Effects of Maplirpacept (PF-07901801),Tafasitamab, and Lenalidomide in People With Relapsed or Refractory Diffuse Large B-cell Lymphoma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Diffuse Large B-Cell Lymphoma

Intervention / Treatment
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* Drug: Maplirpacept
* Drug: Tafasitamab
* Drug: Lenalidomide


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 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 Key Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Open label/randomized
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1b<br>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. | Drug: Maplirpacept<br>* Intravenous infusion<br>* Other names: PF-07901801, TTI-622;Drug: Tafasitamab<br>* Intravenous infusion<br>* Other names: Minjuvi, Monjuvi;Drug: Lenalidomide<br>* Oral (by mouth)<br>* Other names: Revlimid;|
| Experimental: Phase 2<br>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). | Drug: Maplirpacept<br>* Intravenous infusion<br>* Other names: PF-07901801, TTI-622;Drug: Tafasitamab<br>* Intravenous infusion<br>* Other names: Minjuvi, Monjuvi;Drug: Lenalidomide<br>* Oral (by mouth)<br>* Other names: Revlimid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1b: Dose limiting toxicity (DLT) rate | DLTs are a predefined set of adverse events that are at least possibly related to any or all of the investigational agents. | 28 days following first dose | 
| Phase 2: Objective Response Rate (ORR) | OR defined as complete response or partial response as per Lugano Response Classification Criteria 2014 | Time from the date of first dose of study intervention until the first documentation of disease progression, death, or start of new anticancer therapy (assessed up to approximately 24 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1b and Phase 2: Frequency of adverse events (AE) | Type and severity (severity according to the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 5.0). | Time from the date of first dose of study intervention through 28 days after last dose of study intervention (assessed up to approximately 24 months) | 
| Phase 1b and Phase 2: Frequency of clinical laboratory abnormalities | Type and severity (severity according to the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 5.0). | Time from the date of first dose of study intervention through 28 days after last dose of study intervention (assessed up to approximately 24 months) | 
| Phase 1b: Objective Response Rate (ORR) | OR defined as complete response or partial response per Lugano Response Classification Criteria 2014 | Time from the date of first dose of study intervention until the first documentation of disease progression, death, or start of new anticancer therapy (assessed up to approximately 24 months) | 
| Phase 1b and Phase 2: Duration of Response (DoR) | CR and PR defined per Lugano Response Classification Criteria 2014 | Time from the first documentation of objective response until disease progression or death due to any cause, whichever occurs first (assessed up to approximately 24 months) | 
| Phase 1b and Phase 2: Complete Response Rate (CRR) | CR defined per Lugano Response Classification Criteria 2014 | Time from the date of first dose of study intervention until the first documentation of disease progression, death, or start of new anticancer therapy (assessed up to approximately 24 months) | 
| Phase 1b and Phase 2: Duration of Complete Response (DoCR) | CR defined per Lugano Response Classification Criteria 2014 | Time from the first documentation of a CR until PD, or death due to any cause, whichever occurs first (assessed up to approximately 24 months) | 
| Phase 1b and Phase 2: Progression Free Survival (PFS) | Progression defined per Lugano Response Classification Criteria 2014 | Time from the date of first dose of study intervention until PD, or death due to any cause, whichever occurs first (assessed up to approximately 24 months) | 
| Phase 1b and Phase 2: Pharmacokinetic parameters of PF-07901801 | Pre- and post-dose concentrations of PF-07901801 | On the first and 8th day of the first 28-day cycle, then the first day of every cycle through 6 cycles, then every third cycle through 13 cycles and every sixth cycle thereafter until end of treatment (assessed up to approximately 24 months) | 
| Phase 1b and Phase 2: Pharmacokinetic parameters of tafasitamab | Pre-dose concentrations of tafasitamab | On the first day of every 28-day cycle through 6 cycles, then every third cycle through 13 cycles and every sixth cycle thereafter until end of treatment (assessed up to approximately 24 months) | 
| Phase 1b and Phase 2: Pharmacokinetic parameters of of lenalidomide | Pre-dose concentrations of lenalidomide. | On the first first day of the first four 28-day cycles. | 
| Phase 1b and Phase 2: Incidence of Anti-Drug Antibody (ADA) against PF-07901801 | To evaluate immunogenicity of PF-07901801 | On the first day of every 28-day cycle through 6 cycles, then every third cycle through 13 cycles and every sixth cycle thereafter until end of treatment (assessed up to approximately 24 months) | 
| Phase 1b and Phase 2: Incidence of Anti-Drug Antibody (ADA) against tafasitamab | To evaluate immunogenicity of tafasitamab | On the first day of every 28-day cycle through 6 cycles, then every third cycle through 13 cycles and every sixth cycle thereafter until end of treatment (assessed up to approximately 24 months) | 
| Phase 1b and Phase 2: Neutralizing antibody (NAb) titers for PF-07901801 | To evaluate immunogenicity of PF-07901801 | On the first day of every 28-day cycle through 6 cycles, then every third cycle through 13 cycles and every sixth cycle thereafter until end of treatment (assessed up to approximately 24 months) | 
| Phase 1b and Phase 2: Neutralizing antibody (NAb) titers for tafasitamab | To evaluate immunogenicity of tafasitamab | On the first day of every 28-day cycle through 6 cycles, then every third cycle through 13 cycles and every sixth cycle thereafter until end of treatment (assessed up to approximately 24 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DLBCL, Lymphoma, Relapsed, Refractory, CD19, CD47, Maplirpacept, Tafasitamab, Lenalidomide