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.

• ClinicalTrials.gov Identifier: NCT05896163
• Recruitment Status: Recruiting
• First Posted: June 9, 2023
• Last Update Posted: April 2, 2024
• Sponsor: Pfizer
• Collaborator: Hoffmann-La Roche
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: May 10, 2023
• First Posted Date: June 9, 2023
• Last Update Posted Date: April 2, 2024
• Actual Study Start Date: August 30, 2023
• Estimated Primary Completion Date: February 23, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 30, 2023)

• Phase 1b: Number of participants with Dose limiting toxicities (DLT) [ Time Frame: 21 days following first PF-07901801 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 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 proportion of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Lugano Response Classification Criteria 2014.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 30, 2023)

• 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 PF-07901801 or 90 days after last dose of glofitamab or obinutuzumab (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). 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 [ 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) ]
  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 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 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) [ 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) ]
  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) [ 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 date of first dose of study intervention until PD, or death due to any cause, whichever occurs first (assessed up to approximately 24 months) ]
  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) [ 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) ]
  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 [ 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) ]
  Pre- and post-dose concentrations of PF-07901801
• Phase 1b and Phase 2: Serum Concentration Versus Time Summary 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. ]
  pre- and post-dose concentrations of glofitamab
• Phase 1b and Phase 2: Number of participants with Anti-Drug Antibody (ADA) against 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) ]
  To evaluate immunogenicity of PF-07901801
• Phase 1b and Phase 2: Number of participants with Anti-Drug Antibody (ADA) against 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). ]
  To evaluate immunogenicity of glofitamab
• Phase 1b and Phase 2: Number of participants with Neutralizing antibody (NAb) for 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) ]
  To evaluate immunogenicity of PF-07901801

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Open label/randomized

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Diffuse Large B-Cell Lymphoma

Intervention

• Drug: maplirpacept (PF-07901801)
  Intravenous infusion
• Drug: Glofitamab
  Intravenous infusion
• Drug: Obinutuzumab
  Intravenous infusion

Study Arms

• Experimental: Phase 1b
  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.
  Interventions:

  • Drug: maplirpacept (PF-07901801)
  • Drug: Glofitamab
  • Drug: Obinutuzumab
• Experimental: Phase 2
  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).
  Interventions:

  • Drug: maplirpacept (PF-07901801)
  • Drug: Glofitamab
  • Drug: Obinutuzumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 30, 2023): 70
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 12, 2029
• Estimated Primary Completion Date: February 23, 2027 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Pfizer CT.gov Call Center; 1-800-718-1021; ClinicalTrials.gov_Inquiries@pfizer.com

• Listed Location Countries: Japan, Taiwan, United States

Administrative Information

• NCT Number: NCT05896163
• Other Study ID Numbers: C4971006; 2022-502822-41-00 ( Registry Identifier: CTIS (EU) )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Hoffmann-La Roche

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: March 2024