Pfizer registers new P1/2 trial of maplirpacept + glofitamab in 2L+ r/r DLBCL

On June 9^th, 2023, Pfizer registered a new, multicenter, open-label P1/2 trial (PCD: Jun 2026) assessing the safety, tolerability, and clinical benefits of maplirpacept (TTI-622; SIRPα-Fc IgG4) + glofitamab (COLUMVI; CD20 x CD3 bsAb) + obinutuzumab (GAZYVA; CD20 mAb) in 2L+ r/r DLBCL. 

Key Details and Implications:

• The newly posted trial is in line with Pfizer previously stated plan that maplirpacept (TTI-622) could be a “potential backbone combinatorial agent for heme malignancies”
  • The company has previoulsy highlighted their focus on prioritizing combinations with “expected SOC agents” (PFE EC Q1 2022)
  • Other ongoing trial of interest are: P1/2 trial (PCD: Nov 2025) evaluating maplirpacept + tafasitamab (MONJUVI; CD19 mAb) + lenalidomide (REVLIMID; IMiD) in r/r DLBCL ,  a P1b trial (PCD: Aug 2025) of maplirpacept +  elranatamab (BCMA x CD3 bsAb) in r/r MM, and a  P1China-only trial (PCD: Aug 2024) assessing the safety of maplirpacept (TTI-622; SIRPα-Fc IgG4) monotherapy in r/r NHL and MM patients
• Glofitamab is expected to be the second bsAb to enter the r/r DLBCL market with US approval expected in Q3 2023 (PDUFA action date Jul 1^st, 2023) and EU approval anticipated in 2023 (CHMP recommended conditional approval in Apr 2023) 
  • Recently presented data from extended follow-up of the pivotal P2 study of glofitamab  + obinutuzumab in r/r LBCL showed continued durable responses, with an estimated 70% of patients with a CR remaining in remission at 18mo, and a manageable safety profile (ASCO, #7550)
  • It is expected to face signficant in-class competition in the crowded CD20 x CD3 bispecific space as epcoritamab (EPKINLY; CD20 x CD3 DuoBody) was recently approved by the FDA in 3L+ r/r DLBCL and Regeneron’s odronextamab (CD20 x CD3 bsAb) BLA submissionis anticipated in H2 2023 for treatment of r/r DLBCL
  • Bispecifics are expected to become the standard of care in the r/r DLBCL treatment algorithm, as an off-the-shelf treatment option for patients ineligible for SCT and unable to receive and/or refractory CAR-T; combinations with novel agents of varying MoAs have been explored to potentially boost efficacy and improve outcomes 
• ​​​​​​​As the priortized asset of Pfizer's long term heme pipeline strategy, maplirpacept is expected to be a key in-class competitor to magrolimab as its development ramps up, however, its current development overall still lags behind that of magrolimab and is likley not a near term threat
  • Data from these early bispecific studies can also serve as POC for novel future magrolimab combinations as well
  • Maplirpacept also has the advantage of having access to Pfizer's current heme / oncology  portfolio to explore possible combinations across multiple indications