Iksuda Reports 50% ORR With IKS014 After T-DXd in HER2+ Breast Cancer

Iksuda Therapeutics will present preliminary Phase 1 clinical data for IKS014 (caxmotabart entudotin), its HER2-directed antibody-drug conjugate (ADC), at the San Antonio Breast Cancer Symposium (SABCS 2026), scheduled for December 8–11 in San Antonio, Texas. The findings include a pooled efficacy analysis in patients with advanced or metastatic HER2-positive (HER2+) breast cancer previously treated with trastuzumab deruxtecan (T-DXd).

The results are notable because they indicate preliminary antitumour activity in a heavily pretreated population following exposure to another HER2-directed ADC, an area of increasing clinical interest as treatment sequencing becomes more important in HER2-positive cancers.

Phase 1 Study Design and Patient Enrollment

The open-label, multicentre Phase 1 study (NCT05872295) evaluates IKS014 in patients with HER2-expressing advanced solid tumours that are refractory to or have progressed following standard therapies. The study comprises two parts: dose escalation and dose expansion.

As of April 2026, 105 patients had been enrolled across both study parts. In Part I, 71 patients received IKS014 at doses ranging from 40 to 120 mg/m² once every three weeks. Although a maximum tolerated dose (MTD) was not identified, 105 mg/m² was selected for further evaluation based on emerging antitumour activity across tumour types and the observed safety profile.

Part II had enrolled 34 patients across five tumour-specific expansion cohorts to further evaluate safety, pharmacokinetics, pharmacodynamics and efficacy.

Safety and Tolerability

Across the 105-patient dataset, Grade 3 treatment-related adverse events (TRAEs) occurred in 16 patients (15.2%). Hypokalaemia was the most common Grade 3 TRAE, affecting seven patients (6.7%).

The most frequently reported TRAEs were hypokalaemia (36%), dry eye (34%), keratitis (34%) and dry mouth (28%), predominantly Grade 1 or 2 events.

The company also reported an absence of high-grade pneumonitis/interstitial lung disease (ILD), neutropenia, anaemia, fatigue, AST elevation and gastrointestinal toxicities. No Grade 5 events or treatment-related serious adverse events were reported.

These findings suggest a potentially differentiated tolerability profile. However, comparisons with other HER2-directed ADCs remain descriptive and do not establish comparative safety superiority.

Antitumour Activity Following Trastuzumab Deruxtecan

The pooled efficacy analysis included 10 response-evaluable patients with advanced or metastatic HER2+ breast cancer previously treated with T-DXd. Four patients had received IKS014 at doses of at least 90 mg/m² during dose escalation, while six were enrolled in the expansion cohort.

Patients were heavily pretreated, with a median of six previous treatment regimens (range: 2–12). The objective response rate (ORR) was 50% (5/10), comprising confirmed and unconfirmed partial responses.

Notably, responses were observed in patients whose best response to previous T-DXd treatment had been progressive disease. One patient maintained a response for more than 18 months, indicating the possibility of durable activity in at least a subset of patients.

Although encouraging, the response rate is based on a small subgroup and includes unconfirmed responses. Further follow-up and evaluation in a larger cohort will be necessary to establish the consistency and durability of these findings.

Clinical Development and SABCS Presentation

The expansion cohort evaluating HER2+ breast cancer following T-DXd is planned to recruit 25 patients. Recruitment will also continue across cohorts assessing HER2-low breast cancer, HER2+ gastric/gastroesophageal junction and oesophageal cancers, and HER2-mutated lung cancer.

IKS014 combines a HER2-targeting antibody with the cytotoxic payload monomethyl auristatin F (MMAF), a tubulin polymerisation inhibitor. A β-glucuronide linker enables tumour-selective enzymatic payload activation and release, with the design intended to limit exposure to healthy tissues.

The preliminary findings will be presented under the title, “A Phase 1 study of IKS014 (caxmotabart entudotin) in patients with HER2+ solid tumours, and preliminary activity in breast cancer patients previously treated with trastuzumab deruxtecan.”

The presentation is scheduled for December 9, 2026, from 7:00 to 8:30 a.m. CST (Abstract 602; Presentation PS3-1; Location 301 ABC). Iksuda stated that the dataset is evolving and that updated findings will be included in the conference presentation.

Clinical Significance

The preliminary 50% ORR in previously T-DXd-treated patients provides an early clinical signal for IKS014 in the post-T-DXd treatment setting. Responses in patients whose disease previously progressed on T-DXd are particularly relevant because they raise the possibility that an ADC using a different payload and linker design may retain activity after prior HER2-directed ADC exposure.

However, the small response-evaluable population, inclusion of unconfirmed responses and absence of comparative clinical data limit conclusions about its potential role in treatment sequencing. Updated SABCS findings and continued dose expansion will be important in determining whether this activity translates into a reproducible clinical benefit.

Reference

Iksuda to present clinical data for IKS014 in HER2+ solid tumours at SABCS, Iksuda Therapeutics, 02 November 2026

IKS014 in Advanced Solid Tumors That Express HER2, ClinicalTrials.gov ID NCT05872295