A PHASE 1, OPEN-LABEL, MULTI-CENTER, DOSE-FINDING, PHARMACOKINETIC, SAFETY AND TOLERABILITY STUDY OF PF 07265807 IN PARTICIPANTS WITH SELECTED ADVANCED OR METASTATIC SOLID TUMOR MALIGNANCIES
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 88
- 试验地点
- 59
- 主要终点
- Parts 1, 2, and 3: Number of participants with dose limiting toxicities (DLTs)
研究概览
简要总结
A First-in-Human Pharmacokinetic, Safety, and Tolerability Study of PF-07265807 as Monotherapy and in Combination in Participants with Advanced or Metastatic Solid Tumors
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
- •At least one measurable (Parts 1-4) or non-measurable lesion (Parts 1-3), not previously irradiated, as defined by RECIST 1.1
- •ECOG Performance Status 0 or 1, 2 with approval
- •Adequate Bone Marrow Function
- •Adequate Renal Function
- •Adequate Liver Function
- •Resolved acute effects of any prior therapy
- •Able to provide adequate archival tumor tissue or freshly obtained tumor tissue (some participants will require mandatory pre- and on-treatment biopsy is part of the biomarker cohort).
- •Life expectancy of at least 3 months.
- •Part 1 and Part 2: Participants who are intolerant or resistant to standard treatment for selected solid tumors.
- •Part 3: Participants with advanced/metastatic RCC with a clear cell component and progressed with no standard therapy available.
- •Part 4, Cohort 1: Participants with NSCLC with METex14-skipping alteration(s) and progressed on at least 1 prior therapy.
- •Part 4, Cohort 2: Participants with MSS CRC with intermediate TMB and progressed with no satisfactory alternative treatment available, but has not received prior treatment with an anti-PD-(L)1 therapy.
- •Part 4, Cohort 3: Participants with metastatic gastric or GEJ adenocarcinoma that is PD-L1 positive that has progressed on at least 2 but no more than 3 prior chemotherapy regiments, but has not received prior treatment with an anti-PD-(L)1 therapy.
- •Part 4, Cohort 4: Participants with metastatic RCC with a clear cell component with IMDC intermediate or poor risk that have not received any prior systemic therapy for metastatic disease.
排除标准
- •Known active uncontrolled or symptomatic CNS metastases.
- •Any other active malignancy within 2 years prior to enrollment.
- •Major surgery within 6 weeks, radiation therapy within 4 weeks, systemic anti-cancer therapy within 2 week or 5 half-lives (4 weeks or 5 half-lives for antibody therapies or investigational drug(s) taken on another study) prior to study entry.
- •Active or history of autoimmune disease requiring >10mg/day prednisone or other concurrent immunosuppressive therapy.
- •Active, uncontrolled infection (controlled HBV, HCV, HIV/AIDS may be allowed) as defined in protocol.
- •Retinal or other serious ophthalmic disorders as defined in protocol.
- •Clinically significant cardiac disease as defined in protocol.
- •Uncontrolled HTN that cannot be controlled by medications.
- •Inability to consume or absorb study drug.
- •Known or suspected hypersensitivity to PF-
- •Prohibited concomitant medications as defined in protocol.
- •Active inflammatory GI disease, uncontrollable chronic diarrhea, or previous gastric resection or lap band surgery affecting absorption.
- •Active bleeding disorder.
- •Discontinuation of prior checkpoint inhibitor for treatment-related toxicity.
- •Experienced >= G3 treatment-related irAE with prior PD-(L)1 agent.
- •Prior treatment with selective AXL/MERTK inhibitors
- •For participants receiving sasanlimab:
- •- Known history of non-infectious pneumonitis that required steroid treatment or current pneumonitis.
研究组 & 干预措施
Expansion Phase: Part 4, Cohort 3
PF-07265807 with sasanlimab in participants with PD-L1+ gastric cancer/GEJ
干预措施: Sasanlimab (Drug)
Monotherapy Dose Escalation: Part 1
Monotherapy dose escalation of PF-07265807 in participants with select tumor types.
干预措施: PF-07265807 (Drug)
Doublet Dose Escalation: Part 2
Doublet combination dose escalation of PF-07265807 with sasanlimab in participants with select tumor types. PF-07265807 will dose escalate. Sasanlimab dose will stay constant.
干预措施: PF-07265807 (Drug)
Doublet Dose Escalation: Part 2
Doublet combination dose escalation of PF-07265807 with sasanlimab in participants with select tumor types. PF-07265807 will dose escalate. Sasanlimab dose will stay constant.
干预措施: Sasanlimab (Drug)
Triplet Dose Escalation: Part 3
Triplet combination dose escalation of PF-07265807 with sasanlimab plus axitinib in participants with select tumor types. PF-07265807 will dose escalate. Sasanlimab dose will stay constant. Axitinib dose will follow label.
干预措施: PF-07265807 (Drug)
Triplet Dose Escalation: Part 3
Triplet combination dose escalation of PF-07265807 with sasanlimab plus axitinib in participants with select tumor types. PF-07265807 will dose escalate. Sasanlimab dose will stay constant. Axitinib dose will follow label.
干预措施: Sasanlimab (Drug)
Expansion Phase: Part 4, Cohort 2
PF-07265807 with sasanlimab in participants with MSS CRC
干预措施: Sasanlimab (Drug)
Expansion Phase: Part 4, Cohort 1
PF-07265807 monotherapy in participants with METex14 mutant NSCLC.
干预措施: PF-07265807 (Drug)
Expansion Phase: Part 4, Cohort 2
PF-07265807 with sasanlimab in participants with MSS CRC
干预措施: PF-07265807 (Drug)
Expansion Phase: Part 4, Cohort 3
PF-07265807 with sasanlimab in participants with PD-L1+ gastric cancer/GEJ
干预措施: PF-07265807 (Drug)
Triplet Dose Escalation: Part 3
Triplet combination dose escalation of PF-07265807 with sasanlimab plus axitinib in participants with select tumor types. PF-07265807 will dose escalate. Sasanlimab dose will stay constant. Axitinib dose will follow label.
干预措施: Axitinib (Drug)
Expansion Phase: Part 4, Cohort 4
PF-07265807 with sasanlimab plus axitinib in participants with RCC
干预措施: PF-07265807 (Drug)
Expansion Phase: Part 4, Cohort 4
PF-07265807 with sasanlimab plus axitinib in participants with RCC
干预措施: Sasanlimab (Drug)
Expansion Phase: Part 4, Cohort 4
PF-07265807 with sasanlimab plus axitinib in participants with RCC
干预措施: Axitinib (Drug)
结局指标
主要结局
Parts 1, 2, and 3: Number of participants with dose limiting toxicities (DLTs)
时间窗: Baseline through day 21 or 42
DLTs will be evaluated during the first cycle (day 21) or two cycles (day 42). The number of DLTs will be used to determine the maximum tolerated dose (MTD)
Parts 1, 2, and 3: Number of participants with laboratory abnormalities
时间窗: Baseline through approximately 2 years
Laboratory abnormalities as characterized by type, frequency, severity, and timing.
Part 4, Cohort 4: Complete Response (CR)
时间窗: Baseline through approximately 2 years
Response will be evaluated via radiographical tumor assessment by RECIST v1.1
Parts 1, 2 and 3: Number of participants with treatment emergent adverse events (AEs)
时间窗: Baseline through approximately 2 years
AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
Part 4: Overall Response Rate (ORR)
时间窗: Baseline through approximately 2 years
Response will be evaluable via radiographical tumor assessment by RECIST v1.1
次要结局
- Part 3: Maximum plasma concentration at steady state (Cmax,ss) of axitinib(Each cycle is 21 days. Cycle 1 Day 1 predose; Cycle 1 Day 14 predose, 0.5,1,2,4, and 8 hours post dose)
- Parts 1, 2, and 3: Time to reach maximum plasma concentration (Tmax) of PF-07265807 and its metabolite(Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 (if daily dosing) hours post dose; Cycle 1 Day 7, Cycle 2 Days 1 and 14 predose and 2 hours post dose; Cycle 3 Days 1 and 14 predose)
- Parts 2 and 3: Area under the curve from the time of dose to the last measurable concentration (AUClast) of sasanlimab(Through study completion, an average of 1 year)
- Parts 2 and 3: Maximum plasma concentration (Cmax) of sasanlimab(Through study completion, an average of 1 year)
- Parts 2 and 3: Time to reach maximum plasma concentration (Tmax) of sasanlimab(Through study completion, an average of 1 year)
- Part 3: Time to reach maximum plasma concentration at steady state (Tmax,ss) of axitinib(Each cycle is 21 days. Cycle 1 Day 1 predose; Cycle 1 Day 14 predose, 0.5,1,2,4, and 8 hours post dose)
- Parts 1, 2, and 3: Area under the curve from the time of dose to the last measurable concentration (AUClast) of PF-07265807 and its metabolite(Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 (if daily dosing) hours post dose; Cycle 1 Day 7, Cycle 2 Days 1 and 14 predose and 2 hours post dose; Cycle 3 Days 1 and 14 predose)
- Parts 2 and 3: Apparent clearance (CL/F) of sasanlimab(Through study completion, an average of 1 year)
- Parts 1, 2, and 3: Apparent terminal volume of distribution (Vz/F) of PF-07265807(Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 (if daily dosing) hours post dose; Cycle 1 Day 7, Cycle 2 Days 1 and 14 predose and 2 hours post dose; Cycle 3 Days 1 and 14 predose)
- Parts 2 and 3: Apparent terminal volume of distribution (Vz/F) of sasanlimab(Through study completion, an average of 1 year)
- Parts 1, 2, and 3: ORR(Baseline through approximately 2 years)
- Part 4: Number of participants with treatment emergent AEs(Baseline through approximately 2 years)
- Part 4: Number of participants with laboratory abnormalities(Baseline through approximately 2 years)
- Part 4: Trough concentration (Ctrough) of PF-07265807 and its metabolite(Each cycle is 21 days. Cycle 1 Days 1 and 14 predose, 2, 4 hours post dose; Cycle 1 Day 7 predose and 2 hours post dose; Cycle 2 Days 1 and 14 predose)
- Part 4: Post dose concentration (Cmax) of PF-07265807 and its metabolite(Each cycle is 21 days. Cycle 1 Days 1 and 14 predose, 2, 4 hours post dose; Cycle 1 Day 7 predose and 2 hours post dose; Cycle 2 Days 1 and 14 predose)
- Parts 1, 2, and 3: Maximum plasma concentration (Cmax) of PF-07265807 and its metabolite(Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 (if daily dosing) hours post dose; Cycle 1 Day 7, Cycle 2 Days 1 and 14 predose and 2 hours post dose; Cycle 3 Days 1 and 14 predose)
- Part 3: Area under the curve from the time of dose to the time of the subsequent dose (AUCtau) at steady state of axitinib(Each cycle is 21 days. Cycle 1 Day 1 predose; Cycle 1 Day 14 predose, 0.5,1,2,4, and 8 hours post dose)
- Parts 1, 2, and 3: Terminal elimination half-life (t1/2) of PF-07265807 and its metabolite(Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 (if daily dosing) hours post dose; Cycle 1 Day 7, Cycle 2 Days 1 and 14 predose and 2 hours post dose; Cycle 3 Days 1 and 14 predose)
- Parts 2 and 3: Terminal elimination half-life (t1/2) of sasanlimab(Through study completion, an average of 1 year)
- Parts 1, 2, and 3: Area under the curve from the time of dose extrapolated to infinity (AUCinf) of PF-07265807 and its metabolite(Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 (if daily dosing) hours post dose; Cycle 1 Day 7, Cycle 2 Days 1 and 14 predose and 2 hours post dose; Cycle 3 Days 1 and 14 predose)
- Parts 2 and 3: Area under the curve from the time of dose extrapolated to infinity (AUCinf) of sasanlimab(Through study completion, an average of 1 year)
- Parts 1, 2, and 3: Apparent oral clearance (CL/F) of PF-07265807(Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 (if daily dosing) hours post dose; Cycle 1 Day 7, Cycle 2 Days 1 and 14 predose and 2 hours post dose; Cycle 3 Days 1 and 14 predose)
- Parts 1, 2, and 3: Area under the curve from the time of dose to the time of the subsequent dose (AUCtau) at steady state of PF-07265807 and its metabolite(Each cycle is 21 days. Cycle 1 Days 1 and 14, predose, 0.5,1,2,4,8 and 24 (if daily dosing) hours post dose; Cycle 1 Day 7, Cycle 2 Days 1 and 14 predose and 2 hours post dose; Cycle 3 Days 1 and 14 predose)
- Parts 2, 3, and 4 Cohorts 2-4: Immunogenicity of sasanlimab when given in combination(Through study completion, an average of 1 year)
- Duration of Response(Baseline through approximately 2 years)
- Part 4, Cohorts 2, 3 and 4: Trough concentration (Ctrough) of sasanlimab(Each cycle is 21 days. Cycle 1 Days 1, 7, and 14, Cycle 2 Day 1, Cycle 7 Day 1, and every 6 cycles thereafter predose)
- Part 4, Cohort 4: Trough concentration (Ctrough) of axitinib(Each cycle is 21 days. Cycle 1 Day 1 predose; Cycle 1 Day 14 predose, 2, and 4 hours post dose)
- Progression Free Survival(Baseline through approximately 2 years)
- Disease Control Rate(Baseline through approximately 2 years)