A trial of radiolabeled antibody yttrium-90-FF-21101 for the treatment of advanced ovarian and other cancers.

Background: Yttrium-90 FF-21101 (Y-FF-21101) is a radiopharmaceutical that targets P-cadherin as a therapy against solid tumors. A previously reported, first-in-human study determined that a dose of 25 mCi/m was safe, and a patient with clear cell carcinoma of the ovary achieved a complete response. In this article, the authors report the results of Y-FF-21101 treatment in an ovarian carcinoma expansion cohort and in patients with selected solid tumors who had known high P-cadherin expression.

Methods: The trial was conducted as an open-label study in patients with advanced/metastatic disease. Radiologic response and safety were evaluated in patients who received 25 mCi/m intravenously once every three cycles of 28 days until they developed progressive disease. Evaluation of the ovarian cohort was conducted in a Simon two-stage manner to determine further enrollment.

Results: Fifty-seven patients (20 with ovarian carcinoma) were enrolled and treated. Patients who had ovarian and solid tumors had received a median of five and three prior therapies, respectively. No complete or partial responses were observed, so the trial was ended. The median progression-free survival was 118 days for the ovarian cohort and 55 days for the solid-tumor cohort. The most common treatment-related adverse events were thrombocytopenia (40%) and neutropenia (54%). One patient each developed fatal veno-occlusive disease and intracranial hemorrhage. Patients with higher P-cadherin levels remained on the study longer.

Conclusions: Y-FF-21101 did not meet the predefined efficacy criteria, and adverse events were consistent with Y agents. These data may assist in the development of other P-cadherin-directed therapies (ClinicalTrials.gov identifier NCT02454010).