SHERIDAN, WYOMING – July 1, 2025 – Pfizer has announced the termination of its Phase II trial evaluating the investigational CD47-targeting fusion protein maplirpacept in diffuse large B-cell lymphoma (DLBCL), citing persistent recruitment difficulties that prevented the study from meeting enrollment targets. The decision, which affects a program inherited through the company’s $2.26 billion acquisition of Trillium Therapeutics in 2021, underscores ongoing challenges in advancing CD47 inhibitors while highlighting Pfizer’s continued commitment to its hematologic oncology pipeline.
Recruitment Roadblocks Halt Mid-Stage Development
According to an update posted on a federal clinical trials database, Pfizer discontinued the study due to the “inability to recruit the planned number of subjects,” with only six patients enrolled since the trial’s launch in August 2023. The update emphasized, “The decision was not based on any safety and/or efficacy concerns.” In a statement to Endpoints News, a Pfizer spokesperson confirmed that “recruiting challenges” alone prompted the move to halt the trial.
The recruitment shortfall comes as a setback in the pursuit of effective CD47-targeted therapies for DLBCL, one of the most aggressive forms of non-Hodgkin lymphoma. However, Pfizer reaffirmed that it remains committed to advancing maplirpacept in other indications, including multiple myeloma.
CD47 Blockade: Mechanism and Ongoing Programs
Maplirpacept is a recombinant fusion protein designed to block CD47, a cell surface ligand often overexpressed in blood cancers that helps malignant cells evade phagocytosis by the immune system. By inhibiting CD47, maplirpacept aims to restore immune surveillance and stimulate both innate and adaptive anti-tumor responses. According to Pfizer’s website, CD47 overexpression correlates with worse clinical outcomes, making it a compelling target for novel cancer immunotherapies.
Despite the discontinuation of the Phase II DLBCL study, Pfizer continues to investigate maplirpacept in combination approaches. Notably, the pharma is running a Phase I/II trial pairing maplirpacept with Roche’s bispecific antibody Columvi in relapsed or refractory DLBCL. This combination study remains active and is currently recruiting patients, with a primary completion date set for September 2026.
CD47 Field Faces Broader Challenges
Pfizer’s difficulties mirror broader struggles within the CD47 inhibitor space. Earlier this year, ALX Oncology reported that its CD47-blocking agent evorpacept, when combined with Merck’s checkpoint inhibitor Keytruda, failed two mid-stage trials in patients with metastatic or unresectable recurrent head and neck cancer.
The most notable collapse in this class was Gilead’s magrolimab program. After partial clinical holds in early 2022 due to safety concerns, Gilead ultimately terminated its late-stage magrolimab trial in myelodysplastic syndromes in July 2023, citing futility. These setbacks have tempered industry enthusiasm for CD47-directed therapies, despite the continued recognition of the pathway’s potential.
Pfizer Maintains Commitment to Hematologic Oncology Innovation
While the end of this particular Phase II study reflects the operational challenges of clinical development in rare and aggressive cancers, Pfizer’s ongoing investment in maplirpacept demonstrates its broader strategic commitment to advancing next-generation immuno-oncology assets. The company’s continued efforts in multiple myeloma and combination regimens position it to potentially unlock new therapeutic avenues for patients facing limited treatment options.
For further details on Pfizer’s oncology research programs, visit www.pfizer.com.