[Edaily Reporter NA EUN-KYUNG ] Yuhan(000100)plans to obtain preliminary results from the Phase 1/2 clinical trial of its next-generation lung cancer treatment candidate, YH42946, by the end of this year and enter the dose-escalation phase in early 2027.

Yuhan Corporation announced on the 14th that it presented a poster at the 2026 World Conference on Lung Cancer (WCLC) held at COEX in Seoul, detailing the design, current progress, and future development plans for the Phase 1/2 “First-in-Human” clinical trial of the oral HER2-targeted therapy YH42946.

YH42946 is an oral small-molecule tyrosine kinase inhibitor (TKI) that targets human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) exon 20 insertion mutations. It is being developed to treat cancers with not only HER2 mutations but also HER2 amplification or overexpression and EGFR exon 20 insertion mutations.

This candidate compound was originally developed by J-Inz Bio, a South Korean biotech venture specializing in anticancer drug development, under the name JIN-A04. In May 2023, Yuhan Corporation signed a technology licensing agreement with J-Inz Bio worth a total of $325 million to secure the rights to develop and commercialize YH42946. The agreement included an upfront payment of $1.9 million and milestone payments tied to development, approval, and sales.

Yuhan Corporation is developing YH42946 as one of its follow-on lung cancer pipeline candidates following Lecraz. Notably, the drug is designed to target both EGFR exon 20 insertion mutations and HER2 abnormalities—tumors that are relatively resistant to existing EGFR-targeted therapies.

In preclinical studies, antitumor activity was observed in tumor models harboring HER2 mutations, amplification, and overexpression, as well as EGFR exon 20 insertion mutations. A dose-dependent antitumor effect was also observed in an intracranial HER2 tumor model. These research findings were generated in collaboration with researchers from Yonsei University and others and were published last July in the international journal *npj Precision Oncology*.

Currently, Phase 1 and 2 clinical trials are underway in adult patients with locally advanced or metastatic solid tumors accompanied by HER2 mutations, amplification, or overexpression, or EGFR exon 20 insertion mutations. These multicenter, open-label trials are evaluating safety, tolerability, pharmacokinetics (PK), and antitumor effects.

In Part 1, the dose-escalation phase, doses are being incrementally increased from 5 mg to a maximum of 240 mg to evaluate safety and efficacy. The study initially began with once-daily (QD) dosing, but a twice-daily (BID) dosing cohort was added based on the results of pharmacokinetic modeling and simulation. For certain dose levels, the company is using a “backfill” approach—enrolling additional patients—to strengthen safety, pharmacokinetic, and efficacy data.

Yuhan Corporation plans to derive initial results from Part 1—including safety, tolerability, pharmacokinetics, and preliminary antitumor effects—by the end of this year. Based on these findings, the company plans to select two doses and proceed to Part 2 in early 2027.

In Part 2, patients will be randomly assigned 1:1 to the two selected doses for comparison, after which the recommended dose (RD) will be determined. Subsequently, the company plans to expand the patient population to include other solid tumors with HER2 abnormalities.

The primary endpoints of the clinical trial are safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs). Secondary endpoints include the pharmacokinetics of YH42946 and its major metabolite M33, as well as the objective response rate (ORR), duration of response (DoR), disease control rate (DCR), and progression-free survival (PFS) assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Kim Yeol-hong, Executive Vice President of Research and Development (R&D) at Yuhan Corporation, stated, “YH42946 has the potential to become a new treatment option for patients with solid tumors harboring HER2 abnormalities and EGFR exon 20 insertion mutations, as it can be administered orally and is expected to be effective even against brain metastases,” and “We will evaluate its safety and antitumor efficacy through Phase 1 and 2 clinical trials and proceed with establishing the recommended dosage and subsequent development,” he said.