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

Lynne Lederman, PhD
Published Online: 12:57 AM, Sun June 4, 2017

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 Meeting1 and “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.
  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).

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