Huadong Medicine Co., Ltd. (hereinafter referred to as "Huadong Medicine")  announced positive preliminary results from a Phase I study of HDM2005, an independently developed Class 1 innovative antibody–drug conjugate (ADC) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) or classical Hodgkin lymphoma (cHL). The results showed that HDM2005 demonstrated promising efficacy with a favorable safety and tolerability profile in B-NHL and cHL, which will support the clinical development moving forward.

ROR1 is a transmembrane protein overexpressed in various cancers, including lymphomas. HDM2005 is composed of a humanized IgG1 monoclonal antibody, a proteolytically cleavable linker, and the cytotoxic payload monomethyl auristatin E (MMAE). In preclinical studies, HDM2005 demonstrated potent anti-tumor activity across multiple lymphoma and solid tumor models. This first-in-human Phase I study (NCT06615193) enrolled patients with relapsed or refractory B-NHL or cHL. The primary objectives were to evaluate safety and tolerability, determine the maximum tolerated dose (MTD) and the recommended Phase Ⅱ doses (RP2Ds) and perform a preliminary evaluation of antitumor efficacy in lymphoma.

As of July 4, 2025, a total of 29 patients were enrolled (n=1, 4, 10, 11 and 3 in the 0.3, 1.0, 1.8. 2.5 and 2.75 mg/kg dose cohorts), including 17 patients with mantle cell lymphoma (MCL), 8 patients with diffuse large B-cell lymphoma (DLBCL), and 4 patients with cHL. Most patients (21, 72.4%) had received ≥3 prior lines of anti-tumor therapy. No patient permanently discontinued treatment due to treatment related adverse events (TRAEs). In the 1.8 mg/kg and 2.5 mg/kg cohorts, 38.1% of patients (8/21) experienced Grade ≥3 TRAEs, the most common (≥5%) being neutrophil count decrease (4 patients, 19.0%). No Grade ≥3 gastrointestinal adverse reactions or peripheral neuropathy were reported. Peripheral neuropathy occurred in 4 patients (13.8%), all of which were Grade 1 or 2.

In the 1.8 mg/kg and 2.5 mg/kg cohorts, the objective response rate (ORR) was 50% (6/12) in MCL patients, including 1 complete response (CR) and 5 partial responses (PR). The ORR was 100% (2/2) in cHL patients with CRs.

The preliminary results of this Phase I clinical trial show that HDM2005 was well-tolerated and demonstrated promising anti-tumor activity in patients with relapsed/refractory B-NHL or cHL. Huadong Medicine will commit to its "science-driven, patient-centered" mission, advance HDM2005 through clinical development and registration, and strive to bring more treatment options to patients.