KC1036, a novel oral multi-kinase inhibitor, in patients with previously treated advanced esophageal squamous cell carcinoma (ESCC): Results from a multicenter, single-arm phase II trial

e16011 Background: Therapeutic options for patients with previously treated advanced esophageal squamous cell carcinoma (ESCC) are limited. KC1036, a novel oral multi-kinase inhibitor of AXL, VEGFR2 and FLT3, has shown promising antitumor activity in preclinical and phase I studies. Here we report the preliminary outcomes from a phase II study, including the safety of KC1036 in patients with advanced gastrointestinal cancers, and the efficacy of KC1036 as second-line or later treatment in patients with advanced ESCC. Methods: In this multicenter, open label, single-arm phase II study, patients with advanced gastrointestinal cancers refractory to standard treatment were enrolled. For patients with advanced ESCC, those who had received standard first-line PD-1 blockade plus chemotherapy were eligible. KC1036 was administered orally at 60 mg QD, every 21 days as a cycle, until disease progression, death or intolerable toxicities. Primary endpoint was objective response rate (ORR) assessed by investigators per RECIST 1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), and safety. Results: Between June 8, 2022 and December 30, 2022, 58 patients were enrolled and received at least 1 dose of KC1036. The most common tumor type was ESCC (55.2%%, 32/58), followed by gastric cancer (13.8%, 8/58) and colorectal cancer (13.8%, 8/58). The median age was 63.5 (range 55.0-67.0) years. 29 patients (50.0%) had received prior treatment with PD-1 inhibitors and 46 patients (79.3%) had received platinum-containing chemotherapy. Lung metastasis and liver metastasis were observed at baseline in 39.7% (23/58) and 48.3% (28/58) of the patients, respectively. As of the data cut-off date (December 30, 2022), treatment-related adverse events (TRAEs) of any grade occurred in 50 (86.2%, 50/58) patients. 12 patients (20.7%, 12/58) reported grade 3 TRAEs, and the most common grade 3 TRAE was hypertension (5.2%, 3/58). Grade 4-5 TRAEs were reported in 2 patients, including one case of grade 4 esophagomediastinal fistula, and one case of death from unknown cause. 24 out of the 32 patients with advanced ESCC had at least one tumor response evaluation at data cut-off. Among them, 7 had partial response (PR), 13 had stable disease (SD), and 4 had progressive disease (PD) as best response. The ORR for ESCC patients was 29.2% (95% CI: 12.6%, 51.1%), and the DCR was 83.3% (95% CI: 62.6%, 95.3%). The median PFS was 4.2 months (95% CI, 2.20, 5.75), while the median DoR had not been reached. At data cut-off, 11 patients with ESCC were still receiving KC1036 treatment. Conclusions: KC1036 showed a manageable safety profile and promising anti-tumor activity in patients with previously treated advanced ESCC. This study is ongoing with further investigation of KC1036 in ESCC patients. Clinical trial information: NCT05260385 .