Clinical trial NCT05896163: 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
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Diffuse Large B-Cell Lymphoma
Keywords: DLBCL
Lymphoma
Relapsed
Refractory
CD20
CD3
CD47
Glofitamab
Obinutuzumab
Maplirpacept
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Hoffmann-La Roche
First posted: 2023-06-09
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Open label/randomized
Primary purpose: TREATMENT

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 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.

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 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 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.

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 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

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.

Primary outcomes:
measure: Phase 1b: Number of participants with Dose limiting toxicities (DLT)
timeFrame: 21 days following first PF-07901801 dose
measure: Phase 2: Objective Response (OR)
timeFrame: 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 outcomes:
measure: Phase 1b and Phase 2: Frequency of adverse events (AE)
timeFrame: 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)
measure: Phase 1b and Phase 2: Frequency of clinical laboratory abnormalities
timeFrame: 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)
measure: Phase 1b: Objective Response (OR)
timeFrame: 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)
measure: Phase 1b and Phase 2: Duration of Response (DoR)
timeFrame: 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)
measure: Phase 1b and Phase 2: Complete Response (CR)
timeFrame: 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)
measure: Phase 1b and Phase 2: Duration of Complete Response (DoCR)
timeFrame: 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)
measure: Phase 1b and Phase 2: Progression Free Survival (PFS)
timeFrame: 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)
measure: Phase 1b and Phase 2: Serum Concentration Versus Time Summary of PF-07901801
timeFrame: 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)
measure: Phase 1b and Phase 2: Number of participants with Anti-Drug Antibody (ADA) against PF-07901801
timeFrame: 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)
measure: Phase 1b and Phase 2: Number of participants with Neutralizing antibody (NAb) for PF-07901801
timeFrame: 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)
Other outcomes:
Locations:
city: Fairway
country: United States
facility: The University of Kansas Cancer Center ,Investigational Drug Services
state: Kansas
city: Fairway
country: United States
facility: The University of Kansas Clinical Research Center
state: Kansas
city: Kansas City
country: United States
facility: The University of Kansas Hospital
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Hospital Cambridge North Tower A
state: Kansas
city: Minneapolis
country: United States
facility: Allina Health Cancer Institute - Abbott Northwestern Hospital
state: Minnesota
city: Saint Louis
country: United States
facility: Siteman Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital Parkview Tower
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Melbourne
country: Australia
facility: Epworth Freemasons
state: Victoria
city: Richmond
country: Australia
facility: Slade Pharmacy
state: Victoria
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
state: Hamerkaz
city: Haifa
country: Israel
facility: Rambam Health Care Campus
state: Hatsafon
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
state: Tell Abīb
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
state: Yerushalayim
city: Nagoya
country: Japan
facility: Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
state: Aichi
city: Nagaizumi-cho
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: