1 of Cycle 4, pre-dose on Day 1 of every cycle thereafter and at end of treatment (up to 24 Months) [each cycle is 28 days].)
- Characterize the multiple dose PK of PF-06940434 following intravenous administration in combination with PF-06801591.(Cycle 4 Day 1 (each cycle is 28 days))
- Overall Survival(From baseline to up to 2 years after last dose of study drug)