Pooled Data of Mirvetuximab Soravtansine in Platinum-Resistant Ovarian Cancer Show Promise

Kathleen N. Moore, MD

Mirvetuximab soravtansine (IMGN853), a folate receptor alpha-targeting antibody-drug conjugate, showed promising activity in patients with platinum-resistant ovarian cancer who had received 1 to 3 prior lines of therapy. According to Kathleen N. Moore, MD, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, pooled data presented in a poster at the 2017 ASCO Annual Meeting¹and “our prior published phase I data support this exploration with high confirmed response rates, much higher than we see with standard chemotherapy alone, a very tolerable side effect profile, and durable response rates with a median of close to 7 months.”

Elevated levels of folate receptor alpha are seen in 80% of recurrent ovarian cancers. Mirvetuximab soravtansine combines a folate receptor alpha-binding antibody linked to the tubulin-disrupting maytansinoid DM4. This agent has shown against advanced epithelial ovarian cancer, including disease that is platinum-resistant. These patients have a poor prognosis and have unmet medical needs for effective therapy. The standard of care agents currently used as monotherapy in this patient population yield low response rates and a progression-free survival (PFS) of only 3 to 4 months.

The primary objective of this study was to evaluate the safety and efficacy of mirvetuximab soravtansine in a pooled analysis of patients with epithelial ovarian cancer across 3 expansion cohorts of a phase I clinical trial (NCT01609556). It included patients who met the eligibility criteria for the pivotal phase III study of mirvetuximab soravtansine (FORWARD I; NCT02631876), that is, platinum-resistant disease, medium-to-high levels of folate receptor alpha expression, and 1 to 3 prior lines of therapy. The FORWARD I study is an ongoing, randomized, phase III study of mirvetuximab monotherapy versus investigator’s choice of chemotherapy with PFS as the primary endpoint (NCT02631876).²

In the study, patients received mirvetuximab soravtansine at 6 mg/kg every 3 weeks until disease progression, adverse event, or investigator or patient decision. Eligibility criteria for the 3 expansion cohorts were: platinum-resistant cohort: up to 5 prior lines of therapy with measurable disease; ovarian biopsy cohort: tumor can be biopsied, platinum sensitive or resistant, measurable or non-measurable disease, any number of prior lines of therapy; and for the corticosteroid eye drop cohort: recurrent disease, regardless of platinum sensitivity, measurable or non-measurable disease, and 3 to 4 prior lines of therapy.

There were 113 patients in the pooled population, of whom 36 were FORWARD I eligible. Patients had a median of 3 prior lines of therapy; 85% of patients in the pooled population had platinum-resistant disease. All patients had received prior platinum compounds and taxanes; over half had received bevacizumab, and about a fifth (22%) had received a PARP inhibitor. In the pooled population, folate receptor alpha expression was low in 20%, medium in 26%, and high in 54%.

The confirmed overall response rate (ORR) was 30% in all pooled patients (95% CI, 22-39), and included 3 complete responses and 31 partial responses; in the FORWARD I eligible group confirmed ORR was 47% (95% CI, 30-65), including 1 complete response and 16 partial responses. Median PFS was 4.3 months in the pooled group (95% CI, 3.9-5.4) and 6.7 months (95% CI, 4.1-8.3) in the FORWARD I eligible group. Duration of response was 19.3 weeks and 25.1 weeks in these groups, respectively.

Mirvetuximab soravtansine was well tolerated across all cohorts. Adverse events were generally grade 1 or 2 and manageable. The most common adverse events included diarrhea, fatigue, nausea, and blurred vision. Nine percent of patients discontinued due to drug-related adverse events.

Moore said the first indication for mirvetuximab soravtansine may be in a high unmet need population of patients with platinum-resistant disease and then moving forward in combination therapy.

“Whether or not it can be moved into platinum-sensitive or front-line populations remains to be seen,” said Moore.

References:

1. Moore KN, Matulonis UA, O’Malley DM, et al. Mirvetuximab soravtansine (IMGN853), a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in platinum-resistant epithelial ovarian cancer (EOC) patients (pts): Activity and safety analyses in phase I pooled expansion cohorts.J Clin Oncol.35, 2017 (suppl; abstr 5547).
2. Moore KN, Vergote I, Oaknin, A, et al. FORWARD I (GOG 3011): A randomized phase 3 study to evaluate the safety and efficacy of mirvetuximab soravtansine (IMGN853) versus chemotherapy in adults with folate receptor alpha (FRα)-positive, platinum-resistant epithelial ovarian cancer (EOC), primary peritoneal cancer, or primary fallopian tube cancer.J Clin Oncol.35, 2017 (suppl; abstr TPS5607).