A Phase 1a/1b Dose-Escalation and Expansion Trial of TTI-622 in Patients With Advanced Hematologic Malignancies, Including Lymphoma, Leukemia, and Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Pfizer
- 入组人数
- 177
- 试验地点
- 61
- 主要终点
- Phase 1a: Number of adverse events (AE) by severity
研究概览
简要总结
The purpose of this clinical trial is to learn how the experimental medicine maplirpacept (PF-07901801) affects people with various types of blood cancers:
- relapsed or refractory (R/R) lymphoma
- multiple myeloma
- newly diagnosed acute myeloid leukemia (AML).
This trial will be conducted in the outpatient setting in 2 parts, phase 1a and phase 1b. You may only participate in one part of the study.
During phase 1a of this study, we will explore how much maplirpacept (PF-07901801), when used by itself, can be safely used.
If you have lymphoma, the study medicine maplirpacept (PF-07901801) will be given by infusion through a vein once a week or once every 2 weeks or every 3 weeks as determined by your doctor. Following your first dose, you will be expected to come back twice more the first week. From week 2, you will have weekly visits for blood tests, questions about your medications, any side effects, or illnesses you may have experienced and your cancer response. After you have completed 21 days (for every week dosing) or 42 days (for every 2- or 3-weeks dosing), your doctor will discuss whether you should stop study treatment or continue.
If you continue, you will be expected to come back weekly for blood tests, vital signs, a brief physical exam, asked about any side effects or illnesses you may have experienced and medications you may be taking. The dosing schedule you are assigned to will continue until your disease has worsened, significant side effects occur or other reasons that lead you and your doctor to decide treatment may be stopped.
To be eligible for the first part of the study you must be 18 years or older, your disease has worsened after receiving other medicines approved for blood cancer, no other treatment options exist for you, a sample of your tissue for exploratory research which can be taken from tissue already obtained or if necessary, a new sample of your tissue will be taken so your disease may be seen and measured on routine tests/scans. If you have had radiation therapy or received any anticancer medication within 14 days before the planned start of study treatment your doctor will let you know if you are eligible to participate in the study. If you have had major surgery within 30 days before the planned start of study treatment you may not be eligible to participate.
The phase 1a part of the study may last up to 51/2 years. How long you participate in this study depends on side effects you may have to the study drug. It also depends on how your cancer responds to the study drug. Therefore, you may remain in the study as long as you and your study doctor think you may benefit. However, you are free to stop taking part in this study at any time and for any reason.
During phase 1b part of this study, we will explore how much maplirpacept (PF-07901801), when used with other anticancer medicine(s), can be safe and reduce cancer growth. In the phase 1b part of this study, you will receive maplirpacept (PF-07901801) and other anticancer medicine(s). Which medicine combination you will receive depends on the types of cancer under treatment. Your treatment experiences will be examined to determine if maplirpacept (PF-07901801) when given with other anticancer medicine(s), is safe and can reduce cancer growth.
To be eligible for the second part of the study you may have newly diagnosed Acute Myelocytic Leukemia with or without a genetic mutation or you have Multiple Myeloma or Diffuse Large B Cell Lymphoma, and your disease has worsened.
The Phase 1b part of this study may last as long as you and your study doctor think you may benefit which could be up to approximately 31/2 years. How long you participate in this study depends on side effects you may have to the study drug. It also depends on how your cancer responds to the study drug. Therefore, you may remain in the study as long as you and your study doctor think you may benefit. However, you are free to stop taking part in this study at any time and for any reason.
详细描述
This is a trial of maplirpacept (PF-07901801) in subjects with relapsed or refractory lymphoma or multiple myeloma (MM) and subjects with newly diagnosed acute myeloid leukemia (AML).
This trial will be conducted in 2 phases: Phase 1a (Dose-Escalation Phase for Single-Agent maplirpacept (PF-07901801) and Phase 1b maplirpacept (PF-07901801) Combinations and Single-Agent.
In the Dose-Escalation Phase for Single-Agent maplirpacept (PF-07901801), subjects with relapsed or refractory lymphoma will be enrolled in sequential dose cohorts.
In the Combination and Single-Agent Treatment part, subjects will be included in 1 of 14 cohorts: (Cohort A1 and A2) subjects with newly diagnosed TP53-mutated AML will be treated with maplirpacept (PF-07901801) + azacitidine; (Cohort B1 and B2) elderly subjects or subjects unfit for intensive induction chemotherapies with newly diagnosed TP53-wildtype AML will be treated with maplirpacept (PF-07901801) + azacitidine and venetoclax; (Cohort C1, C2, and C3) subjects with relapsed or refractory MM will be treated with maplirpacept (PF-07901801) + carfilzomib and dexamethasone;(Cohort D1 and D2) subjects in relapsed or refractory CD20+ diffuse large B-cell lymphoma will be treated with maplirpacept (PF-07901801) + an anti-CD20 targeting agent; (Cohort E1 and E2) subjects with relapsed refractory MM will be treated with single-agent maplirpacept (PF-07901801); and (Cohorts F1, F2 and F3) with relapsing or refractory MM will be treated with increasing doses of maplirpacept (PF-07901801) + isatuximab, carfilzomib and dexamethasone.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
maplirpacept (PF-07901801) Monotherapy
In the phase 1a dose- escalation part for single-agent maplirpacept (PF-07901801), participants with Relapsing or Refractory (R/R) lymphoma will be enrolled in sequential dose cohorts to receive maplirpacept (PF-07901801) QW to characterize safety, tolerability, and PK; to determine the Maximum Tolerated Dose (MTD) or P1b Starting Dose (a dose lower than or equal to the single-agent MTD), and to gain preliminary evidence of antitumor activity.
In addition, participants with R/R Lymphoma may also be enrolled in a cohort to receive maplirpacept (PF-07901801) Q2W and a cohort to receive maplirpacept (PF-07901801) Q3W to characterize safety, tolerability, and PK; to determine the MTD; and to gain preliminary evidence of antitumor activity.
干预措施: Maplirpacept (PF-07901801) (Drug)
Cohort A: maplirpacept (PF-07901801) + Azacitidine
Cohort A1: participants with newly diagnosed TP53-mutated Acute Myelocytic Leukemia (AML) will be treated with maplirpacept (PF-07901801) QW + azacitidine.
Cohort A2: participants with newly diagnosed TP53-mutated AML will be treated with maplirpacept (PF-07901801) QW + azacitidine.
干预措施: Maplirpacept (PF-07901801) (Drug)
Cohort A: maplirpacept (PF-07901801) + Azacitidine
Cohort A1: participants with newly diagnosed TP53-mutated Acute Myelocytic Leukemia (AML) will be treated with maplirpacept (PF-07901801) QW + azacitidine.
Cohort A2: participants with newly diagnosed TP53-mutated AML will be treated with maplirpacept (PF-07901801) QW + azacitidine.
干预措施: Azacitidine (Drug)
Cohort B: maplirpacept (PF-07901801) + Azacitidine and Venetoclax
Cohort B1: elderly or unfit participants with newly diagnosed TP53-wildtype AML will be treated with maplirpacept (PF-07901801) QW + azacitidine and venetoclax
Cohort B2: elderly or unfit participants with newly diagnosed TP53-wildtype AML will be treated with maplirpacept (PF-07901801) QW + azacitidine and venetoclax.
干预措施: Maplirpacept (PF-07901801) (Drug)
Cohort B: maplirpacept (PF-07901801) + Azacitidine and Venetoclax
Cohort B1: elderly or unfit participants with newly diagnosed TP53-wildtype AML will be treated with maplirpacept (PF-07901801) QW + azacitidine and venetoclax
Cohort B2: elderly or unfit participants with newly diagnosed TP53-wildtype AML will be treated with maplirpacept (PF-07901801) QW + azacitidine and venetoclax.
干预措施: Azacitidine (Drug)
Cohort B: maplirpacept (PF-07901801) + Azacitidine and Venetoclax
Cohort B1: elderly or unfit participants with newly diagnosed TP53-wildtype AML will be treated with maplirpacept (PF-07901801) QW + azacitidine and venetoclax
Cohort B2: elderly or unfit participants with newly diagnosed TP53-wildtype AML will be treated with maplirpacept (PF-07901801) QW + azacitidine and venetoclax.
干预措施: Venetoclax (Drug)
Cohort D1 and D2: maplirpacept (PF-07901801) + an anti-CD20 targeting agent
Cohort D1: participants with Relapsing or Recurrent (R/R) CD20+ Diffuse Large B Cell Lymphoma (DLBCL) will be treated with maplirpacept (PF-07901801) QW, then an increased dose Q3W + an anti-CD20 targeting agent.
Cohort D2: participants with R/R CD20+ DLBCL will be treated with maplirpacept (PF-07901801) dosed QW for 4 weeks, then an increased dose Q3W + an anti-CD20 targeting agent.
干预措施: Maplirpacept (PF-07901801) (Drug)
Cohort D1 and D2: maplirpacept (PF-07901801) + an anti-CD20 targeting agent
Cohort D1: participants with Relapsing or Recurrent (R/R) CD20+ Diffuse Large B Cell Lymphoma (DLBCL) will be treated with maplirpacept (PF-07901801) QW, then an increased dose Q3W + an anti-CD20 targeting agent.
Cohort D2: participants with R/R CD20+ DLBCL will be treated with maplirpacept (PF-07901801) dosed QW for 4 weeks, then an increased dose Q3W + an anti-CD20 targeting agent.
干预措施: Anti-CD20 Targeting agent (Drug)
Cohort E1 and E2: single agent maplirpacept (PF-07901801)
Cohort E1: participants with Relapsing or Recurrent (R/R) Multiple Myeloma (MM) will be treated with single agent maplirpacept (PF-07901801) QW.
Cohort E2: participants with R/R MM will be treated with single agent maplirpacept (PF-07901801) increased dose QW.
干预措施: Maplirpacept (PF-07901801) (Drug)
Cohort F1, F2 and F3: maplirpacept (PF-07901801) + isatuximab, carfilzomib and dexamethasone
Cohort F1: participants with Relapsing or Recurrent (R/R) Multiple Myeloma (MM) will be treated with increasing doses of maplirpacept (PF-07901801) + isatuximab, carfilzomib and dexamethasone.
Cohort F2: participants with R/R MM will be treated with maplirpacept (PF-07901801) QW + isatuximab, carfilzomib and dexamethasone.
Cohort F3: participants with R/R MM will be treated with maplirpacept (PF-07901801) increased dose QW + isatuximab, carfilzomib and dexamethasone.
干预措施: Maplirpacept (PF-07901801) (Drug)
Cohort F1, F2 and F3: maplirpacept (PF-07901801) + isatuximab, carfilzomib and dexamethasone
Cohort F1: participants with Relapsing or Recurrent (R/R) Multiple Myeloma (MM) will be treated with increasing doses of maplirpacept (PF-07901801) + isatuximab, carfilzomib and dexamethasone.
Cohort F2: participants with R/R MM will be treated with maplirpacept (PF-07901801) QW + isatuximab, carfilzomib and dexamethasone.
Cohort F3: participants with R/R MM will be treated with maplirpacept (PF-07901801) increased dose QW + isatuximab, carfilzomib and dexamethasone.
干预措施: Carfilzomib (Drug)
Cohort F1, F2 and F3: maplirpacept (PF-07901801) + isatuximab, carfilzomib and dexamethasone
Cohort F1: participants with Relapsing or Recurrent (R/R) Multiple Myeloma (MM) will be treated with increasing doses of maplirpacept (PF-07901801) + isatuximab, carfilzomib and dexamethasone.
Cohort F2: participants with R/R MM will be treated with maplirpacept (PF-07901801) QW + isatuximab, carfilzomib and dexamethasone.
Cohort F3: participants with R/R MM will be treated with maplirpacept (PF-07901801) increased dose QW + isatuximab, carfilzomib and dexamethasone.
干预措施: Dexamethasone (Drug)
Cohort F1, F2 and F3: maplirpacept (PF-07901801) + isatuximab, carfilzomib and dexamethasone
Cohort F1: participants with Relapsing or Recurrent (R/R) Multiple Myeloma (MM) will be treated with increasing doses of maplirpacept (PF-07901801) + isatuximab, carfilzomib and dexamethasone.
Cohort F2: participants with R/R MM will be treated with maplirpacept (PF-07901801) QW + isatuximab, carfilzomib and dexamethasone.
Cohort F3: participants with R/R MM will be treated with maplirpacept (PF-07901801) increased dose QW + isatuximab, carfilzomib and dexamethasone.
干预措施: Isatuximab (Drug)
Cohort C1, C2 and C3: maplirpacept (PF-07901801) + Carfilzomib and Dexamethasone
Cohort C1: participants with Relapsing or Refractory (R/R) Multiple Myeloma (MM) will be treated with maplirpacept (PF-07901801) QW
- carfilzomib and dexamethasone.
Cohort C2: participants with R/R MM will be treated with maplirpacept (PF-07901801) QW + carfilzomib and dexamethasone.
Cohort C3: participants with R/R MM will be treated with maplirpacept (PF-07901801) Q2W + carfilzomib and dexamethasone.
干预措施: Maplirpacept (PF-07901801) (Drug)
Cohort C1, C2 and C3: maplirpacept (PF-07901801) + Carfilzomib and Dexamethasone
Cohort C1: participants with Relapsing or Refractory (R/R) Multiple Myeloma (MM) will be treated with maplirpacept (PF-07901801) QW
- carfilzomib and dexamethasone.
Cohort C2: participants with R/R MM will be treated with maplirpacept (PF-07901801) QW + carfilzomib and dexamethasone.
Cohort C3: participants with R/R MM will be treated with maplirpacept (PF-07901801) Q2W + carfilzomib and dexamethasone.
干预措施: Carfilzomib (Drug)
Cohort C1, C2 and C3: maplirpacept (PF-07901801) + Carfilzomib and Dexamethasone
Cohort C1: participants with Relapsing or Refractory (R/R) Multiple Myeloma (MM) will be treated with maplirpacept (PF-07901801) QW
- carfilzomib and dexamethasone.
Cohort C2: participants with R/R MM will be treated with maplirpacept (PF-07901801) QW + carfilzomib and dexamethasone.
Cohort C3: participants with R/R MM will be treated with maplirpacept (PF-07901801) Q2W + carfilzomib and dexamethasone.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Phase 1a: Number of adverse events (AE) by severity
时间窗: Through study completion, up to 18 months
To characterize the safety profile (incidence of AEs)
Phase 1a: Number of AEs by Frequency
时间窗: Through study completion, up to 18 months
To characterize the safety profile (incidence of AEs) and
Phase 1a: Number of participants with Dose-Limiting Toxicities (DLT)
时间窗: Up to 21-42 days
To characterize the dose limiting toxicities (DLTs) of TTI-622.
Phase 1b: Number of adverse events (AE) by severity
时间窗: Through study completion, up to 30 months
To characterize the safety profile (incidence of AEs) of TTI-622 given in combinations or as a single agent.
Phase 1b: Number of adverse events (AE) by frequency
时间窗: Through study completion, up to 30 months
To characterize the safety profile (incidence of AEs) of TTI-622 given in combination or as a single agent.
Phase 1b: Number of participants with disease response
时间窗: Through study completion, up to 30 months
To evaluate response rate of each combination treatment in the (7) combination cohorts (A1,A2, B1, B2, C1, C2, C3, D1, D2, F1, F2, F3) and for single agent treatment (Cohort E1 and E2). For AML, response = CR. For MM, response = CR+sCR+VGBR+PR. For DLBCL, OR=CR+PR
Phase 1a: Maximum Tolerated Dose (MTD)
时间窗: Baseline (the start of each sequentially increased treatment dose), up to the 3rd evaluable patient completes DLT observation period of 21 or 42 days.
To characterize the highest dose level for which no more than 1 participant in a dose cohort experienced DLTs.
Phase 1b: Recommended dose of TTI-622 in combination with selected anticancer treatments
时间窗: Through study completion, up to 30 months
To characterize the recommended dose of TTI-622 in combination with selected anticancer treatments in 5 patient populations: * TTI-622 plus azacitidine in newly diagnosed TP53-mutated AML * TTI-622 plus azacitidine and venetoclax in elderly (\>/= 75 years old) or unfit, newly diagnosed TP53-wildtype AML * TTI-622 plus Carfilzomib and dexamethasone in Carfilzomib-refractory, Relapsed/Refractory (R/R) multiple myeloma (MM) after 3 or more prior lines of therapy * TTI-622 plus an anti-CD20 targeting agent (such as ruxience or rituxan) in R/R CD20+ DLBCL after 1 or more prior lines of therapy * TTI-622 plus isatuximab, carfilzomib and dexamethasone in R/R MM after 1-3 prior lines of therapy
Phase 1b: Recommended dose of TTI-622 as a single agent
时间窗: Through study completion, up to 30 months
To characterize the recommended dose of TTI-622 as a single agent in patients with R/R MM after 3 or more prior lines of therapy.
Number of participants with response assessments that show preliminary efficacy
时间窗: Through study completion, up to 30 months
To evaluate preliminary efficacy of each combination treatment in the selected patient populations and for single-agent treatment in R/R MM
次要结局
- Phase 1a: TTI-622 PK parameter AUC0-t(Through study completion, up to 18 months)
- Phase 1a: TTI-622 PK parameter Cmax(Through study completion, up to 18 months)
- Phase 1a: Incidence of anti-drug antibodies (ADA)(Through study completion, up to 18 months)
- Phase 1a: Number of participants with overall response rate (ORR) for participants treated with TTI-622.(Through study completion, up to 18 months)
- Phase 1a: Number of participants with disease control rate (DCR)(Through study completion, up to 18 months)
- Phase 1a: Time to response (TTR)(Through study completion, up to 18 months)
- Phase 1a: Duration of Response (DR)(Through study completion, up to 18 months)
- Phase 1a: Progression free survival (PFS)(Through study completion, up to 18 months)
- Phase 1b: TTI-622 PK parameter Cmax when combined with selected anticancer treatments or as a single agent(Through study completion, up to 30 months)
- Phase 1b: incidence of anti-drug antibodies (ADA) Immunogenicity of TTI-622 when combined with selected anticancer treatments or as a single agent(Through study completion, up to 30 months)
- Phase 1b: Number of participants with disease control rate (DCR)(Through study completion, up to 30 months)
- Phase 1b: Time to response (TTR)(Through study completion, up to 30 months)
- Phase 1b: Event-free survival (EFS)(Through study completion, up to 30 months)
- Phase 1b: Duration of response (DR)(Through study completion, up to 30 months)
- Phase 1b: Progression-free survival (PFS)(Through study completion, up to 30 months)
- Phase 1b: Number of Participants With Minimal Residual Disease Burden (MRD) Positive, Negative and Not Evaluable (NE) Status(Through study completion, up to 30 months)