DeuterOncology, a clinical-stage biotech company developing deuterated cancer therapies, has shared updated results from its ongoing Phase 1 study of DO-2, a MET tyrosine kinase inhibitor, at the World Conference on Lung Cancer (WCLC) 2025 in Barcelona (Abstract ID-2859).

DO-2 has completed enrolment in a Phase 1 dose escalation study including 29 patients with advanced solid tumours, 86% of whom had non-small cell lung cancer (NSCLC). All patients had tumours with known driver alterations. Among 26 evaluable patients, 10 had MET exon 14 skip mutation-positive NSCLC without other oncogenic drivers. At doses reaching preclinically defined thresholds, all 10 patients showed tumour shrinkage and a 100% disease control rate. Partial responses, defined as more than 30% reduction in tumour size, were seen in 2 of these patients.

Cecilia Ahlin, DeuterOncology’s CMO, said: “These results represent a significant advancement in MET-targeted therapy. Our deuteration strategy has successfully enhanced drug exposure while maintaining efficacy, but most importantly, we have achieved this without the debilitating peripheral oedema that forces many patients to discontinue current MET inhibitors. This addresses a critical unmet medical need for cancer patients.”

The study reported a markedly improved safety profile. Only one patient experienced grade 1 peripheral oedema, compared with 68–82% of patients treated with other MET inhibitors. No grade 3 or 4 oedema occurred. Overall tolerability was strong, with just two grade 3 treatment-related events, fatigue and reversible creatinine increase.

Deuteration improved plasma exposure compared with the non-deuterated parent compound, enabling once-daily dosing of 60mg with food. By contrast, approved MET inhibitors typically require higher daily doses of 450–800mg. The data also indicate that continuous 24/7 MET inhibition may not be necessary for efficacy but contributes to the class-effect toxicity of peripheral oedema. DO-2’s pharmacokinetic profile allows effective target engagement while giving recovery periods that reduce on-target toxicities.

Dr Hans Prenen, principal investigator at University Hospital Antwerp, commented: “The clinical data for DO-2 are very encouraging. The fact that we are seeing robust anti-tumour activity with minimal peripheral oedema represents a potential game-changer for MET-driven lung cancer patients, who currently face difficult treatment tolerability issues with existing therapies.”

Based on these results, DeuterOncology has started an expansion cohort in selected first-line MET exon 14 skip NSCLC patients to further assess the safety and efficacy of the 60mg once-daily regimen.