Effects of Maplirpacept (PF-07901801),Tafasitamab, and Lenalidomide in People With Relapsed or Refractory Diffuse Large B-cell Lymphoma
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| ClinicalTrials.gov Identifier: NCT05626322 |
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Recruitment Status :
Recruiting
First Posted : November 23, 2022
Last Update Posted : May 19, 2023
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Diffuse Large B-Cell Lymphoma | Drug: Maplirpacept Drug: Tafasitamab Drug: Lenalidomide | Phase 2 |
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 (Clinical Trial) |
| Estimated Enrollment : | 70 participants |
| Allocation: | Randomized |
| Intervention Model: | Sequential Assignment |
| Intervention Model Description: | Open label/randomized |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Estimated Study Start Date : | May 23, 2023 |
| Estimated Primary Completion Date : | October 20, 2025 |
| Estimated Study Completion Date : | April 23, 2026 |
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Maplirpacept
Intravenous infusion
Other Name: PF-07901801, TTI-622 Drug: Tafasitamab Intravenous infusion
Other Name: Minjuvi, Monjuvi Drug: Lenalidomide Oral (by mouth)
Other Name: Revlimid |
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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).
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Drug: Maplirpacept
Intravenous infusion
Other Name: PF-07901801, TTI-622 Drug: Tafasitamab Intravenous infusion
Other Name: Minjuvi, Monjuvi Drug: Lenalidomide Oral (by mouth)
Other Name: Revlimid |
- Phase 1b: Dose limiting toxicity (DLT) rate [ Time Frame: 28 days following first dose ]DLTs are a predefined set of adverse events that are at least possibly related to any or all of the investigational agents.
- Phase 2: Objective Response Rate (ORR) [ Time Frame: 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) ]OR defined as complete response or partial response as per Lugano Response Classification Criteria 2014
- Phase 1b and Phase 2: Frequency of adverse events (AE) [ Time Frame: 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) ]Type and severity (severity according to the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 5.0).
- Phase 1b and Phase 2: Frequency of clinical laboratory abnormalities [ Time Frame: 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) ]Type and severity (severity according to the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 5.0).
- Phase 1b: Objective Response Rate (ORR) [ Time Frame: 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) ]OR defined as complete response or partial response per Lugano Response Classification Criteria 2014
- Phase 1b and Phase 2: Duration of Response (DoR) [ Time Frame: 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) ]CR and PR defined per Lugano Response Classification Criteria 2014
- Phase 1b and Phase 2: Complete Response Rate (CRR) [ Time Frame: 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) ]CR defined per Lugano Response Classification Criteria 2014
- Phase 1b and Phase 2: Duration of Complete Response (DoCR) [ Time Frame: 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) ]CR defined per Lugano Response Classification Criteria 2014
- Phase 1b and Phase 2: Progression Free Survival (PFS) [ Time Frame: 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) ]Progression defined per Lugano Response Classification Criteria 2014
- Phase 1b and Phase 2: Pharmacokinetic parameters of PF-07901801 [ Time Frame: 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) ]Pre- and post-dose concentrations of PF-07901801
- Phase 1b and Phase 2: Pharmacokinetic parameters of tafasitamab [ Time Frame: 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) ]Pre-dose concentrations of tafasitamab
- Phase 1b and Phase 2: Pharmacokinetic parameters of of lenalidomide [ Time Frame: On the first first day of the first four 28-day cycles. ]Pre-dose concentrations of lenalidomide.
- Phase 1b and Phase 2: Incidence of Anti-Drug Antibody (ADA) against PF-07901801 [ Time Frame: 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) ]To evaluate immunogenicity of PF-07901801
- Phase 1b and Phase 2: Incidence of Anti-Drug Antibody (ADA) against tafasitamab [ Time Frame: 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) ]To evaluate immunogenicity of tafasitamab
- Phase 1b and Phase 2: Neutralizing antibody (NAb) titers for PF-07901801 [ Time Frame: 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) ]To evaluate immunogenicity of PF-07901801
- Phase 1b and Phase 2: Neutralizing antibody (NAb) titers for tafasitamab [ Time Frame: 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) ]To evaluate immunogenicity of tafasitamab
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05626322
| Contact: Pfizer CT.gov Call Center | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
| United States, Louisiana | |
| Mary Bird Perkins Cancer Center Baton Rouge | Recruiting |
| Baton Rouge, Louisiana, United States, 70809 | |
| United States, Tennessee | |
| Thompson Cancer Survival Center | Not yet recruiting |
| Knoxville, Tennessee, United States, 37916 | |
| Thompson Cancer Survival Center | Recruiting |
| Knoxville, Tennessee, United States, 37916 | |
| Thompson Cancer Survival Center West | Recruiting |
| Knoxville, Tennessee, United States, 37932 | |
| Thompson Oncology Group - West | Recruiting |
| Knoxville, Tennessee, United States, 37932 | |
| Thompson Oncology Group - Lenoir City | Recruiting |
| Lenoir City, Tennessee, United States, 37772 | |
| Thompson Oncology Group | Recruiting |
| Maryville, Tennessee, United States, 37804 | |
| Thompson Oncology Group - Oak Ridge | Recruiting |
| Oak Ridge, Tennessee, United States, 37830 | |
| Japan | |
| Japanese Foundation for Cancer Research | Not yet recruiting |
| Koto, Tokyo, Japan, 135-8550 | |
| Puerto Rico | |
| Auxilio Mutuo Cancer Center | Recruiting |
| San Juan, Puerto Rico, 00918 | |
| Study Director: | Pfizer CT.gov Call Center | Pfizer |
| Responsible Party: | Pfizer |
| ClinicalTrials.gov Identifier: | NCT05626322 |
| Other Study ID Numbers: |
C4971003 2022-50242721-00 ( Registry Identifier: CTIS ) |
| First Posted: | November 23, 2022 Key Record Dates |
| Last Update Posted: | May 19, 2023 |
| Last Verified: | May 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| 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. |
| URL: | https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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DLBCL Lymphoma Relapsed Refractory CD19 |
CD47 Maplirpacept Tafasitamab Lenalidomide |
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Lymphoma Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases |
Lymphoma, Non-Hodgkin Lenalidomide Immunologic Factors Physiological Effects of Drugs Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors Antineoplastic Agents |