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

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

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.

Study Overview

• Status: Terminated
• Conditions: Diffuse Large B-Cell Lymphoma
• Intervention / Treatment: Drug: Tafasitamab; Drug: Lenalidomide; Drug: Maplirpacept

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Yamagata, Japan, 990-9585
    • Yamagata University Hospital
• South Korea
  • Pusan-kwangyǒkshi
    • Busan, Pusan-kwangyǒkshi, South Korea, 49201
      • Dong-A University Hospital
  • Seoul-teukbyeolsi [seoul]
    • Seoul, Seoul-teukbyeolsi [seoul], South Korea, 03080
      • Seoul National University Hospital
• United States
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Mary Bird Perkins Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital
    • Providence, Rhode Island, United States, 02903
      • Lifespan Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Tafasitamab; Intravenous infusion; Other Names: Minjuvi, Monjuvi; Drug: Lenalidomide; Oral (by mouth); Other Names: Revlimid; Drug: Maplirpacept; Intravenous infusion; Other Names: PF-07901801, TTI-622
Experimental: 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).	Drug: Tafasitamab; Intravenous infusion; Other Names: Minjuvi, Monjuvi; Drug: Lenalidomide; Oral (by mouth); Other Names: Revlimid; Drug: Maplirpacept; Intravenous infusion; Other Names: PF-07901801, TTI-622

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs)	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.	Cycle 1 (28 Days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs are those events with onset dates occurred during the on-treatment period for the first time, or if the worsening of an event is during the on-treatment period.	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	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/ incapacity, was a congenital anomaly/birth defect or other important medical event. TEAEs are those events with onset dates occurred during the on-treatment period for the first time, or if the worsening of an event is during the on-treatment period.	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	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Related AEs were those related to any study drug (i.e., at least one of the study drugs) reported by the investigator.	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	The following hematological parameters were assessed: anemia, hemoglobin increased, leukocytosis, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, and white blood cell (WBC) decreased. Lab abnormalities were graded according to National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) version (v) 5.0 where Grade 0= no AE, Grade 1= mild AE, Grade 2 =moderate AE, Grade 3= severe AE, and Grade 4= life-threatening consequences; urgent intervention indicated. Only those parameters with at least 1 non-zero data values showing any shift in grades from Baseline to any time post-baseline in any reporting group were reported in this outcome measure. Participants whose grade category was unchanged (e.g. Grade 0 to Grade 0) were not reported.	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	The following clinical chemistry parameters were assessed: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hypercalcemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia and hyponatremia. Lab abnormalities were graded according to NCI CTCAE v5.0 where Grade 0= no AE, Grade 1=mild AE, Grade 2 = moderate AE, Grade 3 =severe AE, and Grade 4 =life-threatening consequences; urgent intervention indicated. Only those parameters with at least 1 non-zero data values showing any shift in grades from Baseline to any time post-baseline in any reporting group were reported in this outcome measure. Participants whose grade category was unchanged (e.g. Grade 0 to Grade 0) were not reported.	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	OR:best overall response (BOR) of complete response (CR) or partial response (PR) per Lugano Response Classification Criteria 2014 as determined by investigator. CR:positron emission tomography-computed tomography (PET-CT) score 1 (complete metabolic response), 2 (likely benign), or 3 (uncertain significance) with or without a residual mass on Deauville five-point scale ([5PS] standardized scoring system used to evaluate the extent of disease activity in patients with lymphoma through PET scans, ranging from 1 to 5, higher scores indicates more disease activity) or on computed tomography (CT),target nodes/nodal masses regressed to <=1.5 centimeter (cm) in longest diameter (LDi). PR:PET-CT score 4 (possible residual disease) or 5 (progressive disease) with reduced uptake compared with baseline and residual mass(es) of any size or On CT >=50% decrease in sum of the product of the diameters (SPD) of up to 6 target measurable nodes and extra nodal sites. 95% CI was based on Wilson method.	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	DoR: time from first documentation of OR until PD, or death due to any cause, whichever occurred first. DoR was censored on date of last adequate disease assessment for participants without an event. OR=BOR of CR or PR,CR=PET-CT score 1,2,or 3 with/without a residual mass on Deauville five-point scale(1 to 5,higher scores=more disease activity)or on CT,target nodes/nodal masses regressed to <=1.5cm in LDi. PR:PET-CT score 4 or 5 with reduced uptake compared with baseline and residual mass of any size or On CT >=50% decrease in SPD of up to 6 target measurable nodes and extra nodal sites. PD:PET-CT score 4 or 5 with increase in intensity of uptake from baseline and/or new fluorodeoxyglucose (FDG)-avid foci consistent with lymphoma at interim or end-of-treatment assessment or on CT,an individual abnormal node/lesion with: LDi>1.5cm and increase by >=50% from product of perpendicular diameters nadir and increase in LDi or SDi from nadir 0.5cm for lesions <=2cm and 1.0cm for lesions >2cm.	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	CR as per Lugano Response Classification Criteria 2014 as assessed by the investigator was defined as: PET-CT score 1 (complete metabolic response), 2 (likely benign), or 3 (uncertain significance) with or without a residual mass on 5PS (standardized scoring system used to evaluate the extent of disease activity in patients with lymphoma through PET scans, ranging from 1 to 5, higher scores indicates more disease activity) or on CT, target nodes/nodal masses regressed to <=1.5 cm in LDi.	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	DoCR:time from first documentation of CR until PD,or death, whichever occurred first. CR:PET-CT 1(complete metabolic response),2(likely benign),3(uncertain significance)with or without residual mass on 5PS(scale from 1 to 5,higher scores=more disease activity)/CT,target nodes/nodal masses regressed <=1.5cm in LDi.PD:PET-CT 4(possible residual disease)or 5(PD)with increase intensity of uptake and new FDG-avid foci consistent with lymphoma at interim/EOT assessment/CT,individual abnormal node/lesion with:LDi >1.5cm and increase >=50% from PPD nadir, increase in LDi or SDi from nadir 0.5cm for lesions <=2cm and 1.0cm for lesions >2cm. DoCR censored on date of last adequate assessment for participants without an event on date of last adequate disease assessment before new anti-cancer therapy if new anti-cancer therapy started prior to event,date of last adequate disease assessment before 2 or more missing disease assessments for participants with event after 2 or more missing assessments.	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	PFS: time from date of first dose until PD per Lugano Response Classification Criteria 2014 or death due to any cause,whichever occurred first.Participants without any event,censored on date of last adequate disease assessment;participants with new anticancer therapy prior to an event,censored on date of last disease assessment before new anticancer therapy;participants with an event after a gap of 2 or more missing disease assessments,censored on date of last disease assessment before gap;participants without an adequate post-baseline disease assessment were censored on date of first dose of study intervention unless death occurred on or before time of second planned disease assessment in which case death was considered an event.PD:PET-CT score 4 or 5 with increase in intensity of uptake from baseline and/or new FDG or LDi>1.5cm and increase by >=50% from product of perpendicular diameters nadir and increase in LDi or SDi from nadir 0.5cm for lesions <=2cm and 1.0cm for lesions >2cm.	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	All concentrations assayed below the level of quantification (BLQ) were set to 0 and their data is not reported in this outcome measure.	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	Number of participants with ADA and NAb against PF-07901801 were reported in this outcome measure. A participant was ADA (or NAb) positive if: (1) baseline titer was missing or negative and participant had >= 1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a >= 4-folder dilution increase in titer from baseline in >= 1 post-treatment sample (treatment-boosted).	From first dose of the study treatment (Day 1) up to end of study treatment (maximum up to 14.2 months)

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Incyte Corporation; MorphoSys AG
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2023
• Primary Completion (Actual): August 12, 2024
• Study Completion (Actual): May 1, 2025

Study Registration Dates

• First Submitted: November 15, 2022
• First Submitted That Met QC Criteria: November 15, 2022
• First Posted (Actual): November 23, 2022

Study Record Updates

• Last Update Posted (Estimated): September 5, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: DLBCL; Lymphoma; Relapsed; Refractory; Lenalidomide; CD19; CD47; Tafasitamab; Maplirpacept
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Piperidines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; tafasitamab
• Other Study ID Numbers: C4971003; 2022-502427-21-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No