Preliminary results from a phase I/II study of IMM0306, a CD47 and CD20 bispecific monoclonal antibody-trap, in patients with relapsed or refractory CD20-positive B-cell non-Hodgkin's lymphoma.

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7527 Background: IMM0306 is a fusion protein of CD20 monoclonal antibody with the CD47 binding domain of SIRPα on both heavy chains. It has a higher affinity for CD20 than for CD47, thus enabling its preferential and simultaneous binding to CD20 and CD47 on malignant B cells rather than to CD47-postive normal tissues. Here, we report the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy results of the dose escalation stage in a phase I/II study in patients (pts) with relapsed or refractory CD20-positive B-cell non-Hodgkin's lymphoma. Methods: This is a first-in-human, open-label, phase I/II study of IMM0306. The ongoing Phase I part (0.04, 0.1, 0.25, 0.5, 0.8, 1.2, 1.6, 2.0 mg/kg, IV) followed an accelerated titration and standard 3+3 design. IMM0306 was administered once per week after a 2-week single-dose period, until disease progression or intolerable toxicity. Dose-limiting toxicity (DLT) was evaluated in the first 28 days. Safety was evaluated per CTCAE 5.0, tumor assessments performed once every 8 weeks, PK and PD were also assessed. Results: As of the data cut-off date on Dec 15th, 2022, 42 pts were enrolled. 18 (43%) pts received 3 or more prior lines of therapy, all pts received prior anti-CD20 therapy. No DLTs were observed up to 2.0 mg/kg. The most frequent treatment related adverse events (TRAEs) were lymphocyte decreased (61.9%), white blood cell (WBC) decreased (61.9%), anemia (59.5%), neutrophil (ANC) decreased (40.5%), platelet (PLT) decreased (40.5%), infusion-related reactions (31.0%). Grade ≥ 3 TRAEs occurred in 30 (71.4%) pts, the most frequent grade ≥ 3 TRAEs were lymphocyte decreased (59.5%), WBC decreased (16.7%), ANC decreased (11.9%). Three treatment related SAEs were PLT decreased (grade 4), chest pain (grade 2) and diarrhea (grade 3). In 38 response evaluable pts, 2 follicular lymphoma (FL) pts achieved CR, 1 marginal zone lymphoma (MZL) pt and 2 FL pts achieved PR and 13 pts showed SD. 26 pts were treated at doses ≥ 0.8 mg/kg, among whom 11 were FL pts. Of these 11 FL pts, 4 (36%) responded including 2 CR both at 1.2 mg/kg and 2 PR at 1.2 and 1.6 mg/kg respectively. IMM0306 exhibited approximate dose-proportional increase in PK exposure from 0.5 to 2.0 mg/kg and no obvious accumulation was observed after repeated dosing. B-cell counts depleted rapidly at doses ≥ 0.8 mg/kg. Elevated cytokines levels were observed after first dosing of IMM0306, but multiple dosing did not stimulate further cytokine activation. Conclusions: IMM0306 was well-tolerated and with a robust preliminary anti-tumor activity especially in pts with R/R FL and MZL. The phase I/II study is ongoing. Clinical trial information: CTR20192612 .