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

Registration Number
NCT05626322
Lead Sponsor
Pfizer
Brief Summary

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)
...

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 a...

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
70
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

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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Phase 1bMaplirpaceptParticipants 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.
Phase 1bTafasitamabParticipants 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.
Phase 1bLenalidomideParticipants 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.
Phase 2TafasitamabParticipants 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).
Phase 2MaplirpaceptParticipants 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).
Phase 2LenalidomideParticipants 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).
Primary Outcome Measures
NameTimeMethod
Phase 1b: Dose limiting toxicity (DLT) rate28 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 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

Secondary Outcome Measures
NameTimeMethod
Phase 1b and Phase 2: Frequency of adverse events (AE)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 abnormalitiesTime 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: Neutralizing antibody (NAb) titers for PF-07901801On 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: Objective Response Rate (ORR)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: Complete Response Rate (CRR)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: Progression Free Survival (PFS)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: Duration of Response (DoR)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: Pharmacokinetic parameters of tafasitamabOn 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: Duration of Complete Response (DoCR)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: Pharmacokinetic parameters of PF-07901801On 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 of lenalidomideOn 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-07901801On 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 tafasitamabOn 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 tafasitamabOn 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

Trial Locations

Locations (21)

LSU Health Baton Rouge North Clinic

🇺🇸

Baton Rouge, Louisiana, United States

Mary Bird Perkins Cancer Center

🇺🇸

Baton Rouge, Louisiana, United States

Thompson Cancer Survival Center

🇺🇸

Knoxville, Tennessee, United States

Thompson Cancer Survival Center West

🇺🇸

Knoxville, Tennessee, United States

Thompson Oncology Group - West

🇺🇸

Knoxville, Tennessee, United States

Winship Cancer Institute

🇺🇸

Atlanta, Georgia, United States

Our Lady of the Lake Physician Group-Medical Oncology

🇺🇸

Baton Rouge, Louisiana, United States

Our Lady of the Lake RMC

🇺🇸

Baton Rouge, Louisiana, United States

Thompson Oncology Group - Oak Ridge

🇺🇸

Oak Ridge, Tennessee, United States

Lifespan Cancer Institute

🇺🇸

Providence, Rhode Island, United States

Thompson Oncology Group - Lenoir City

🇺🇸

Lenoir City, Tennessee, United States

Japanese Foundation for Cancer Research

🇯🇵

Koto, Tokyo, Japan

The Cancer Institute Hospital of JFCR

🇯🇵

Koto, Tokyo, Japan

Kyushu University Hospital

🇯🇵

Fukuoka, Japan

Yamagata University Hospital

🇯🇵

Yamagata, Japan

Dong-A University Hospital

🇰🇷

Busan, Pusan-kwangyǒkshi, Korea, Republic of

Seoul National University Hospital

🇰🇷

Seoul, Seoul-teukbyeolsi [seoul], Korea, Republic of

Auxilio Mutuo Cancer Center

🇵🇷

San Juan, Puerto Rico

Thompson Oncology Group

🇺🇸

Maryville, Tennessee, United States

The Miriam Hospital

🇺🇸

Providence, Rhode Island, United States

University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

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