A phase I study to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of KH617 for patients with advanced solid tumors (including diffuse gliomas of adulthood).

Abstract

2046 Background: Outcomes in patients (pts) with recurrent glioblastoma (rGBM) are poor, with historical median overall survival (mOS) of 7-8 months. KH617 is a sesquiterpene compound that exhibits a wide spectrum of anti-cancer properties, has low toxicity, and is capable of traversing the blood-brain barrier. It can inhibit the growth, proliferation, and migration of tumors via multiple mechanisms, mitigate the malignant phenotype of tumor cells, and facilitate the transdifferentiation of tumor cells into normal cells. This is a phase I study of KH617 in pts with advanced solid tumors (including diffuse gliomas of adulthood). Here, we report the results of the dose escalation stage. Methods: Pts with histologically confirmed advanced solid tumors (including diffuse gliomas of adulthood) that were no longer responding to standard therapies were enrolled. The Bayesian Optimal Interval (BOIN) design was used for dose escalation, having explored in 7 successive cohorts (5-60mg/kg). Results: As of Dec, 30 2025, 32 pts were enrolled across 7 dose levels, including 23 pts with rGBM, 7 with non-glioblastoma, and 1 each with adenocarcinoma and spinal cord ependymoma. The median age was 51 years, and 19 (59.4%) pts were male. No dose-limiting toxicity (DLT) or treatment-related serious adverse events (TRSAEs) were observed, and the maximum tolerated dose (MTD) was not reached. The most frequently reported (≥10%) treatment-related serious adverse events (TRAEs) were white blood cell count decreased, neutrophil count decreased, lymphocyte count decreased, abnormal ECG T wave, and sinus bradycardia. Only 1(3.13%) pt reported grade ≥3 adverse event. Efficacy signals were observed especially in the 23 rGBM pts, who were administered KH617 across 7 doses (n = 1, 1, 3, 2, 8, 7, 1 in 5, 10, 17, 25, 33, 45, 60mg/kg cohorts, respectively), the mOS was 16.07 months. At the recommended phase 2 dose (RP2D) of 33mg/kg, 8 rGBM pts were included in the efficacy evaluation, objective response rate (ORR) was 12.5%, median progression-free survival (PFS) was 1.84 months, mOS exceeded 21 months (3 died and 5 were still alive). In the pharmacokinetic (PK) study, C max no longer increased with escalating doses from 25 mg/kg to 45 mg/kg, indicating that the peak plasma concentration had already reached the maximum plateau level under the current dosing. Combined the efficacy data with the PK data, 33 mg/kg was confirmed as the RP2D. Conclusions: KH617 has shown significantly superior anti-tumor activity compared to the historical mOS in pts with rGBM, while also being well-tolerated. Clinical trial information: CTR20223286.