Early analysis of activity in esophageal cancer during phase 1 dose escalation of IKS014, a HER2-targeting antibody drug conjugate (ADC), in participants with advanced HER2+ and HER2 low solid tumors.

Abstract

355 Background: IKS014 is an ADC targeting HER2 that comprises a humanized IgG1 antibody conjugated to the monomethyl auristatin F payload, via a novel β-glucuronidase-cleavable linker. IKS014 has been evaluated by a separate sponsor in trials conducted exclusively in China. Preliminary signs of anti-tumor activity, including objective responses in various tumor types, were previously noted at doses ≥ 1.0 mg/kg (≥ 40 mg/m 2 ). Methods: IKS014-01 is a non-randomized, open-label, multicenter trial of IKS014 in participants with advanced solid tumors that express HER2 (NCT05872295). The trial is divided into two parts: Part I, a dose-escalation portion (DE) and Part II which includes 4 disease-specific Expansion Cohorts. Data from the DE portion is presented. The DE portion is intended to establish the MTD and/or a recommended dose for IKS014 monotherapy to be evaluated in Part II and to provide initial safety, efficacy, PK, PD, and immunogenicity data. Key exclusion criteria include clinically significant cardiovascular, pulmonary, or hepatic disease; or active central nervous system involvement. Participants in the DE portion must have HER2+ (IHC3+, IHC2+/ISH+) or HER2 low (IHC2+/ISH- or IHC1+) expressing solid tumors. IKS014 is infused once every 3 weeks. Participants were enrolled into cohorts of increasing dose levels using a standard 3+3 design and monitored for DLTs during Cycle 1. Results: As of July 2025, 62 patients have been treated with IKS014 across five dose levels (40, 60, 90, 120 and 105 mg/m 2 ) including 4 enrichment cohorts, during Part I DE. Among the safety population (across all dose levels and tumor indications); the most common treatment-related adverse events in descending order were dry eye, hypokalemia, keratitis, dry mouth, nausea, pneumonitis, fatigue, alopecia, decreased appetite, and aminotransferase increased. Per protocol, the MTD has not been achieved as only one dose limiting toxicity (DLT) has been observed to date. A DLT of Grade 3 Infusion Reaction was seen in 1 of 21 patients treated at the 120 mg/m 2 dose level. Encouraging anti-tumor activity was seen across all dose levels and in various tumor indications such as breast, esophageal, ovarian and gallbladder cancer and in patients with HER2+ and HER2 low tumors. Of interest, 10 patients with HER2+ esophageal cancer, who had received prior therapy (median 3, range 1-6), have been enrolled in the study. All patients had received prior HER2-targeting therapies such as trastuzumab or trastuzumab emtansine. Among these 10 patients, 5 have achieved a response and 3 demonstrated stable disease > 6 months resulting in a clinical benefit rate (CBR) of 80% with IKS014. Conclusions: These early signs of activity and the high CBR in this small subset of pretreated patients with esophageal cancer warrant further exploration. Clinical trial information: NCT05872295 .