JMT601, a bispecific left-right asymmetrical fusion protein that targets CD47 and CD20, is being investigated for the management of relapsed or refractory CD20-positive B-cell non-Hodgkin lymphoma (NHL). Preliminary efficacy and safety data from the first-in-human trial of this agent are available which the trial authors conclude show favorable anti-tumor effects and acceptable safety. They presented these data at the American Association for Cancer Research (AACR) Annual Meeting 2025 in Chicago, Illinois.
In remarks forwarded to Blood Cancers Today, Paolo Strati, MD, an associate professor and researcher in the Department of Lymphoma and Myeloma at the University of Texas MD Anderson Cancer Center, Houston, commented on the presented trial and JMT601.
“While bispecific antibodies engaging T cells are FDA approved for indolent and aggressive B-cell lymphoma, and those engaging NK cells show promising activity in HL, bispecific antibodies engaging macrophages are still at very early phase of development. The clinical development of agents targeting CD47 has been limited by hematological toxicity, underscoring the safety of this drug class,” Dr. Strati explained.
The trial enrolled 36 patients aged 18 to 70 years with histologically confirmed disease who had undergone at least two prior lines of therapy. The median age of the cohort was 59 years and 23 patients were male. 75% of the total cohort had received three or more prior lines of therapy and 75% of the total cohort had disease refractory to rituximab-based combination therapy. 25 patients specifically had diffuse large B-cell lymphoma (DLBCL).
Dr. Strati pointed out about the trial’s total enrolled cohort that “it is unclear how many were chemo-refractory and how many had previously received CAR T-cell therapy or standard bispecifics.”
In this two-part trial, 30 patients participated in a 3 plus 3 dose-escalation of JMT601 where they received weekly intravenous administration of the agent at eight dose levels until disease progression, intolerable toxicity, or consent was withdrawn. This was followed by the dose-expansion phase in which the recommended dose was administered to six patients with select tumor types. There was one instance of dose-limiting toxicity as a grade 4 thrombocytopenia which occurred at a dose of 12 mg/kg, and the maximum tolerated dose was not reached.
For the 32 patients in whom efficacy was evaluable, the calculated objective response rate (ORR) was 25%, and the disease control rate (DCR) was 50%. Among patients with DLBCL, the calculated OOR was 28% and DCR was 52%.
“Response rates were low (25%), but it is not clear how many of these were CR, and duration of response data are not reported,” Dr. Strati wrote in response to these efficacy results from the trial.
Safety was evaluated in 36 patients and 86.1% experienced a treatment-related adverse event (TRAE) of any grade. 44.4% of patients experienced a TRAE of grade 3 or worse severity; the most common types were neutropenia which occurred in 19.4%, thrombocytopenia in 13.9%, leukopenia in 11.1%, lymphocytopenia in 8.3%, hypertriglyceridemia in 5.6%, anemia in 5.6%, and infectious pneumonia in 5.6%.
Serious adverse events (SAEs) occurred in 25% of the patients. There were three TRSAEs, specifically two instances of thrombocytopenia and one of infectious pneumonia. There was one patient mortality due to disease progression deemed unrelated to the study agent.
Dr. Strati assessed that “[w]hile severe anemia was not reported frequently, 10-20% of patients experienced severe neutropenia or thrombocytopenia, whose mechanisms remains to be clarified.”
Following his review of the presented trial and its findings, Dr. Strati concluded regarding JMT 601 that “[w]hile initial activity is encouraging, macrophage biology yet remains to be unveiled for better harnessing for the treatment of lymphoma.”
Reference
AACR Annual Meeting 2025. Section #49. https://www.abstractsonline.com/pp8/#!/20273/presentation/10436
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