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.
Purpose
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 two first lines 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.
Condition
- Diffuse Large B-Cell Lymphoma
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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 two prior lines of systemic therapy (for phase 2, at least 2 and no more than 4 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
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.
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- Open label/randomized
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
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. |
|
|
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). |
|
|
Experimental PK Bridging Sub-Study |
Participants will be allocated to 2 dose levels of PF-07901801 manufactured with process 3, administered in combination with fixed doses of glofitamab after a dose of obinutuzumab, to evaluate the pharmacokinetic of PF-07901801 using Process 3 material and determine a dose comparable to the recommended PF-07901801 dose for phase 3 determined in Phase 2. Approximately 20 participants will be enrolled. |
|
Recruiting Locations
Fairway, Kansas 66205
Fairway, Kansas 66205
Kansas City, Kansas 66160
Kansas City, Kansas 66160
More Details
- Status
- Recruiting
- Sponsor
- Pfizer
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 and Pharmacokinetics sub-study, participants must have previously received at least 2 prior systemic treatment regimen. For Phase 2, participants must have received at least 2 but no more than 4 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. Additionally, a sub-study will evaluate the Pharmacokinetics (PK) characteristics of maplirpacept manufactured with Process 3, a new and optimized process.