Mirvetuximab Soravtansine Shows Promise in Ovarian Cancer

Data from phase I pooled expansion cohorts showed that mirvetuximab soravtansine (IMGN853) induced a solid response rate in patients with platinum-resistant ovarian cancer who had received 1 to 3 prior lines of therapy.

Kathleen N. Moore, MD

Data from phase I pooled expansion cohorts showed that mirvetuximab soravtansine (IMGN853), a folate receptor alpha-targeting antibody-drug conjugate, induced a solid response rate in patients with platinum-resistant ovarian cancer who had received 1 to 3 prior lines of therapy.

Patients with platinum-resistant epithelial ovarian cancer were selected from 3 expansion cohorts of an ongoing phase I trial (N = 113), including 36 who met the eligibility criteria for FORWARD I, a pivotal phase III study of mirvetuximab soravtansine. FORWARD I is an ongoing, randomized, phase III study of mirvetuximab monotherapy versus investigator’s choice of chemotherapy. The primary endpoint is progression-free survival (PFS). Patients are eligible FORWARD I if they have platinum-resistant disease, medium-to-high levels of folate receptor alpha expression, and 1 to 3 prior lines of therapy.

In all pooled patients from the phase I analysis, the confirmed overall response rate (ORR) was 30% (95% CI, 22-39), and included 3 complete responses and 31 partial responses. Confirmed ORR was 47% (95% CI, 30-65) in the group eligible for FORWARD I, including 1 complete response and 16 partial responses.

Median PFS was 4.3 months in the pooled group (95% CI, 3.9-5.4) with 19.3-week duration of response. Median PFS was 6.7 months (95% CI, 4.1-8.3) in the FORWARD I eligible group with a duration of response of 25.1 weeks.

Kathleen N. Moore, MD, assistant professor in the section of gynecologic oncology and director of the Oklahoma TSET Phase I Clinical Trials Program at the University of Oklahoma Health Sciences Center, presented the results in a poster at the 2017 ASCO Annual Meeting.

“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,” she said in an interview with OncLive.

Four in 5 recurrent ovarian cancers display elevated levels of folate receptor alpha. 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 PFS of only 3 to 4 months.

Mirvetuximab soravtansine combines a folate receptor alpha-binding antibody linked to the tubulin-disrupting maytansinoid DM4. This drug has shown activity against advanced epithelial ovarian cancer, including platinum-resistant disease.

In this study, patients received 6 mg/kg mirvetuximab soravtansine 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;
  • corticosteroid eye drop cohort—recurrent disease, regardless of platinum sensitivity, measurable or non-measurable disease, and 3 to 4 prior lines of therapy.

Patients had a median of 3 prior lines of therapy, and 85% of patients in the pooled population had platinum-resistant disease. All patients had received prior treatment with platinum compounds and taxanes, more than half had received bevacizumab (Avastin), and 22% had received a PARP inhibitor. In the pooled population, folate receptor alpha expression was low in 20% of patients, medium in 26%, and high in 54%.

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

Moore added that 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,” she said.

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).