US-based Vivace Therapeutics announced the first clinical data from a Phase I clinical trial investigating VT3989 in patients with advanced malignant mesothelioma and other tumours with neurofibromatosis 2 (NF2) mutations.

VT3989 is a first-in-class transcriptional enhanced associate domain (TEAD) autopalmitoylation inhibitor that targets the Hippo pathway.

Presented at the American Association for Cancer Research (AACR) Annual Meeting 2023, the data showed that VT3989 demonstrated antitumour activity in advanced mesothelioma and cancers with NF2 mutations.

The presented trial (NCT04665206) cohort consisted of 43 patients with advanced malignant mesothelioma and 26 with other solid tumours. A total of 37 patients had NF2 mutations. The participants were heavily pre-treated with a median of three prior lines of treatment.

Seven out of 69 patients demonstrated a reduction in tumour size meeting the partial response criteria that persisted up to 21 months while 34 participants had stable disease. Six out of the seven partial responses were observed in mesothelioma participants. Tumour response was also observed in participants with mesothelioma, either with or without the NF2 mutation, and other NF2-mutated solid tumours.

Mesothelioma is a rare type of cancer that develops in the protective tissue layer that covers the majority of internal organs. The primary cause of mesothelioma is asbestos exposure. Around 3,000 people are diagnosed annually and the average life expectancy is 12 to 21 months.

VT3989 was also well tolerated, and no dose-limiting toxicities were observed. The most commonly reported adverse events were a reversible increase of protein albumin in the urine, swelling in the extremities, fatigue, and nausea.

Next steps for Vivace in mesothelioma

The dose optimisation cohorts are now investigating different doses and schedules, which will become the basis of the registration development in patients with mesothelioma. The dose expansion part of the trial will enrol patients into two cohorts based on their cancer indication.

Vivace Therapeutics CEO Sofie Qiao said that the successful translation of preclinical data into humans brings high levels of confidence in the registrational path for VT3989 as a single agent as a treatment for mesothelioma.

Qiao added that VT3989 has the potential to be explored in a combination treatment with targeted therapies to expand clinical utility into major solid tumours.

Vivace Therapeutics first reported preclinical data in last year’s AACR meeting. VT3989 was investigated as a single agent or in combination with AstraZeneca’s Tagrisso (osimertinib). The preclinical EGFR mutant non-small cell lung cancer (NSCLC) models showed enhanced efficacy and delayed tumour growth of VT3989 compared to Tagrisso.