A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND EXPANSION STUDY OF PF-07265028 AS A SINGLE AGENT AND IN COMBINATION WITH SASANLIMAB EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTI-TUMOR ACTIVITY OF PF-07265028 IN PARTICIPANTS 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
- 21
- 试验地点
- 8
- 主要终点
- Number of participants with Dose-limiting toxicities (DLTs) in Dose Escalation (Part 1)
研究概览
简要总结
The purpose of this study is to assess the safety and effects of PF-07265028 as monotherapy and in combination with sasanlimab.
The study aims to identify the maximum tolerated dose (MTD) of PF-07265028 as monotherapy; evaluate the clinical activity of monotherapy and combination; and select the recommended dose of PF-07265028 monotherapy and in combination for potential further studies and development.
The study contains 2 parts, Dose Escalation (Part 1) to determine the recommended dose of PF-07265028 as single agent and in combination, followed by Dose Expansion (Part 2) in selected tumor types at the recommended dose.
It is expected that most participants will take part in this study for up to 1 year with six on-site visits in the first month and then at least twice every subsequent month while they are on treatment.
详细描述
The purpose of this first-in-human study is to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of increasing doses of PF-07265028 as monotherapy and in combination with sasanlimab; identify the maximum tolerated dose (MTD) of PF-07265028 monotherapy; evaluate the clinical activity of monotherapy and combination; and select the recommended dose of PF-07265028 monotherapy and in combination for potential further studies and development. The study contains 2 parts, Dose Escalation (Part 1) to determine the recommended dose of PF-07265028 as single agent and in combination, followed by Dose Expansion (Part 2) in selected tumor types at the recommended dose.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Across all cohorts:
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- •Adequate hematological, kidney and liver function
- •Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.
- •Resolved acute effects of any prior therapy
- •All participants must provide archival formalin-fixed paraffin-embedded (FFPE) tumor tissue:
- •Part 1: If archival sample is older than 6 months, the participant must consent to undergo a fresh biopsy during the screening.
- •Part 2 Fresh tumor biopsy during screening is required unless there is archival tissues less than 3 months old and subsequent to the last systemic anti-cancer therapy.
- •Part 1A Monotherapy:
- •Histologically or cytologically confirmed advanced or metastatic solid tumors which have progressed following systemic anticancer therapies, or are resistant to standard therapy or for which no standard therapy is available, or for whom standard therapy is not tolerated.
- •Part 1B Combination Therapy:
- •Histologically or cytologically confirmed advanced or metastatic solid tumor which have progressed following systemic anticancer therapies, including at least 1 checkpoint inhibitor.
- •Part 2 Dose Expansion:
- •Histologically or cytologically confirmed advanced or metastatic malignancies, including gastric/Gastroesophageal junction cancer, Head and neck squamous cell carcinoma, or urothelial cancer (non-small cell lung cancer and other solid tumors may be included) who have progressed following systemic anticancer therapies, including at least 1 checkpoint inhibitor
排除标准
- •Participants with any other active malignancy within 3 years prior to enrollment
- •Participants with active autoimmune conditions or history of autoimmune diseases that may relapse
- •History of interstitial lung disease, pneumonitis (non-infectious) or uncontrolled lung diseases
- •History of prior immune-related adverse events (irAEs) Grade ≥3
- •Central nervous system metastases
- •Significant cardiac or pulmonary conditions or events within previous 6 months
- •Active, uncontrolled bacterial, fungal, or viral infection
- •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PF-07265028
- •Prior administration of HPK1 inhibitor
研究组 & 干预措施
Part 1A Dose Escalation Monotherapy
Participants will receive PF-07265028 at escalating dose levels.
干预措施: PF-07265028 (Drug)
Part 1B Dose Escalation Combination
Participants will receive PF-07265028 at escalating dose levels in combination with sasanlimab fixed dose
干预措施: PF-07265028 (Drug)
Part 1B Dose Escalation Combination
Participants will receive PF-07265028 at escalating dose levels in combination with sasanlimab fixed dose
干预措施: Sasanlimab (Biological)
Part 2A Dose Expansion Combination (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
干预措施: PF-07265028 (Drug)
Part 2A Dose Expansion Combination (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
干预措施: Sasanlimab (Biological)
Part 2A Dose Expansion Combination (UC)
Participants with urothelial cancer (UC) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
干预措施: PF-07265028 (Drug)
Part 2A Dose Expansion Combination (UC)
Participants with urothelial cancer (UC) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
干预措施: Sasanlimab (Biological)
Part 2A Dose Expansion Combination (Gastric/GEJ)
Participants with gastric/gastroesophageal junction cancer (Gastric/GEJ) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
干预措施: PF-07265028 (Drug)
Part 2A Dose Expansion Combination (Gastric/GEJ)
Participants with gastric/gastroesophageal junction cancer (Gastric/GEJ) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
干预措施: Sasanlimab (Biological)
Part 2A Dose Expansion Combination (NSCLC)
Participants with non small cell lung cancer (NSCLC) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
干预措施: PF-07265028 (Drug)
Part 2A Dose Expansion Combination (NSCLC)
Participants with non small cell lung cancer (NSCLC) will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
干预措施: Sasanlimab (Biological)
Part 2A Dose Expansion Combination (selected tumor types)
Participants with selected tumor types will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
干预措施: PF-07265028 (Drug)
Part 2A Dose Expansion Combination (selected tumor types)
Participants with selected tumor types will receive PF-07265028 in combination with sasanlimab at the recommended dose from Part 1B
干预措施: Sasanlimab (Biological)
Part 2B Dose Expansion Monotherapy (selected tumor types)
Participants with selected tumor types will receive PF-07265028 single agent at the recommended dose from Part 1A.
干预措施: PF-07265028 (Drug)
结局指标
主要结局
Number of participants with Dose-limiting toxicities (DLTs) in Dose Escalation (Part 1)
时间窗: Cycle 1 (28 days)
DLTs will be evaluated during Cycle 1 (a cycle is 28 days) in Part 1. The number of DLTs will be used to determine the optimal dose
Number of participants with adverse events (AEs)
时间窗: Baseline through up to 2 years
AEs characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] version 5.0), timing, seriousness, and relationship to study therapy.
Number of participants with clinically significant laboratory abnormalities
时间窗: Baseline through up to 2 years
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
Objective response rate (ORR) in Dose Expansion (Part 2)
时间窗: Baseline through up to 2 years or until disease progression
Tumor response based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
次要结局
- The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through Cmax.(Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days))
- The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through Tmax.(Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days))
- The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through AUC(Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days))
- The effect of food on the pharmacokinetic profile of PF-07265028 through Cmax.(Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days))
- The effect of food on the pharmacokinetic profile of PF-07265028 through Tmax(Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days))
- The effect of food on the pharmacokinetic profile of PF-07265028 through AUC(Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days))
- ORR in Dose Escalation (Part 1)(From baseline through disease progression or study completion (approximately 2 years))
- The pharmacokinetic profile of sasanlimab when given in combination with PF-07265028 through Cmin(Day 1 of cycle 1 (each cycle is 28 days), Day 1 of cycle 2, Day 1 of cycle 3, Day 1 of cycle 5 and thereafter every 6 cycles (each cycle is 28 days))
- The immunogenicity of sasanlimab when given in combination with PF-07265028 through ADA and NAb(Day 1 of cycle 1 (each cycle is 28 days), Day 1 of cycle 2, Day 1 of cycle 3, Day 1 of cycle 5 and thereafter every 6 cycles (each cycle is 28 days))
- Time to event endpoints (OS) in Dose Expansion (Part 2)(From baseline through disease progression or study completion (approximately 2 years))
- The effect of PF-07265028 alone and in combination with sasanlimab on tumor immune biomarkers modulation(Baseline through up to 2 years)
- Time to event endpoints (DOR) in Dose Expansion (Part 2)(From baseline through disease progression or study completion (approximately 2 years))
- Time to event endpoints (PFS) in Dose Expansion (Part 2)(From baseline through disease progression or study completion (approximately 2 years))