A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND ANTI-TUMOR ACTIVITY OF PF-07921585 AS A SINGLE AGENT AND IN COMBINATION THERAPY IN PARTICIPANTS 18 YEARS OF AGE AND OLDER WITH ADVANCED SOLID TUMORS
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 4
- 试验地点
- 9
- 主要终点
- Number of Participants With Dose-Limiting Toxicity (DLT) (Parts 1 and 2)
研究概览
简要总结
The purpose of this study is to learn about the safety and effects of the study medicine (called PF-07921585) in people with cancer that has advanced or spread to other parts of the body.
This study is seeking participants who have any of the following cancer types:
- non-small cell lung cancer
- colorectal cancer
- bladder cancer
- melanoma (a type of skin cancer)
- kidney cancer
- head and neck cancer Participants will receive the study medicine PF-07921585 alone or in combination with another study medicine called sasanlimab at the study clinic.
PF-07921585 will be given as an infusion into a vein or as shots under the skin, once every 3 weeks. Sasanlimab will be given as shots under the skin, also once every 3 weeks.
The experiences of participants receiving the study medicine will be studied to help see if the study medicine is safe and effective. Participants may receive study medicine for up to 2 years, depending on how the cancer responds to the study treatment. Participants may continue receiving study medicine after 2 years if there are any benefits from the study treatment. Participants will attend visits once every 3 weeks with the first 9 weeks having more frequent visits, to check the safety of the study treatment.
详细描述
The study contains 3 parts:
Part 1: dose escalation of PF-07921585 as single agent to determine the monotherapy recommended dose for further study.
Part 2: dose escalation of PF-07921585 in combination with the anti-PD 1 inhibitor sasanlimab and potentially other anti-cancer agents, in order to determine the recommended dose for expansion of the combination.
Part 3: dose optimization/ expansion will evaluate PF-07921585 in combination with sasanlimab, and potentially other anti-cancer agents. After identification of the recommended dose for expansion in Part 2, participants with select solid tumors will be enrolled into 3-4 cohorts as follows:
- Cohort 1: Melanoma
- Cohort 2: Microsatellite stable (MSS) metastatic colorectal cancer
- Cohort 3: Non-small cell lung cancer (NSCLC)
- Cohort 4: Solid tumor, tumor types and clinical setting to be determined based on emerging data.
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
- •Participants aged ≥18 years or older at the time of informed consent.
- •Tumor types and prior treatment requirements: Participants entering Parts 2 and 3 must have at least 1 measurable lesion.
- •Part 1 and Part 2:
- •Eligible advanced/metastatic tumor types include NSCLC, urothelial carcinoma (UC), renal cell carcinoma (RCC), melanoma, head and neck squamous cell carcinoma (HNSCC), and microsatellite stable colorectal cancer (MSS-CRC). Participants must have demonstrated radiographic progression on standard treatment(s) for their cancer
- •Cohort 1: Participants with metastatic melanoma with resistance to checkpoint inhibitor therapy and BRAF/MEKi.
- •Cohort 2: Participants with metastatic MSS-CRC.
- •Cohort 3: Participants with previously untreated metastatic NSCLC.
- •ECOG PS 0 or
排除标准
- •Participants with any other active malignancy within 3 years prior to enrollment.
- •Known or suspected hypersensitivity to, or severe allergic history of, human albumin or anti-PD-(L)1 therapy.
- •History of Grade ≥3 immune-related AE (irAE) or unresolved irAEs prior to first dose of study intervention. Exception: vitiligo and endocrinopathy that is controlled with hormonal therapy.
- •History of venous thromboembolic event <12 weeks prior to starting study treatment.
- •Active or history of clinically significant gastrointestinal (GI) disease.
- •Active or history of interstitial lung disease or Grade ≥2 pneumonitis.
- •Active or history of clinically significant autoimmune disease.
- •Active bleeding disorder.
- •Participants who have undergone treatment with any investigational IL-12 agent.
- •Active, uncontrolled infections
研究组 & 干预措施
Part 2
Dose escalation (combination therapy)
干预措施: Sasanlimab (Biological)
Part 1
Dose escalation monotherapy
干预措施: PF-07921585 (Biological)
Part 2
Dose escalation (combination therapy)
干预措施: PF-07921585 (Biological)
Part 3
Dose optimization/ expansion (combination therapy)
干预措施: PF-07921585 (Biological)
Part 3
Dose optimization/ expansion (combination therapy)
干预措施: Sasanlimab (Biological)
结局指标
主要结局
Number of Participants With Dose-Limiting Toxicity (DLT) (Parts 1 and 2)
时间窗: Baseline up to Cycle 2 (each cycle is 21 days)
Specific adverse events occurring during the first 21 days of study medication and considered at least possibly-related to study medication
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs (Parts 1 and 2)
时间窗: Baseline up to 28 days after the last dose of PF-07921585 or after 90 days after the last dose of sasanlimab
AEs are any untoward medical occurrence in a participant who received study drug. Serious adverse event (SAE) are AEs resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 or 90 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities (Parts 1 and 2)
时间窗: Baseline up to 28 days after the last dose of PF-07921585 or after 90 days after the last dose of sasanlimab
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
Objective Response Rate - Percentage of Participants With Objective Response (Part 3)
时间窗: Date of first dose up to 2 years
Percentage of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors 1. 1 (RECIST 1.1). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short aixs was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
次要结局
- Number of Participants with Treatment emergent Adverse Events (AEs) and Serious AEs (Part 3)(Baseline up to 28 days after the last dose of PF-07921585 and 90 days after the last dose of sasanlimab)
- Objective Response Rate-Percentage of Participants with objective response (Parts 1 and 2)(Date of first dose up to 2 years)
- Duration of response (DOR)-Parts 1-3(Date of first dose up to 2 years)
- Disease control rate (DCR)-Parts 1-3(Date of first dose up to 2 years)
- Progression Free survival (PFS)-Parts 1-3(Date of first dose until disease progression or death, up to a maximum of 4 years)
- Overall Survival (OS)-Part 3(Date of first dose until death, up to a maximum of 4 years)
- Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax)-PF-07921585(At specific timepoints from Cycle 1 day 1 up to 2 years)
- Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax ss)-PF-07921585(At specific timepoints from Cycle 1 day 1 up to 2 years)
- Pharmacokinetic Parameters: Area under the curve (AUCt)-PF-07921585(At specific timepoints from Cycle 1 day 1 up to 2 years)
- Pharmacokinetic Parameters: Area under the curve (AUCt ss)-PF-07921585(At specific timepoints from Cycle 1 day 1 up to 2 years)
- Pharmacokinetic Parameters: Cmax (maximum drug concentration in the body)-PF-07921585(At specific timepoints from Cycle 1 day 1 up to 2 years)
- Pharmacokinetic Parameters: Cmax ss (maximum drug concentration in the body)-PF-07921585(At specific timepoints from Cycle 1 day 1 up to 2 years)
- Percentage of Participants With Positive PF-07921585 Anti-Drug Antibody (ADA)(At specific timepoints from Cycle 1 day 1 up to 2 years)
- Percentage of Participants With Positive PF-07921585 neutralizing antibodies (Nab)(At specific timepoints from Cycle 1 Day 1 up to 2 years)
- Incidence and titer of PF-07921585 ADA and Nab(At specific timepoints from Cycle 1 Day 1 up to 2 years)
- Pharmacokinetic Parameters: C through-Sasanlimab(At specific timepoints, predose, from Cycle 1 day 1 up to 2 years)
- Percentage of Participants With Positive sasanlimab Anti-Drug Antibody (ADA)(At specific timepoints from Cycle 1 day 1 up to 2 years)
- Percentage of Participants With Positive sasanlimab neutralizing antibodies (Nab)(At specific timepoints from Cycle 1 Day 1 up to 2 years)
- Incidence and titer of sasanlimab ADA and Nab(At specific timepoints from Cycle 1 Day 1 up to 2 years)