Introduction JS203 is a bispecific CD20 x CD3 antibody, with a lower affinity for CD3 than other products in the class. The Phase I study (NCT05618327) evaluated the safety, tolerability, and preliminary efficacy of JS203 in R/R B-NHL. Here, we present updated data at the recommended Phase 2 dose (RP2D).

Methods This Phase I study consists of three parts: dose escalation, dose expansion, and indication expansion. Patients with pathologically documented CD20-positive B-NHL who received at least 1 prior line of treatment were eligible for enrollment. JS203 was administered on a weekly step-up dosing schedule over the first 28 days (Cycle 1), followed by administration of the target dose every 3 weeks until disease progression or unacceptable toxicity. To mitigate cytokine release syndrome, a single dose of rituximab (or biosimilar) was administered 3 days before the first dose of JS203 in the 2 highest dose groups. The primary endpoints were the maximum tolerated dose (MTD) and the RP2D.

Results As of July 25, 2025, 99 patients were enrolled in the study, with a median follow-up period of 4.7 months. The majority of patients had diffuse large B-cell lymphoma (DLBCL, 51.5%) or follicular lymphoma (FL, 36.4%). All patients previously received anti-CD20 treatment with a median of 3 prior therapies.

Target doses up to 30 mg were evaluated and the MTD was not reached. A regimen of step-up dosing of 0.3 mg, 1 mg, 5 mg, and 30 mg in consecutive week in the first cycle, followed by 30 mg every 3 weeks was determined to be the RP2D. Among all patients who received the RP2D (n = 61), 91.8% experienced at least 1 treatment-emergent adverse event (TEAE). The most common TEAEs (incidence ≥ 20%) were neutrophil count decreased (45.9%), lymphocyte count decreased (44.3%), white blood cell count decreased (37.7%), anemia (37.7%), alanine aminotransferase increased (29.5%), cytokine release syndrome (26.2%), and platelet count decreased (21.3%). None of the patients developed immune effector cell-associated neurotoxicity syndrome (ICANS) or tumor flare.

Among the 41 evaluable patients at the RP2D, the overall response rate was 65.8% (27/41), including 63.3% (19/30) in DLBCL, 62.5% (5/8) in FL, and 100% (3/3) in mantle cell lymphoma. The median time to response were 2.2 months, 2.3 months and 2.2 months, respectively. The median progression-free survival and duration of response have not yet been reached.

Conclusions JS203 monotherapy demonstrated promising anti-tumor activity with high response rates and early responses across different subtypes at the RP2D, and a tolerable safety profile.

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2025
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