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

Abstract

Background: Yttrium-90 FF-21101 (⁹⁰Y-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/m² 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 ⁹⁰Y-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/m² 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: ⁹⁰Y-FF-21101 did not meet the predefined efficacy criteria, and adverse events were consistent with ⁹⁰Y agents. These data may assist in the development of other P-cadherin-directed therapies (ClinicalTrials.gov identifier NCT02454010).

Keywords: FF‐21101; P‐cadherin; ovarian carcinoma; radioimmunotherapy; radiopharmaceutical; solid tumor; yttrium‐90 (90Y).

FIGURE 1

Expansion‐phase study design. (A) objectives and major entry criteria of the ovarian and solid‐tumor expansion‐phase cohorts. (B) Distribution of efficacy‐evaluable patient status in the two cohorts at completion of the study. ECOG indicates Eastern Cooperative Oncology Group; RP2D, recommended phase 2 dose; ⁹⁰Y, yttrium‐90.

FIGURE 2

Progression‐free and overall survival in the ovarian (n = 20) and solid‐tumor (n = 37) expansion‐phase cohorts. (A) Progression‐free survival (in days) was defined as the length of time from the date of the first ⁹⁰Y–FF‐21101 dose to the date of the first objective evidence of progressive disease or death (date of first progressive disease or death − date of first ⁹⁰Y–FF‐21101 dose + 1). For patients with neither progressive disease nor death, progression‐free survival was censored at the date of the last disease‐evaluable assessment. (B) Overall survival (in days) was defined as the length of time from the date of the first ⁹⁰Y–FF‐21101 dose to the date of death from any cause (date of death − date of first ⁹⁰Y–FF‐21101 dose + 1). In surviving patients, overall survival was censored at the date the patient was last known to be alive or the date of last contact. Q 3 months indicates every 3 months; IV, intravenous; ⁹⁰Y, yttrium‐90.