A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTITUMOR ACTIVITY OF PF-07257876 IN PATIENTS WITH ADVANCED OR METASTATIC TUMORS
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 29
- 试验地点
- 84
- 主要终点
- Number of participants with adverse events (AEs)
研究概览
简要总结
This is a first-in-human, Phase 1, open label, multicenter, multiple dose, dose escalation and dose expansion study intended to evaluate the safety, pharmacokinetic, pharmacodynamic and potential clinical benefit of PF-07257876, a CD47-PD-L1 bispecific antibody, in participants with selected advanced or metastatic tumors for whom no standard therapy is available. The study contains 2 parts, single agent Dose Escalation (Part 1) to determine the recommended dose of PF-07257876, 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological/cytological diagnosis of selected advanced or metastatic tumor
- •Prior treatment with PD-1 (Programmed cell death 1) or PD-L1 (programmed death-ligand 1) in NSCLC and SCCHN or platinum-based therapy in Ovarian cancer
- •Confirmed radiographic progression of disease
- •PD-L1 IHC positivity ≥1%
- •Have ≥1 measurable lesion as defined by RECIST 1.1 that has not been previously irradiated
- •Eastern Cooperative Oncology Group performance status 0-1
- •Adequate hematologic, renal and liver functions
- •Resolved acute effects of any prior therapy
- •Participants in Part 1 must be able to provide archival tumor tissue collected within the prior 6 months or consent to undergo a fresh biopsy during screening. Participants enrolled to the MTD (Maximum Tolerated Dose) cohort in Part 1 must consent to mandatory paired pre-treatment and on-treatment biopsies. Participants in Part 2 must consent to a pre-treatment biopsy and a subset of patients must consent to a paired on-study biopsy as well until the Sponsor deems an adequate number have been received.
排除标准
- •Participants with known brain metastasis larger than 4 cm or that is symptomatic. New brain metastases detected at screening. Participants with previously diagnosed brain metastases are eligible if they have completed treatment and recovered from acute effects prior to study entry.
- •Abnormal neurological assessment by investigator
- •Other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ
- •Major surgery or radiation therapy within 4 weeks prior to planned first dose
- •Last systemic anti-cancer therapy within 28 days or 5 half-lives (whichever is shorter) prior to planned first dose (6 weeks for mitomycin C or nitrosoureas)
- •Active bleeding disorder in the past 6 months prior to first dose
- •History of clinically significant severe immune mediated adverse event that was considered related to prior immune modulatory therapy and required immunosuppressive therapy (other than hormone replacement therapy)
- •History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (ie, bronchiolitis obliterans, cryptogenic organizing pneumonia), evidence of active pneumonitis on screening chest CT(computer tomography) scan
- •Anticoagulation with vitamin K antagonists or factor Xa inhibitors is not allowed
- •Treatment with chronic systemic corticosteroids or other immunosuppressive medications
- •Participation in other studies involving investigational drug(s) within 4 weeks prior to planned first dose
- •Active, uncontrolled bacterial, fungal, or viral infection, Hepatitis B, Hepatitis C, or Human immunodeficiency virus (HIV) infection
- •Active COVID-19/SARS-CoV2
- •Pregnant or breastfeeding female participant
- •Organ transplant requiring immunosuppressive treatment or prior allogeneic bone marrow or hematopoietic stem cell transplant
- •Significant cardiac or pulmonary conditions or events within previous 6 months
研究组 & 干预措施
Dose Expansion (Part 2) - Cohort 2 (SCCHN)
Participants with squamous cell carcinoma of the head and neck (SCCHN) will receive PF-07257876 at the recommended dose from Part 1.
干预措施: PF-07257876 (Biological)
Dose Escalation (Part 1)
Participants will receive PF-07257876 at escalating dose levels.
干预措施: PF-07257876 (Biological)
Dose Expansion (Part 2) - Cohort 1 (NSCLC)
Participants with non-small cell lung cancer (NSCLC) will receive PF-07257876 at the recommended dose from Part 1.
干预措施: PF-07257876 (Biological)
结局指标
主要结局
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 the Expansion cohorts (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
Number of participants with dose limiting toxicities (DLTs) in Dose Escalation (Part 1)
时间窗: Baseline through end of Cycle 1 (each cycle is 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
次要结局
- Single dose PK parameter: Area under the Curve (AUClast) in Part 1(Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years)
- Multiple dose PK parameter: Maximal concentration (Cmax, ss) in Part 1(Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years)
- Multiple dose PK parameter: Time to maximal plasma concentration (Tmax, ss) in Part 1(Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years)
- Duration of response (DOR)(Baseline through up to 2 years or until disease progression)
- Progression free survival (PFS)(Baseline through up to 2 years or until disease progression)
- Time to progression (TTP)(Baseline through up to 2 years or until disease progression)
- Single dose PK parameter: Time to maximal plasma concentration (Tmax) in Part 1(Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years)
- Intratumor PD-L1 expression(Baseline through Cycle 2 Day 15 (each cycle is 28 days))
- ORR in Dose Escalation (Part 1)(Baseline through up to 2 years or until disease progression)
- Immunogenicity of PF-07257876(Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years)
- Intratumor T cell levels(Baseline through Cycle 2 Day 15 (each cycle is 28 days))
- Single dose Pharmacokinetics (PK) parameter: Maximal concentration (Cmax) in Part 1(Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years)
- Multiple dose PK parameter: Area under the Curve (AUCtau, ss) in Part 1(Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years)
- Lowest concentration (Ctrough) reached before the next dose is administered in Part 2(Pre-dose on Day 1 at Cycles 1, 2, 3, 4, 5 and every third cycle thereafter (each cycle is 28 days) and End of Treatment visit, up to 2 years)
- Overall Survival (OS) in the Expansion Cohorts (Part 2)(Baseline through up to 2 years or until disease progression)