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

Sponsor

Pfizer (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05626322

Collaborator

MorphoSys AG (Industry), Incyte Corporation (Industry)

Enrollment

Location

Arms

34.4

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to learn about the effects of three study medicines (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 B 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 a stem cell transplant. Stem cell transplant is when doctors put healthy blood cells back into your body.

Everyone in this study will receive all three medicines. Participants will receive PF-07901801 and tafasitamab at the study clinic by intravenous (IV) infusion (given directly into a vein). Study interventions will be administered in 28-day cycles. PF-0791801 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 by mouth at home every day for Days 1 to 21 of each 28-day cycle for the first 12 cycles.

Participants can continue to take PF-07901801 and tafasitamab until their lymphoma is no longer responding. Lenalidomide is discontinued after 12 cycles.

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 dose when combined with the other 2 study medicines.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B-Cell Lymphoma	Drug: PF-07901801 Drug: Tafasitamab Drug: Lenalidomide	Phase 2

Detailed Description

This is a multicenter, open-label, Phase 1b/2 study to evaluate the safety, tolerability and potential clinical benefits of 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 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 PF-07901801 to be administered in combination with tafasitamab and lenalidomide.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

Open label/randomizedOpen 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

Anticipated Study Start Date :

Jan 18, 2023

Anticipated Primary Completion Date :

Nov 29, 2025

Anticipated Study Completion Date :

Nov 29, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1b Participants will be allocated to sequential dose levels of 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: PF-07901801 Intravenous infusion Drug: Tafasitamab Intravenous infusion Drug: Lenalidomide Oral (by mouth)
Experimental: Phase 2 Participants will be randomized to 1 of 2 different dose levels of 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: PF-07901801 Intravenous infusion Drug: Tafasitamab Intravenous infusion Drug: Lenalidomide Oral (by mouth)

Arm

Intervention/Treatment

Experimental: Phase 1b

Participants will be allocated to sequential dose levels of 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: PF-07901801

Intravenous infusion

Drug: Tafasitamab

Intravenous infusion

Drug: Lenalidomide

Oral (by mouth)

Experimental: Phase 2

Participants will be randomized to 1 of 2 different dose levels of 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: PF-07901801

Intravenous infusion

Drug: Tafasitamab

Intravenous infusion

Drug: Lenalidomide

Oral (by mouth)

Outcome Measures

Primary Outcome Measures

Phase 1b: Dose limiting toxicity (DLT) rate [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 (OR) [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

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 abnormalities [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 (OR) [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 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 (CR) [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 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 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 [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 [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 [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 [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 [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 [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 [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.