China-based Harbour Biomed (HKG: 2142) is set to release early clinical data for its CTLA-4 antibody in combination with Junshi Biosciences’ (HKG: 1877, SHA: 688180) programmed death-1 (PD-1) inhibitor toripalimab as a treatment for neuroendocrine neoplasms (NENs). The findings will be presented via a poster at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2023.
Phase Ib Study Results and Clinical Response
According to the press release, the open-label Phase Ib study was designed to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the combination treatment in patients with NEN and other solid tumor types. A total of 21 patients with pretreated, advanced, high-grade NENs received porustobart at one of two dose levels (0.3 mg/kg and 0.45 mg/kg) alongside toripalimab 240 mg every three weeks. The overall response rate (ORR) was reported at 38.9%, with a disease control rate (DCR) of 61.1%. The three-month duration of response (DOR) rate was 80%, although the median DOR was not reached. Notably, patients with neuroendocrine carcinoma (NEC) showed slightly better outcomes, with an ORR of 38.5% and a DCR of 69.2%.
Safety Profile and Treatment-Related Adverse Events
While the combination therapy demonstrated promising efficacy, treatment-related adverse events (TRAEs) were reported in 100% of participants. Grade 3 or higher TRAEs were observed in 33.3% (7 out of 21) of patients. The most common TRAEs included abnormal hepatic function, hyperthyroidism, rash, leukopenia, anemia, pyrexia, decreased neutrophil count, hypothyroidism, and thrombocytopenia.
Innovative Approach to Treating NENs
Harbour Biomed views the early data as highly promising, given the robust clinical response in challenging-to-treat high-grade NENs, which have limited alternative treatment options. The lead product, porustobart, is a fully human anti-CTLA-4 monoclonal heavy chain-only antibody (HCAb) developed on the Harbour Mice platform, designed to enhance efficacy and reduce toxicity compared to earlier-generation CTLA-4 antibodies.-Fineline Info & Tech
