Kathleen N. Moore, MD
Mirvetuximab soravtansine (IMGN853), an experimental antibody–drug conjugate (ADC) developed for folate receptor alpha (FRα)-positive cancers, demonstrated a manageable safety profile and clinical activity in the treatment of patients with platinum-resistant ovarian cancer, according to the results of a phase I expansion study published in the Journal of Clinical Oncology
The confirmed objective response rate (ORR) for all evaluable patients was 26% (95% CI, 14.3-41.1), including 1 complete and 11 partial responses. The median progression-free survival (PFS) was 4.8 months, and the median duration of response was 19.1 weeks.
“Notably, in the subset of  patients who had received 3 or fewer prior lines of therapy, an ORR of 39%, PFS of 6.7 months, and duration of response of 19.6 weeks were observed,” corresponding study author Kathleen N. Moore, MD, Stephenson Oklahoma Cancer Center, and her coauthors wrote.
The study included 46 patients with histologically confirmed epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer who had experienced progression or relapse within 6 months of completing prior platinum-based therapy. The median patient age was 62.5 years (range 41-81 years), and the distribution of primary tumor types was primarily epithelial ovarian carcinoma (94%), fallopian tube cancer (4%), and peritoneal cancer (2%). The majority of patients with epithelial ovarian cancer (84%) presented with serous histology.
All eligible patients were heavily pretreated, with 100% having been previously exposed to platinum and taxane therapies. Eleven patients (24%) had received only 1 prior platinum regimen, with the remaining 35 patients (76%) having received at least 2 lines of platinum-based therapy. One half of the study population (n = 23) had received between 1 and 3 previous systemic therapies, and the other half had received 4 or 5 previous lines.
Patients were administered 6.0 mg/kg of mirvetuximab soravtansine (previously established as the recommended phase II dose) intravenously once every 3 weeks, until they experienced intolerable toxicity or disease progression. The median duration of treatment with mirvetuximab soravtansine was 3.8 months, and the median follow-up period was 5.5 months.
As part of the analyses, the study authors sorted patients based on FRα positivity (by IHC of archival tissue samples) into the following categories: low (25% to 49% of tumor cells with ≥2+ staining intensity), medium (50% to 74% of cells with ≥2+ intensity), or high (≥75% of cells with ≥2+ intensity). Regardless of FRα expression, a majority of patients experienced tumor shrinkage in response to treatment with mirvetuximab soravtansine.
Additionally, the researchers in this study identified a potential relationship between response to treatment and the number of prior lines of therapy. The ORR for those who had received 1 to 3 prior lines of therapy was 39% (95% CI, 19.7-61.5), compared with 13% (95% CI, 2.8-33.6) in patients who had received 4 or more lines of therapy. The median PFS was 4.8 months (95% CI, 3.9-5.7 months) for the total population, 6.7 months (95% CI, 3.9-8.7 months) for the cohort of patients who had received 1 to 3 previous lines of therapy, and 3.9 months (95% CI, 2.6-5.4 months) for those who had received 4 or more prior lines.
Adverse events were generally mild (≤ grade 2) among the 46 patients enrolled in the study. The most commonly observed treatment-related toxicities were diarrhea (44%), blurred vision (41%), nausea (37%), and fatigue (30%), neuropathy (28%), keratopathy (26%), increased AST (24%), and vomiting (22%). The majority of these events were grade 1 or 2.
Twelve patients (26%) experienced a grade 3 event, the most frequent of which were fatigue and hypotension (both 4%). One patient experienced grade 4 febrile neutropenia and septic shock, though this was resolved after withdrawal from the study. Additional adverse events that led to study discontinuation involved individual cases of low-grade ocular disorders (grade 1 eye pain, corneal cysts, and grade 2 blurred vision), grade 2 pneumonitis, grade 3 hypersensitivity, and grade 3 myelodysplastic syndrome.
Serious treatment-related adverse events were observed in 11 patients (22%), with no individual events being observed for more than 1 patient. No fatalities related to adverse events were observed.
Based on these study results, a randomized phase III trial comparing the safety and efficacy of mirvetuximab soravtansine with physicians’ choice of chemotherapy in platinum-resistant patients with 3 or fewer previous therapies and medium or high FRα expression is currently ongoing (FORWARD I; NCT02631876).
Moore KN, Martin LP, O’Malley DM, et al. Safety and activity of mirvetuximab soravtansine (IMGN853), a folate receptor alpha-targeting antibody-drug conjugate, in platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer: a phase I expansion study [published online December 28, 2016]. J Clin Oncol. doi:10.1200/JCO.2016.69.9538.