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: Recruiting
• 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 (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Locations

• Japan
  • Fukuoka, Japan, 812-8582
    • Not yet recruiting
    • Kyushu University Hospital
  • Yamagata, Japan, 990-9585
    • Recruiting
    • Yamagata University Hospital
  • Tokyo
    • Koto, Tokyo, Japan, 135-8550
      • Not yet recruiting
      • Japanese Foundation for Cancer Research
    • Koto, Tokyo, Japan, 135-8550
      • Not yet recruiting
      • The Cancer Institute Hospital of JFCR
• Korea, Republic of
  • Pusan-kwangyǒkshi
    • Busan, Pusan-kwangyǒkshi, Korea, Republic of, 49201
      • Recruiting
      • Dong-A University Hospital
  • Seoul-teukbyeolsi [seoul]
    • Seoul, Seoul-teukbyeolsi [seoul], Korea, Republic of, 03080
      • Not yet recruiting
      • Seoul National University Hospital
• Puerto Rico
  • San Juan, Puerto Rico, 00918
    • Recruiting
    • Auxilio Mutuo Cancer Center
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Winship Cancer Institute
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Recruiting
      • Mary Bird Perkins Cancer Center
    • Baton Rouge, Louisiana, United States, 70805
      • Recruiting
      • LSU Health Baton Rouge North Clinic
    • Baton Rouge, Louisiana, United States, 70808
      • Recruiting
      • Our Lady of the Lake Physician Group-Medical Oncology
    • Baton Rouge, Louisiana, United States, 70809
      • Recruiting
      • Our Lady of the Lake RMC
    • Baton Rouge, Louisiana, United States, 70808
      • Recruiting
      • Our Lady of the Lake RMC
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Recruiting
      • The Miriam Hospital
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Lifespan Cancer Institute
  • Tennessee
    • Knoxville, Tennessee, United States, 37916
      • Recruiting
      • Thompson Cancer Survival Center
    • Knoxville, Tennessee, United States, 37916
      • Not yet recruiting
      • Thompson Cancer Survival Center
    • Knoxville, Tennessee, United States, 37932
      • Recruiting
      • Thompson Cancer Survival Center West
    • Knoxville, Tennessee, United States, 37932
      • Recruiting
      • Thompson Oncology Group - West
    • Lenoir City, Tennessee, United States, 37772
      • Recruiting
      • Thompson Oncology Group - Lenoir City
    • Maryville, Tennessee, United States, 37804
      • Recruiting
      • Thompson Oncology Group
    • Oak Ridge, Tennessee, United States, 37830
      • Recruiting
      • Thompson Oncology Group - Oak Ridge

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: 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 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: 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)
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: 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)

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 (Estimated): February 19, 2027
• Study Completion (Estimated): February 8, 2029

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 (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: DLBCL; Lymphoma; Relapsed; Refractory; Lenalidomide; CD19; CD47; Tafasitamab; Maplirpacept
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide
• Other Study ID Numbers: C4971003; 2022-50242721-00 (Registry Identifier: CTIS)

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