A PHASE 1 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF ESCALATING DOSES OF A VACCINE-BASED IMMUNOTHERAPY REGIMEN (VBIR) FOR PROSTATE CANCER (PF-06753512)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 91
- 试验地点
- 36
- 主要终点
- Number of Participants With AEs Leading to Discontinuation or Dose Reduction
研究概览
简要总结
The study will evaluate the safety, pharmacokinetics and pharmacodynamics of increasing doses of a vaccine-based immunotherapy regimen for patients with prostate cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- Male
- 接受健康志愿者
- 否
入选标准
- •Histological or cytological diagnosis of prostate cancer
- •Adequate bone marrow, kidney and liver function
- •Hormone sensitive relapsing prostate cancer after definitive local therapy (biochemical relapse) OR
- •Failed prior therapy with a novel hormone (e.g. enzalutamide, abiraterone) with documented progressive disease (post-novel hormone therapy CRPC)
排除标准
- •ECOG performance status greater than or equal to 2
- •Concurrent immunotherapy for prostate cancer
- •History of or active autoimmune disorders (including but not limited to: myasthenia gravis, thyroiditis, pneumonitis, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, scleroderma) and other conditions that disorganize or alter the immune system.
- •History of inflammatory bowel disease.
- •Current use of any implanted electronic stimulation device
- •For biochemically relapsed patients, no concurrent use of ADT or orchiectomy and no known prior or current evidence of any metastatic involvement of distant organs
- •For post-novel hormone patients, no concurrent treatment with a secondary hormone (e.g. enzalutamide, abiraterone), no metastasis to the liver or brain
结局指标
主要结局
Number of Participants With AEs Leading to Discontinuation or Dose Reduction
时间窗: Baseline up to 6 months after EOT (52 months in maximum)
An AE was any untoward medical occurrence in a clinical investigation where participant administered a product; the event did not need to have a causal relationship with the treatment.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Baseline up to 6 months after End of Treatment (EOT; 52 months in maximum)
An AE was any untoward medical occurrence in a clinical investigation where participant administered a product; the event did not need to have a causal relationship with the treatment. A SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and non-serious AEs.
Number of Participants With AEs as Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) (Grade >= 3)
时间窗: Baseline up to 6 months after EOT (52 months in maximum)
An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. Grades of AEs were defined by NCI CTCAE v 4.03. Grade 1=asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL); Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5= death related to AE. Treatment-emergent adverse events occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Number of Participants With Dose-Limiting Toxicities (DLTs)
时间窗: The first 28 days following the first AdC68 vaccination (on Cycle 1 Day 1)
The following AEs occurring in the first 28 days following the first AdC68 vaccination and not related to disease/progression were DLTs: (a) hematologic (Cohorts 1A to 3A and Cohorts 6A to 9A): Grade 3 neutropenia lasting \>7 days, febrile neutropenia, Grade \>=3 neutropenic infection, Grade \>=3 thrombocytopenia, Grade \>=3 anemia lasting \>7 days, Grade \>=3 lymphopenia lasting \>14 days; (b) non-hematologic (all cohorts): Grade \>=3 laboratory abnormalities either associated with symptoms or associated with worsening of an existing condition or that suggested a new disease process or that required additional active management, Grade \>=3 toxicities, Grade 3 flu like symptoms lasting \>3 days, fever of \>40.0 degree Celsius lasting \>3 days. Other clinically important or persistent toxicities at discretion of investigator and Pfizer.
次要结局
- Change From Baseline in T Cell Response to Prostate Stem Cell Antigen (PSCA) in Part A(At screening; Cycle 1: at Day 1, Day 15, Day 29, Day 43, Day 71; Cycle 2: at Day 1, Day 29, and Day 99; at the EOT visit, and 2, 4 and 6 months after EOT.)
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Tremelimumab in Part A(Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT.)
- Number of Participants With Laboratory Abnormalities in Hematology (Grade 3 or 4)(Baseline up to 6 months after EOT (52 months in maximum))
- Baseline for PSA in Part B(At screening and Cycle 1 Day 1.)
- Number of Participants With Laboratory Abnormalities in Urinalysis (Grade 3 or 4)(Baseline up to 6 months after EOT (52 months in maximum))
- Trough Concentrations (Ctrough) After Multiple Dosing of Tremelimumab(Pre-dose on Cycle 2 Day 1)
- Ctrough of PF-06801591(Pre-dose on Cycle 2 Day 1)
- Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Cohort 7A and 3B Combined and All mCRPC Patients(Baseline up to 6 months after EOT (52 months in maximum))
- Number of Participants With Laboratory Abnormalities in Chemistry (Grade 3 or 4)(Baseline up to 6 months after EOT (52 months in maximum))
- Change From Baseline in T Cell Response to Prostate Specific Antigen (PSA) in Part A(At screening; Cycle 1: at Day 1, Day 15, Day 29, Day 43, Day 71; Cycle 2: at Day 1, Day 29, and Day 99; at the EOT visit, and 2, 4 and 6 months after EOT.)
- Change From Baseline in T Cell Response to Prostate Specific Membrane Antigen (PSMA) in Part A(At screening; Cycle 1: at Day 1, Day 15, Day 29, Day 43, Day 71; Cycle 2: at Day 1, Day 29, and Day 99; at the EOT visit, and 2, 4 and 6 months after EOT.)
- Maximum Observed Plasma Concentration (Cmax) of Tremelimumab in Part A(Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT.)
- AUClast of PF-06801591 in Part A(Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT.)
- Titer of Treatment-Induced ADA Against Tremelimumab(Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to tremelimumab dosing.)
- Baseline for PSA Velocity in Part B(At screening and Cycle 1 Day 1.)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tremelimumab in Part A(Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT.)
- Tmax of PF-06801591 in Part A(Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT.)
- Number of Participants With Anti-Drug Antibody (ADA) Against Tremelimumab(Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to tremelimumab dosing.)
- Titer of Treatment-Induced NAb Against Tremelimumab(Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to tremelimumab dosing.)
- Titer of Treatment-Induced ADA Against PF-06801591(Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to PF-06801591 dosing.)
- Number of Participants With NAb Against PF-06801591(Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to PF-06801591 dosing.)
- Radiographic Progression Free Survival (rPFS) Per RECIST v1.1 in Cohort 7A and 3B Combined , All mCRPC Patients, Cohort 1B, and Cohort 5B(Baseline up to 6 months after EOT (52 months in maximum))
- Duration of PSA-50 Response in Part B(Days 1, 29, 57 of Cycle 1 and Cycle 2.)
- Baseline for PSA Slope in Part B(At screening and Cycle 1 Day 1.)
- Cmax of PF-06801591 in Part A(Cycle 1: at Day 1 pre-dose, any time between 48 to 120 hr, approximately 168 hr, 336 hr, and 504 hr, at pre-dose on Day 29, Day 57, and Day 85; Cycle 2: at pre-dose on Day 1 and Day 29; at EOT visit, and 2, 4 and 6 months after EOT.)
- Number of Participants With ADA Against PF-06801591(Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to PF-06801591 dosing.)
- Titer of Treatment-Induced NAb Against PF-06801591(Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to PF-06801591 dosing.)
- Number of Participants With Neutralizing Antibody (NAb) Against Tremelimumab(Cycle 1: at Day 1, Day 29, and Day 85; Cycle 2: at Day 29; at the EOT visit, and 2, 4 and 6 months after EOT. Samples collected on dosing days were obtained within 6 hours prior to tremelimumab dosing.)
- Duration of Response (DOR) by RECIST v1.1 in Cohort 7A and 3B Combined and All mCRPC Patients(Baseline up to 6 months after EOT (52 months in maximum))
- Number of Participants Achieving Central PSA Response >= 50% Decline From Baseline (PSA-50) in Part B(At screening; Cycle 1 and 2: at Day 1, Day 29, Day 57, and Day 85; at the EOT visit, and 1, 2, 4 and 6 months after EOT.)
- Baseline for PSA Doubling Time (PSADT) in Part B(At screening and Cycle 1 Day 1.)
- Immune-Related Confirmed ORR by Immune Related Response Evaluation Criteria in Solid Tumors Version 1.1 (irRECIST v1.1) in Cohort 7A and 3B Combined and All mCRPC Patients(Baseline up to 6 months after EOT (52 months in maximum))
- Immune-Related Confirmed DOR by irRECIST v1.1 in Cohort 7A and 3B Combined and All mCRPC Patients(Baseline up to 6 months after EOT (52 months in maximum))
- Number of Patients With Bone Progression Per Prostrate Cancer Working Group 3 (PCWG3) Criteria in Cohort 7A and 3B Combined(Baseline up to 6 months after EOT (52 months in maximum))
- Change in PSADT at Post-Treatment Visit From Baseline in Part B(At screening; Cycle 1 and 2: at Day 1, Day 29, Day 57, and Day 85; at the EOT visit, and 1, 2, 4 and 6 months after EOT.)
- Change in PSA Slope at Post-Treatment Visit From Baseline in Part B(At screening; Cycle 1 and 2: at Day 1, Day 29, Day 57, and Day 85; at the EOT visit, and 1, 2, 4 and 6 months after EOT.)
- Change in PSA Velocity at Post-Treatment Visit From Baseline in Part B(At screening; Cycle 1 and 2: at Day 1, Day 29, Day 57, and Day 85; at the EOT visit, and 1, 2, 4 and 6 months after EOT.)