Efficacy and safety of second or further line KC1036 in patients with thymoma and thymic carcinoma: A multicenter, single-arm phase II trial.

Abstract

8116 Background: Patients with advanced or recurrent thymoma or thymic carcinoma (T/TC) progressing after platinum-based chemotherapy have an unmet therapeutic need. This report assessed the clinical efficacy and safety of KC1036, a novel multi-kinase inhibitor of AXL, VEGFR2, and FLT3, in the treatment of T/TC. Methods: This open-label, multicenter, single-arm, phase II study enrolled patients with advanced or recurrent T/TC who had progressed on at least one prior line of chemotherapy. Eligible participants were required to have measurable disease according to RECIST v1.1 and an ECOG performance status of 0 or 1. KC1036 was administered orally at 60 mg QD, every 21 days as a cycle, until disease progression, death or intolerable toxicities. The primary endpoint was investigator-assessed objective response rate (ORR). Results: Between February 23, 2023 and January 4, 2024, 6 thymoma (T) and 25 thymic carcinoma (TC) patients were enrolled; all had distant metastases. Median age was 47.5 years (range, 34-71) for T and 57.0 years (37-73) for TC. Most patients had an ECOG PS of 1 (T: 100%; TC: 88.0%). While all T patients received one prior line of therapy, 48.0% of TC patients had received ≥2 prior lines. At the data cutoff of June 9, 2025, with a median follow-up of 19.3 months (95% CI, 13.4-NR), the T cohort achieved 100% SD with a median PFS of 13.6 months (95% CI, 4.1-NR). The TC cohort showed an ORR of 20.0% (n=5, PR) and a DCR of 80.0% (n=15, SD), with a median PFS of 8.2 months (95% CI: 4.1-15.1) and a median DOR of 15.3 months (95% CI: 1.5-NR). Median OS was not reached in either cohort; and the 18-month OS rates were 100% and 75.5% in the T and TC cohorts, respectively. The median duration of treatment exposure was 7.1 months. Treatment-related adverse events (TRAEs) were predominantly Grade 1 or 2. Grade 3 TRAEs occurring in ≥5% of subjects were hypertension (4 [12.9%]) and diarrhea (3 [9.7%]). No Grade 4 or 5 TRAEs were reported. TRAEs leading to dose reduction and treatment discontinuation occurred in 41.9% and 3.2% of patients, respectively. Conclusions: KC1036 demonstrated promising antitumor efficacy in patients with advanced or recurrent T/TC. Additionally, KC1036 exhibited a favorable safety profile and tolerability. These encouraging outcomes support further evaluation of KC1036 in a forthcoming phase III trial. Clinical trial information: NCT05683886 .