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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
  1. Robert Wenham1,
  2. Sharad Ghamande2,
  3. Vicky Makker3,
  4. June Hou4,
  5. Linda Duska5,
  6. Daniela Matei6,
  7. Manali Bhave7,
  8. Rachael Scott8,
  9. Natalyn Hawk9,
  10. Tingting Song9 and
  11. Deborah K Armstrong10
  1. 1Moffitt Cancer Center, Tampa, FL
  2. 2Augusta University, Augusta, GA
  3. 3Memorial Sloan Kettering Cancer Center, New York, NY
  4. 4Columbia University Medical Center, New York, NY
  5. 5University of Virginia, Charlottesville, VA
  6. 6Feinberg School of Medicine, Chicago, IL
  7. 7Winship Cancer Institute, Atlanta, GA
  8. 8Eisai Ltd., Hatfield, UK
  9. 9Eisai Inc., Exton, PA
  10. 10Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD


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

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