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Ref Type Abstract
PMID
Authors Jianchun Duan, Jie Wang, Jie He, Jia Zhong, Rui Wan, Jin Gu, Xiaodong WANG, Liping Ma, Qian Chu, Ping Peng, Ying Cheng, Liang Zhang, Kejing Tang, Yujuan Zhou, Yingrui Shi, Ruofan Huang, Xiao-Jie Wu, Ying Yuan, Shuhua Han, and Jianxing He
Title First-in-human phase I/II study of BYS10 in patients (pts) with locally advanced or metastatic RET-altered solid tumors: Preliminary dose escalation results
Journal Vol Issue Date Pages Journal Short Title
Journal of Clinical Oncology 43 16_Suppl May 28, 2025
URL https://ascopubs.org/doi/abs/10.1200/JCO.2025.43.16_suppl.8601
Abstract Text Background: RET alterations occur in non-small cell lung cancer (NSCLC, 2%), thyroid cancer (TC, 10%–20%) and a range of tumor types (<1%). RET inhibitors substantially improved the clinical outcomes of pts with RET-altered solid tumors. BYS10 is a highly potent and RET-specific inhibitor that overcomes RET V804 and G810 mutations, and exhibits high selectivity for RET over KDR. This study is to evaluate safety, tolerability, pharmacokinetics (PK) and efficacy of BYS10 in Chinese pts with RET-altered solid tumors. Methods: In phase Ⅰ, following an accelerated titration and BOIN design, eligible pts were treated with BYS10 at 25 to 600 mg daily dose. Primary endpoints included safety, tolerability, MTD and DLTs. Secondary endpoints included PK and preliminary antitumor activity. Results: As of 10 July, 2024, a total of 51 pts were enrolled in dose escalation cohorts at 25/50 mg QD (n = 1/1) and 50/100/200/250/300 mg BID (n = 3/12/12/9/13). The MTD was not reached. Treatment related adverse events (TRAEs) occurred in all subjects, the most common TRAE were elevated AST (64.7%), elevated ALT (58.8%), elevated TBIL (45.1%), decreased WBCs (43.1%), decreased NEUT (33.3%), hyperuricaemia (31.4%), hypertension (29.4%), hypoalbuminemia (25.5%), Elevated SCr (23.5%) and headaches (23.5%). Grade 3 to 4 TRAEs >5% included elevated AST (25.5%), elevated ALT (13.7%) and hypertension (9.8%) reported at 100 to 300 mg BID doses. Serious adverse events were recorded in 7 pts. Exposure of BYS10 increased in a dose-dependent manner from 25 to 600 mg. In 40 evaluable pts, the confirmed overall response rate (ORR) and disease control rate (DCR) by independent review committee per RECIST v1.1 were 62.5% and 85%, In pts with RET-fusion NSCLC (n=30), RET-fusion thyroid cancer (TC, n=6) and RET-mutant medullary thyroid cancer (MTC, n=4), the ORR/DCR were 60%/80%, 83.3%/100% and 50%/100%, respectively. Intracranial antitumor activity was observed by investigators in 4 pts with at least 1 measurable intracranial lesion (one intracranial complete response). The ORR/DCR by IRC in 200 mg and 300 mg BID cohorts were 66.7%/100% and 75%/91.7%, respectively. Conclusions: BYS10 was well tolerated and showed dose-dependent exposure. Preliminary antitumor activity was observed in pts with RET-altered NSCLC, TC and MTC. The study is still ongoing. Clinical trial information: ChiCTR2400085264.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET fusion lung non-small cell carcinoma predicted - sensitive BYS10 Phase Ib/II Actionable In a Phase I/II trial, treatment with BYS10 resulted in an objective response rate (ORR) of 62.5% and disease control rate (DCR) of 85% in advanced solid tumors (n=40), with an ORR of 60% and DCR of 80% in patients with non-small cell lung cancer harboring a RET fusion (n=30) (J Clin Oncol 2025 43: 16_suppl, 8601). detail...
RET fusion thyroid cancer predicted - sensitive BYS10 Case Reports/Case Series Actionable In a Phase I/II trial, treatment with BYS10 resulted in an objective response rate (ORR) of 62.5% and disease control rate (DCR) of 85% in advanced solid tumors (n=40), with an ORR of 83.3% and DCR of 100% in patients with thyroid cancer harboring a RET fusion (n=6) (J Clin Oncol 2025 43: 16_suppl, 8601). detail...
RET mutant medullary thyroid carcinoma predicted - sensitive BYS10 Case Reports/Case Series Actionable In a Phase I/II trial, treatment with BYS10 resulted in an objective response rate (ORR) of 62.5% and disease control rate (DCR) of 85% in advanced solid tumors (n=40), with an ORR of 50% and DCR of 100% in patients with medullary thyroid cancer harboring a RET mutation (n=4) (J Clin Oncol 2025 43: 16_suppl, 8601). detail...