2022-RA-1241-ESGO A multicentre, open-label phase 1/2 trial evaluating the safety, tolerability, and efficacy of morab-202, a folate receptor alpha-targeting antibody-drug conjugate in patients with selected tumour types

Introduction/Background MORAb-202 (farletuzumab ecteribulin) is an antibody-drug conjugate (ADC) comprised of the humanised antifolate receptor-alpha (FRα) monoclonal antibody, farletuzumab, and the cytotoxic microtubule inhibitor, eribulin, conjugated by a cathepsin B-cleavable linker. MORAb-202 targets the eribulin payload to tumour cells expressing FRα, where internalisation leads to lysosomal cleavage of the ADC and intracellular release of eribulin, causing apoptosis, cell-cycle arrest, and bystander effects in adjacent cells. A previous phase 1 study in Japan of MORAb-202 (NCT03386942) demonstrated antitumour activity across multiple tumour types and identified interstitial lung disease (ILD) as an adverse event of interest (Shimizu 2021). An expansion cohort (doses: 0.9, 1.2 mg/kg) in patients with platinum-resistant ovarian cancer (OC) found meaningful efficacy across all FRα-expression levels and ILD/pneumonitis (mainly low grade) was the most common adverse event (Nishio ASCO 2022). Methodology This multicentre phase 1/2 study (NCT04300556) consists of Dose-Escalation and Dose-Confirmation cohorts. In the Dose-Escalation phase, the primary objectives were to evaluate safety/tolerability and determine the recommended phase 2 dose of MORAb-202 in patients with OC, endometrial cancer (EC), non-small cell lung cancer (NSCLC), or triple-negative breast cancer (TNBC). In the ongoing Dose-Confirmation phase, the primary objectives are (1) to further evaluate safety/tolerability and (2) to evaluate preliminary efficacy (ORR) in patients with OC or EC. Based on a population pharmacokinetics model (Hayato ASCO 2022), body-surface-area-based dosing is utilised. The initial cohort will enrol 6 patients at a MORAb-202 25 mg/m2 IV Q3W dose and additional patients will be enrolled at 25 mg/m2 and 33 mg/m2 following ILD safety evaluation. Tumour assessments will be conducted by investigators using RECIST v1.1 at screening, every 6 weeks for 24 weeks, then every 12 weeks or as needed. Potential ILD assessments of CT scans will be conducted by a central ILD expert review board. Results Trial in Progress Conclusion TIP