Yuhan Corporation Presents Phase 1 Immuno-Oncology Trial and Leclaza Resistance Mechanism Results at AACR in the US

Yuhan Corporation Headquarters. Photo by Yuhan Corporation

On April 28 (local time), Yuhan Corporation presented the results of a Phase 1 clinical trial of YH32367 (ABL105) and the results of a resistance mechanism analysis from a Phase 3 study of Leclaza (Lazertinib) as first-line therapy at the American Association for Cancer Research (AACR 2025) held in Chicago, United States.

YH32367, an immuno-oncology drug jointly developed by Yuhan Corporation and ABL Bio, specifically binds to tumor cells expressing HER2 (human epidermal growth factor receptor 2) and stimulates 4-1BB, a T-cell activating receptor. Through this mechanism, which enhances the anti-cancer activity of immune cells, YH32367 is a bispecific antibody that increases tumor-specific immune activation while simultaneously inhibiting the growth of tumor cells.

This clinical trial is the first-in-human Phase 1/2 study to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of YH32367 in patients with HER2-positive locally advanced or metastatic solid tumors. The trial consists of a dose-escalation part and a dose-expansion part. The results presented this time are from the dose-escalation part conducted in Korea and Australia. Since October 2022, a total of 32 patients (14 with bile duct cancer, 9 with gastric cancer, and 9 with other solid tumors) were enrolled. The dose was escalated in eight steps from 0.3 mg/kg to 30 mg/kg and administered every three weeks.

In the clinical trial, no dose-limiting toxicity (DLT) was observed at any dose, and the maximum tolerated dose (MTD) was not reached. Treatment-related adverse events (TRAEs) were reported in 10 patients (31%), mostly presenting as fever and chills, and were predominantly mild (Grade 1 or 2). Among 31 patients with measurable lesions, 7 achieved a partial response (PR) and 10 achieved stable disease (SD), resulting in an objective response rate (ORR) of 23% and a disease control rate (DCR) of 55%.

Kim Yeolhong, Head of R&D at Yuhan Corporation, stated, "Through the clinical data presented at this AACR, we have confirmed the excellent safety profile and encouraging anti-tumor activity of YH32367." He added, "We have selected two candidate doses and are currently conducting the dose-expansion part in patients with HER2-positive bile duct cancer and various solid tumors in Korea, Australia, and the United States. We expect that YH32367 will become a treatment option for patients with bile duct cancer and other solid tumors in the future."

Meanwhile, follow-up analysis results of the LASER 301 study, which led to the approval of Leclaza as a first-line therapy for advanced EGFR (epidermal growth factor receptor) non-small cell lung cancer, were also presented. In this study, the resistance mechanisms of Leclaza were evaluated in 82 patients who underwent next-generation sequencing (NGS) both before treatment and at disease progression.

Genetic mutations in the EGFR-related pathway were observed in 16% of all patients, with the EGFR C797S mutation being the most frequent. Mutations in genes outside the EGFR pathway were identified in 43% of patients, with PIK3CA and TP53 mutations being particularly common. These genetic mutations did not show a clear correlation with the duration of treatment. In addition, clearance of circulating tumor DNA (ctDNA), known as a prognostic indicator after Leclaza treatment, was confirmed in 94% of patients, suggesting that Leclaza has a strong inhibitory effect on EGFR mutations.

Cho Byoungchul, Professor of Medical Oncology at Yonsei Cancer Center, who participated in this study, explained the significance of the announcement, stating, "Through this resistance analysis, we have gained valuable data that will help us understand the resistance mechanisms of Leclaza and develop future therapeutic strategies, and we have reconfirmed the strong inhibitory effect of Leclaza on EGFR-mutant non-small cell lung cancer."