A PHASE 1b/2 STUDY OF PF-07901801, A CD47 BLOCKING AGENT, WITH TAFASITAMAB AND LENALIDOMIDE FOR PARTICIPANTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA NOT ELIGIBLE FOR STEM CELL TRANSPLANTATION
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 6
- 试验地点
- 7
- 主要终点
- Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to learn about the effects of three study medicines [maplirpacept (PF-07901801), tafasitamab, and lenalidomide] when given together for the treatment of diffuse large B-cell lymphoma (DLBCL) that:
- is relapsed (has returned after last treatment) or
- is refractory (has not responded to last treatment)
DLBCL is a type of non-Hodgkin lymphoma (NHL). NHL is a cancer of the lymphatic system. It develops when the body makes abnormal lymphocytes. These lymphocytes are a type of white blood cell that normally help to fight infections.
This study is seeking participants who are unable or unwilling to undergo an autologous stem cell transplantation (when doctors put healthy blood cells back into your body) or CAR-T immune cell therapy.
Everyone in this study will receive three medicines: maplirpacept (PF-07901801), tafasitamab and lenalidomide. Participants will receive maplirpacept (PF-07901801) and tafasitamab at the study clinic by intravenous (IV) infusion (given directly into a vein) and lenalidomide will be taken by mouth at home. Study interventions will be administered in 28-day cycles. Maplirpacept (PF-07901801) will be given weekly for the first three cycles and then every two weeks. Tafasitamab will administered on Days 1, 4, 8, 15 and 22 in cycle 1, weekly in cycles 2 and 3 and then every 2 weeks in cycle 4 and beyond. Lenalidomide will be taken every day for Days 1 to 21 of each 28-day cycle for the first 12 cycles.
Participants can continue to take maplirpacept (PF-07901801) and tafasitamab until their lymphoma is no longer responding. Lenalidomide is discontinued after 12 cycles.
Maplirpacept (PF-07901801) will be given at different doses to different participants. Everyone taking part will receive approved doses of tafasitamab and lenalidomide. We will compare the experiences of people receiving different doses of PF-07901801. This will help us to determine what dose is safe and effective when combined with the other 2 study medicines.
详细描述
This is a multicenter, open-label, Phase 1b/2 study to evaluate the safety, tolerability and potential clinical benefits of maplirpacept (PF-07901801), an anti-CD47 molecule, in combination with standard doses of tafasitamab and lenalidomide in participants with relapsed/refractory (R/R) DLBCL not eligible for or unwilling to undergo high dose chemotherapy and subsequent autologous stem cell transplantation (ASCT) or unable to receive approved chimeric antigen receptor T-cell (CAR-T) therapy (for example, due to logistical limitations).
For Phase 1b, participants must have previously received at least 1 prior systemic treatment regimen. For Phase 2, participants must have received at least 1 but no more than 2 prior systemic treatment regimens. All participants must have previously received an anti-CD20 containing regimen.
Phase 1b will assess dose-limiting toxicities of maplirpacept (PF-07901801) when administered in combination with tafasitamab and lenalidomide, to select up to 2 doses for the Phase 2 part of the study. Phase 2 will evaluate safety and efficacy to determine the recommended Phase 3 dose of Maplirpacept (PF-07901801) to be administered in combination with tafasitamab and lenalidomide.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Histologically confirmed diagnosis of DLBCL
- •Relapsed or refractory disease
- •Participant is not be a candidate for or is unwilling to undergo high dose chemotherapy and subsequent stem cell transplant and/or is unable to receive chimeric antigen receptor (CAR) T-cell therapy
- •Previous treatment with at least one prior line of systemic therapy (for phase 2, at least 1 and no more than 2 prior lines of systemic therapy). Prior therapy must include an anti-CD20 antibody.
- •Adequate bone marrow, hepatic and renal function
- •Eastern Cooperative Oncology Group (ECOG) ≤2
- •Must provide a tumor tissue sample (fresh or archival, collected prior to start of treatment) for biomarker analysis
排除标准
- •Prior treatment with an anti-CD47 or anti-CD19 (other than CAR T) or immunomodulatory agents
- •Prior allogeneic stem cell transplantation or autologous stem cell transplantation within 12 weeks prior to enrolment
- •Participants with active, uncontrolled bacterial, fungal or viral infection.
研究组 & 干预措施
Phase 1b
Participants will be allocated to sequential dose levels of maplirpacept (PF-07901801), administered in combination with standard doses of tafasitamab and lenalidomide, to select two doses for further evaluation in Phase 2. Approximately 20 participants will be enrolled.
干预措施: Maplirpacept (Drug)
Phase 1b
Participants will be allocated to sequential dose levels of maplirpacept (PF-07901801), administered in combination with standard doses of tafasitamab and lenalidomide, to select two doses for further evaluation in Phase 2. Approximately 20 participants will be enrolled.
干预措施: Tafasitamab (Drug)
Phase 1b
Participants will be allocated to sequential dose levels of maplirpacept (PF-07901801), administered in combination with standard doses of tafasitamab and lenalidomide, to select two doses for further evaluation in Phase 2. Approximately 20 participants will be enrolled.
干预措施: Lenalidomide (Drug)
Phase 2
Participants will be randomized to 1 of 2 different dose levels of maplirpacept (PF-07901801) which will be administered in combination with standard doses of tafasitamab and lenalidomide. Approximately 50 participants will be enrolled (25 per dose).
干预措施: Maplirpacept (Drug)
Phase 2
Participants will be randomized to 1 of 2 different dose levels of maplirpacept (PF-07901801) which will be administered in combination with standard doses of tafasitamab and lenalidomide. Approximately 50 participants will be enrolled (25 per dose).
干预措施: Tafasitamab (Drug)
Phase 2
Participants will be randomized to 1 of 2 different dose levels of maplirpacept (PF-07901801) which will be administered in combination with standard doses of tafasitamab and lenalidomide. Approximately 50 participants will be enrolled (25 per dose).
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: Cycle 1 (28 Days)
DLTs included: Hematological: Grade (G) 4 thrombocytopenia (\<25,000/microliter \[mcL\]) lasting \>=72 hours or a platelet count \<=10,000/mcL at any time, unexplained by underlying disease; \>=G3 thrombocytopenia associated with \>=G2 bleeding, unexplained by underlying disease. G4 anemia; unexplained by underlying disease; G4 neutropenia lasting \>=7 days, unexplained by underlying disease; G3 febrile (\>38.3-degree Celsius \[C\]) neutropenia lasting \>=7 days, unexplained by underlying disease; G4 febrile neutropenia unexplained by underlying disease. Non-hematological: any treatment-related \>=G3 non-hematologic toxicity; Other \>=G2 PF-07901801-related non-hematologic toxicities that, in the opinion of the investigator, required a dose reduction or discontinuation of PF-07901801 were considered a DLT.
次要结局
- Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs)(From Day 1 of dosing up to 35 days post last dose of PF-07901801 and/or lenalidomide or 90 days after the last dose of tafasitamab, whichever was longer (maximum up to 14.2 months of exposure))
- Phase 1b: Number of Participants With Serious Treatment Emergent Adverse Events(From Day 1 of dosing up to 35 days post last dose of PF-07901801 and/or lenalidomide or 90 days after the last dose of tafasitamab, whichever was longer (maximum up to 14.2 months of exposure))
- Phase 1b: Number of Participants With Treatment-Related AEs(From Day 1 of dosing up to 35 days post last dose of PF-07901801 and/or lenalidomide or 90 days after the last dose of tafasitamab, whichever was longer (maximum up to 14.2 months of exposure))
- Phase 1b: Number of Participants With Grade Shift From Baseline in Hematology Parameters to Any Time Post-baseline(From baseline (latest non-missing value from pre-treatment period) up to 35 days post last dose of PF-07901801 and/or lenalidomide or 90 days after the last dose of tafasitamab, whichever was longer (maximum up to 14.2 months of exposure))
- Phase 1b: Number of Participants With Grade Shift From Baseline in Chemistry Parameters to Any Time Post Baseline(From baseline (latest non-missing value from pre-treatment period) up to 35 days post last dose of PF-07901801 and/or lenalidomide or 90 days after the last dose of tafasitamab, whichever was longer (maximum up to 14.2 months of exposure))
- Phase 1b: Percentage of Participants With Objective Response (OR) as Per Lugano Response Classification Criteria 2014 as Assessed by the Investigator(From date of first dose until first documentation of disease progression (PD), death or start of new anticancer therapy, whichever occurred first (maximum up to 14.2 months))
- Phase 1b: Duration of Response (DoR) as Per Lugano Response Classification Criteria 2014 as Assessed by the Investigator(From first documentation of OR until PD or death due to any cause whichever occurred first or date of censoring (maximum up to 14.2 months))
- Phase 1b: Percentage of Participants With CR as Per Lugano Response Classification Criteria 2014 as Assessed by the Investigator(From date of first dose until first documentation of CR (maximum up to 14.2 months))
- Phase 1b: Duration of Complete Response (DoCR) as Per Lugano Response Classification Criteria 2014 as Assessed by the Investigator(From time of first documentation of CR until PD, or death due to any cause, whichever occurred first or date of censoring (maximum up to 14.2 months))
- Phase 1b: Progression Free Survival (PFS) as Per Lugano Response Classification Criteria 2014 as Assessed by the Investigator(From date of first dose until PD or death due to any cause, whichever occurred first or censoring date (maximum up to 14.2 months))
- Phase 1b: Plasma Concentration of PF-07901801(Cycle 1 and 2 Day 1: Predose, 1 Hour (H) and 5H post dose; Cycle 1 Day 8: pre-dose, Day 1 of Cycles 3, 4, 5, 7, 10 and 13: Predose)
- Phase 1b: Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (NAb) Against PF-07901801(From first dose of the study treatment (Day 1) up to end of study treatment (maximum up to 14.2 months))