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

Pfizer

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Diffuse Large B-Cell Lymphoma

Treatments: Drug: Lenalidomide; Drug: Maplirpacept; Drug: Tafasitamab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05626322

2022-502427-21-00 (Registry Identifier)

C4971003

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 6 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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6 participants in 2 patient groups

Phase 1b

Experimental group

Description:

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.

Treatment:

Drug: Tafasitamab

Drug: Maplirpacept

Drug: Lenalidomide

Phase 2

Experimental group

Description:

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).

Treatment:

Drug: Tafasitamab

Drug: Maplirpacept

Drug: Lenalidomide