Iksuda reports a 53% response rate for CD19-directed ADC IKS03 in Phase 1 B-cell lymphoma study, including responses in previously CAR-T-treated patients.
Written By: Charvi Kalal, PharmD
Reviewed By: Pharmacally Editorial Team
Iksuda Therapeutics reported preliminary clinical results on November 5, 2026, from the dose-escalation portion of its Phase 1 study evaluating IKS03, an investigational CD19-directed antibody-drug conjugate (ADC), in patients with advanced B-cell non-Hodgkin lymphoma (B-NHL). The study demonstrated an objective response rate (ORR) of 53% among 17 efficacy-evaluable patients, including responses in patients previously treated with CD19-directed chimeric antigen receptor (CAR) T-cell therapy. The maximum tolerated dose (MTD) has not yet been reached. The findings will be presented at the 68th American Society of Hematology (ASH) Annual Meeting, scheduled for December 12–15, 2026, in New Orleans, Louisiana.
IKS03: A Tumour-Activated ADC Approach
IKS03 is a CD19-targeting ADC designed to deliver a highly potent pyrrolobenzodiazepine (PBD) prodrug payload to malignant B cells. The payload is intended to undergo activation and release preferentially within tumour tissue, potentially limiting exposure of healthy tissues to the active cytotoxic agent.
The candidate was licensed from LigaChem Biosciences (formerly LegoChem Biosciences). Its development strategy centres on tumour-selective payload activation, with preclinical studies providing the rationale for clinical evaluation. However, whether this design translates into an improved therapeutic index in patients remains to be established through clinical studies.
Phase 1 Study Design and Patient Population
The first-in-human, multicentre Phase 1 study (NCT05365659) evaluates IKS03 in patients with relapsed or refractory B-NHL who have received at least two previous systemic therapies.
Part I uses a 3+3 dose-escalation design to assess safety and tolerability and establish the MTD and recommended Phase 2 dose. Part II will evaluate the candidate in disease-specific expansion cohorts. The study plans to enrol approximately 140 patients.
As of July 8, 2026, 21 patients, with a median age of 67 years, had received treatment across five dose levels, reaching 3.1 mg/m² (approximately 84 µg/kg). Patients had received a median of four previous treatment lines (range 2–8).
Efficacy was assessed in 17 patients who had completed two treatment cycles across the first four dose levels. This distinction is important because the reported response rate is based on the evaluable population, rather than all 21 treated patients.
Responses Include Patients Previously Treated With CAR-T
Nine of the 17 efficacy-evaluable patients responded, corresponding to an ORR of 53%. Two additional patients achieved stable disease.
Five patients (29%) achieved complete metabolic responses, including two with follicular lymphoma and one each with diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma and T-cell/histiocyte-rich large B-cell lymphoma. Four patients (24%) achieved partial metabolic responses, comprising two patients each with follicular lymphoma and marginal zone lymphoma.
Responses were observed from the lowest dose level, approximately 20 µg/kg, and across all evaluated dose cohorts.
An important finding was the response observed following previous CAR-T therapy. Three of four patients previously treated with CAR-T responded to IKS03. This included a durable complete response in a patient who had received eight previous treatment regimens, including CAR-T therapy and allogeneic transplantation.
Among the eight patients who did not respond, five had Richter-transformed DLBCL, an aggressive lymphoma subtype associated with difficult treatment outcomes.
Responses have lasted up to 14 months, and six of the nine responders eligible for efficacy assessment remained on treatment at the time of the announcement.
Manageable Early Safety Findings
Treatment-related adverse events (TRAEs) occurred in seven of the 21 treated patients. One Grade 4 neutropenia event was identified as the dose-limiting toxicity. It occurred in a patient with follicular lymphoma and bone marrow involvement who had previously received six treatment regimens, including CAR-T therapy. Following resolution, the patient continued treatment and remained in response.
Two Grade 3 neutropenia events were also reported, while the remaining TRAEs were Grade 1–2. No Grade 5 events or treatment-related serious adverse events occurred, and no patient discontinued treatment because of an adverse event. The company also reported no peripheral neuropathy and limited, low-grade non-haematological toxicity.
Although these findings suggest manageable early tolerability, the small safety population and absence of a controlled comparator prevent reliable conclusions about comparative toxicity.
Clinical Interpretation and Development Outlook
The preliminary findings provide an early signal of antitumour activity for IKS03 in a heavily pretreated B-NHL population. The 53% ORR and five complete metabolic responses are notable for a first-in-human study, particularly given the median of four previous treatment lines.
Responses in three of four patients with prior CAR-T exposure are also clinically interesting. They suggest that IKS03 warrants further investigation in patients previously exposed to CD19-directed cellular therapy. However, this small subgroup cannot establish efficacy following CAR-T failure or demonstrate that the ADC overcomes CAR-T resistance.
Several limitations remain. The efficacy analysis includes only 17 patients across multiple lymphoma subtypes, and patients who had not completed two treatment cycles were excluded. Response rates by individual lymphoma subtype and dose level have not been reported. Furthermore, the company has disclosed neither median duration of response nor mature follow-up data.
Dose escalation is continuing, with neither the MTD nor recommended Phase 2 dose established. The company’s comparative safety claims also require validation against appropriately selected clinical datasets.
The updated ASH presentation should provide further insight into the efficacy and safety profile. For now, IKS03 remains an investigational ADC, and the available findings support continued clinical evaluation rather than conclusions about established therapeutic benefit.
Reference
Iksuda to present first clinical data for IKS03 in advanced B-cell non-Hodgkin lymphomas at ASH, Iksuda Therapeutics, 05 November 2026
IKS03 in Patients with Advanced B Cell Non-Hodgkin Lymphomas, ClinicalTrials.gov ID NCT05365659
About the Writer
Charvi Kalal (LinkedIn) is a Pharm.D intern and aspiring medical writer with hands-on experience in medical writing, clinical research, pharmacovigilance, and clinical pharmacy. She has experience in medical content writing through CliMed, along with exposure to ADR monitoring, prescription analysis, patient counselling, literature review, and research documentation. Her research focuses on ADR monitoring and reporting in breast cancer patients receiving targeted therapy. With certifications in GCP, biomedical research, scientific writing, and clinical research, she is passionate about transforming scientific evidence into accurate, engaging, and accessible healthcare content.