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A Study to Learn About the Effects of Two Study Medicines (Maplirpacept [PF-07901801] And Glofitamab) When Given Together In People With Relapsed Or Refractory Diffuse Large B Cell Lymphoma.

Primary Purpose

Diffuse Large B-Cell Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
maplirpacept (PF-07901801)
Glofitamab
Obinutuzumab
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma focused on measuring DLBCL, Lymphoma, Relapsed, Refractory, CD20, CD3, CD47, Glofitamab, Obinutuzumab, Maplirpacept

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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 Key Exclusion Criteria: Prior treatment with anti-CD47 and/or prior glofitamab or anti-CD20 x CD3 containing regimen. Refractoriness to an obinutuzumab monotherapy containing regimen. Prior allogeneic stem cell transplantation or autologous stem cell transplantation within 12 weeks prior to enrolment High Grade B-Cell Lymphoma Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection.

Sites / Locations

  • Allina Health Cancer Institute - Abbott Northwestern Hospital
  • Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
  • Shizuoka Cancer CenterRecruiting
  • National Hospital Organization Kyushu Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Phase 1b

Phase 2

Arm Description

Participants will be allocated to sequential dose levels of PF-07901801, administered in combination with fixed doses of glofitamab after a dose of obinutuzumab, to select two doses of PF-07901801 for further evaluation in Phase 2. Approximately 20 participants will be enrolled.

Participants will be randomized to 1 of 2 different dose levels of PF-07901801 which will be administered in combination with fixed doses of glofitamab after a dose of obinutuzumab. Approximately 50 participants will be enrolled (25 per dose).

Outcomes

Primary Outcome Measures

Phase 1b: Number of participants with Dose limiting toxicities (DLT)
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)
OR defined as proportion of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Lugano Response Classification Criteria 2014.

Secondary Outcome Measures

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). Severity of Cytokine Release Syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) assessed according to ASTCT criteria.
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).
Phase 1b: Objective Response (OR)
OR defined as proportion of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Lugano Response Classification Criteria 2014.
Phase 1b and Phase 2: Duration of Response (DoR)
DoR defined as the time from the first documentation of OR until progressive disease (PD), or death due to any cause, whichever occurs first.
Phase 1b and Phase 2: Complete Response (CR)
CR defined per Lugano Response Classification Criteria 2014
Phase 1b and Phase 2: Duration of Complete Response (DoCR)
DoCR defined as the time from the first documentation of a CR until PD, or death due to any cause, whichever occurs first.
Phase 1b and Phase 2: Progression Free Survival (PFS)
PFS is defined as the time from the date of first dose until PD per Lugano Response Classification Criteria 2014, or death due to any cause, whichever occurs first.
Phase 1b and Phase 2: Serum Concentration Versus Time Summary of PF-07901801
Pre- and post-dose concentrations of PF-07901801
Phase 1b and Phase 2: Serum Concentration Versus Time Summary of glofitamab
pre- and post-dose concentrations of glofitamab
Phase 1b and Phase 2: Number of participants with Anti-Drug Antibody (ADA) against PF-07901801
To evaluate immunogenicity of PF-07901801
Phase 1b and Phase 2: Number of participants with Anti-Drug Antibody (ADA) against glofitamab
To evaluate immunogenicity of glofitamab
Phase 1b and Phase 2: Number of participants with Neutralizing antibody (NAb) for PF-07901801
To evaluate immunogenicity of PF-07901801

Full Information

First Posted
May 10, 2023
Last Updated
September 14, 2023
Sponsor
Pfizer
Collaborators
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT05896163
Brief Title
A Study to Learn About the Effects of Two Study Medicines (Maplirpacept [PF-07901801] And Glofitamab) When Given Together In People With Relapsed Or Refractory Diffuse Large B Cell Lymphoma.
Official Title
A PHASE 1b/2, OPEN-LABEL STUDY OF PF-07901801 IN COMBINATION WITH GLOFITAMAB AFTER A FIXED, SINGLE DOSE OF OBINUTUZUMAB IN PARTICIPANTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA NOT ELIGIBLE FOR STEM CELL TRANSPLANTATION
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 30, 2023 (Actual)
Primary Completion Date
September 3, 2026 (Anticipated)
Study Completion Date
July 1, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
Collaborators
Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to learn about the effects of two study medicines (maplirpacept [PF-07901801] and glofitamab) when given together for the treatment of diffuse large B-cell lymphoma (DLBCL) that is relapsed or is refractory. Relapsed means has returned after last treatment. Refractory means that it has not responded to last treatment. The two study medicines are given after a single dose of obinutuzumab which is the third study medicine. 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 adult participants who: Have histologically confirmed diagnosis of DLBCL Have received at least one first line of treatment for NHL. Are unable or unwilling to undergo a stem cell transplant or CAR-T cell therapy. Stem cell transplant is a procedure in which a patient receives healthy blood-forming cells to replace their own stem cells that have been destroyed by treatment. A CAR-T therapy is a type of treatment in which a patient's T cells are changed in the laboratory so they will attack cancer cells. Everyone in this study will receive all three medicines at the study site by intravenous (IV) infusion which is given directly into a vein. The two study medicines (maplirpacept [PF-07901801] and glofitamab) will be given in 21-day cycles. At Cycle 0, participants will receive a single dose of obinutuzumab pre-treatment followed by two step-up doses of glofitamab. The combination of maplirpacept (PF-07901801) with glofitamab full dose will be administered for the first time at Cycle 1 Day 1. Maplirpacept (PF-07901801) will be given weekly for the first three cycles and then every three weeks. Glofitamab will be given every 3 weeks for approximately 9 months. Thereafter participants will continue to receive maplirpacept alone. Maplirpacept (PF-07901801) will be given at different doses to different participants. Everyone taking part will receive the same fixed doses of glofitamab and obinutuzumab studied in patients with DLBCL. The study will compare the experiences of people receiving different doses of maplirpacept (PF-07901801). This will help to determine what dose is safe and effective when given with the other 2 study medicines.
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 fixed doses of glofitamab after a single dose of obinutuzumab 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 glofitamab, 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 glofitamab.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-Cell Lymphoma
Keywords
DLBCL, Lymphoma, Relapsed, Refractory, CD20, CD3, CD47, Glofitamab, Obinutuzumab, Maplirpacept

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Open label/randomized
Masking
None (Open Label)
Allocation
Randomized
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase 1b
Arm Type
Experimental
Arm Description
Participants will be allocated to sequential dose levels of PF-07901801, administered in combination with fixed doses of glofitamab after a dose of obinutuzumab, to select two doses of PF-07901801 for further evaluation in Phase 2. Approximately 20 participants will be enrolled.
Arm Title
Phase 2
Arm Type
Experimental
Arm Description
Participants will be randomized to 1 of 2 different dose levels of PF-07901801 which will be administered in combination with fixed doses of glofitamab after a dose of obinutuzumab. Approximately 50 participants will be enrolled (25 per dose).
Intervention Type
Drug
Intervention Name(s)
maplirpacept (PF-07901801)
Intervention Description
Intravenous infusion
Intervention Type
Drug
Intervention Name(s)
Glofitamab
Intervention Description
Intravenous infusion
Intervention Type
Drug
Intervention Name(s)
Obinutuzumab
Intervention Description
Intravenous infusion
Primary Outcome Measure Information:
Title
Phase 1b: Number of participants with Dose limiting toxicities (DLT)
Description
DLTs are a predefined set of adverse events that are at least possibly related to any or all of the investigational agents.
Time Frame
21 days following first PF-07901801 dose
Title
Phase 2: Objective Response (OR)
Description
OR defined as proportion of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Lugano Response Classification Criteria 2014.
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)
Secondary Outcome Measure Information:
Title
Phase 1b and Phase 2: Frequency of adverse events (AE)
Description
Type and severity (severity according to the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 5.0). Severity of Cytokine Release Syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) assessed according to ASTCT criteria.
Time Frame
Time from the date of first dose of study intervention through 28 days after last dose of PF-07901801 or 90 days after last dose of glofitamab or obinutuzumab (assessed up to approximately 24 months)
Title
Phase 1b and Phase 2: Frequency of clinical laboratory abnormalities
Description
Type and severity (severity according to the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 5.0).
Time Frame
Time from the date of first dose of study intervention through 28 days after last dose of PF-07901801 or 90 days after last dose of glofitamab or obinutuzumab (assessed up to approximately 24 months)
Title
Phase 1b: Objective Response (OR)
Description
OR defined as proportion of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Lugano Response Classification Criteria 2014.
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)
Title
Phase 1b and Phase 2: Duration of Response (DoR)
Description
DoR defined as the time from the first documentation of OR until progressive disease (PD), or death due to any cause, whichever occurs first.
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)
Title
Phase 1b and Phase 2: Complete Response (CR)
Description
CR defined per Lugano Response Classification Criteria 2014
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)
Title
Phase 1b and Phase 2: Duration of Complete Response (DoCR)
Description
DoCR defined as the time from the first documentation of a CR until PD, or death due to any cause, whichever occurs first.
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)
Title
Phase 1b and Phase 2: Progression Free Survival (PFS)
Description
PFS is defined as the time from the date of first dose until PD per Lugano Response Classification Criteria 2014, or death due to any cause, whichever occurs first.
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)
Title
Phase 1b and Phase 2: Serum Concentration Versus Time Summary of PF-07901801
Description
Pre- and post-dose concentrations of PF-07901801
Time Frame
Pre and post-infusion on Day 1 of Cycle 1 and 2 (each cycle is 21 days), Pre-infusion on Day 8 of Cycle 1, Pre-infusion on Day 1 of Cycles 3, 4, 5, 7, 10, 13 and every 6 cycle thereafter until end of treatment (approximately 24 months)
Title
Phase 1b and Phase 2: Serum Concentration Versus Time Summary of glofitamab
Description
pre- and post-dose concentrations of glofitamab
Time Frame
Pre-infusion on Days 8 and 15 of Cycle 0 (cycle duration is 21 days), Pre-infusion, post-Infusion on Day 1 of Cycle 1 and 2, Pre-infusion on Day 1 of Cycle 3, 4, 7, 10 and 12.
Title
Phase 1b and Phase 2: Number of participants with Anti-Drug Antibody (ADA) against PF-07901801
Description
To evaluate immunogenicity of PF-07901801
Time Frame
On the first day of every 21-day cycle through 5 cycles, then every third cycle from cycle 7 through cycle 13 and then every sixth cycle thereafter until end of PF-07901801 treatment (assessed up to approximately 24 months)
Title
Phase 1b and Phase 2: Number of participants with Anti-Drug Antibody (ADA) against glofitamab
Description
To evaluate immunogenicity of glofitamab
Time Frame
On the 8th day of cycle 0 (cycle duration is 21 days), then the first day of every 21-day cycle through cycle 4, then the first day of cycle 7, 10 and 12 (last assessment).
Title
Phase 1b and Phase 2: Number of participants with Neutralizing antibody (NAb) for PF-07901801
Description
To evaluate immunogenicity of PF-07901801
Time Frame
On the first day of every 21-day cycle through 5 cycles, then every third cycle from cycle 7 through cycle 13 and then every sixth cycle thereafter until end of PF-07901801 treatment (assessed up to approximately 24 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 Key Exclusion Criteria: Prior treatment with anti-CD47 and/or prior glofitamab or anti-CD20 x CD3 containing regimen. Refractoriness to an obinutuzumab monotherapy containing regimen. Prior allogeneic stem cell transplantation or autologous stem cell transplantation within 12 weeks prior to enrolment High Grade B-Cell Lymphoma Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pfizer CT.gov Call Center
Phone
1-800-718-1021
Email
ClinicalTrials.gov_Inquiries@pfizer.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Allina Health Cancer Institute - Abbott Northwestern Hospital
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
466-8650
Country
Japan
Individual Site Status
Not yet recruiting
Facility Name
Shizuoka Cancer Center
City
Nagaizumi-cho,Sunto-gun
State/Province
Shizuoka
ZIP/Postal Code
411-8777
Country
Japan
Individual Site Status
Recruiting
Facility Name
National Hospital Organization Kyushu Cancer Center
City
Fukuoka
ZIP/Postal Code
811-1395
Country
Japan
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=C4971006
Description
To obtain contact information for a study center near you, click here.

Learn more about this trial

A Study to Learn About the Effects of Two Study Medicines (Maplirpacept [PF-07901801] And Glofitamab) When Given Together In People With Relapsed Or Refractory Diffuse Large B Cell Lymphoma.

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