Pfizer pulls development of Trillium-acquired anti-CD47 inhibitor maplirpacept

Pfizer has terminated a Phase I/II study evaluating maplirpacept (PF-07901801) within a treatment regimen for adults with relapsed or refractory diffuse large B-cell lymphoma not eligible for stem cell transplantation or CAR-T therapy. Specifically, the study was assessing the anti-CD47 innate immune checkpoint inhibitor maplirpacept in combination with Columvi (glofitamab), a CD20xCD3 bispecific T cell engager, following a single priming dose of Gazyva (obinutuzumab). Maplirpacept was one of two CD47-targeted molecules acquired by Pfizer via the USD 2.3 billion acquisition of Trillium Therapeutics completed in 2023.

The trial, which enrolled approximately 40 participants across sites in the United States, Australia, Israel, Japan, Taiwan, and Turkey, had a primary completion date of April 2026. As per the clinicaltrials.gov website, the study termination reflects a business decision as Pfizer looks to "pursue other programs/assets within the oncology portfolio", rather than any untoward safety signals or requests from regulatory authorities.

The study was structured as a multicenter, open-label, randomized Phase I/II program with a sequential design. The Phase Ib portion was intended to enroll approximately 20 participants across escalating dose levels of maplirpacept, administered intravenously in combination with fixed doses of glofitamab after a single obinutuzumab priming dose, with the primary objective of characterizing dose-limiting toxicities within the first 21 days of treatment. Participants received obinutuzumab at cycle zero, followed by two step-up doses of glofitamab before the full combination regimen began at cycle one. Maplirpacept was administered weekly for the first three cycles, then every three weeks; glofitamab was given on a 21-day cycle for approximately nine months, after which participants continued on maplirpacept alone.

The Phase II portion, targeting approximately 50 participants randomized across three maplirpacept dose levels, carried objective response rate as its primary endpoint, defined as complete or partial response per the Lugano 2014 classification criteria. Secondary endpoints included progression-free survival, duration of response, complete response rate, and pharmacokinetic and immunogenicity assessments for maplirpacept. Adverse event profiling, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome graded by ASTCT criteria, was built into both phases.

Maplirpacept's Development History and Program Contraction

The termination marks the effective end of Pfizer's maplirpacept clinical program. The asset, originally designated TTI-622 by Trillium Therapeutics, was acquired when Pfizer completed its purchase of Trillium. The molecule is a SIRPα fusion protein designed to block the CD47 "don't eat me" signal on tumor cells, thereby restoring macrophage-mediated phagocytosis.

The development history of the maplirpacept clinical trial program reveals a pattern of broad early exploration followed by progressive contraction. A Phase I study in advanced hematologic malignancies (NCT03530683) was terminated, as was a Phase I/II combination study with pegylated liposomal doxorubicin in platinum-resistant ovarian cancer (NCT05261490), and a Phase I/II study pairing maplirpacept with tafasitamab and lenalidomide in relapsed or refractory DLBCL (NCT05626322). Two regional Phase I studies — one in Japanese patients with hematologic malignancies (NCT05567887) and one in Chinese patients with advanced non-Hodgkin lymphoma or multiple myeloma (NCT05896774) — were completed, though neither generated publicly disclosed efficacy data. With the termination of NCT05896163, no active maplirpacept trials appear in the registry.

The breadth of the program's geographic and indication reach — spanning DLBCL, ovarian cancer, myeloma, and leukemia — suggests that Pfizer pursued multiple clinical hypotheses for the asset simultaneously. None converted into a registrational pathway. The second Trillium clinical-stage asset, TTI-621, a SIRPα-Fc fusion targeting the same checkpoint through a different molecular format, was also previously discontinued, leaving the USD 2.3 billion acquisition without a surviving clinical program.

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