Mirvetuximab soravtansine shows antitumor activity in platinum resistant ovarian cancer

Mirvetuximab soravtansine demonstrated efficacy and tolerability in patients with platinum resistant ovarian cancer, according to phase 3 clinical data presented at Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.

Previous treatment research has primarily focused on high-grade serous ovarian cancer, Ursula Matulonis, MD, a physician and chief of the division of gynecologic oncology at Dana-Farber Cancer Institute, told Healio. The findings of the current SORAYA study could lead to the approval of the antibody-drug conjugate — comprising a folate receptor alpha-binding antibody, cleavable linker and maytansinoid DM4, a potent tubulin-targeting agent — for use in folate receptor alpha-positive platinum-resistant ovarian cancer (PROC), filling a gap in current treatment.

“If given an accelerated approval, this would be the first targeted therapy [for this indication],” said Matulonis, who is also the Brock-Wilson Family Chair at Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School.

Defining the cohort

Matulonis and colleagues enrolled 106 patients with platinum-resistant high-grade serous ovarian cancer with folate receptor alpha-high expression who had previously received one, two or three lines of therapy including bevacizumab to receive 6 mg/kg of intravenous mirvetuximab soravtansine (MIRV) on the first day a 21-day cycle until disease progression or unacceptable toxicity.

Most participants (51%) had received three lines of prior therapy; 48% had one or two lines. PARP inhibitors were previously used in 48% of participants.

Rate, duration of response

At a median follow-up of 8.5 months, the objective response was observed in 34 participants (objective response rate [ORR], 32.4%; 95% CI, 23.6%-42.2%), with five patients achieving a complete response.

Among participants with one or two previous lines of therapy, the ORR was 35.3% (95% CI, 22.4%-49.9%). In those with three prior lines, the ORR was 30.2% (95% CI, 18.3%-44.3%). The ORR with previous PARP inhibitor treatment was 38% (95% CI, 24.7%-52.8%); without previous PARP inhibitor treatment, it was 27.5% (95% CI, 15.9%-41.7%).

The median duration of response (DOR) was 5.9 months, but because five participants were still on MIRV at the Nov. 16, 2021, data cutoff, the DOR is still changing, the researchers wrote.

Blurred vision, keratopathy and nausea were the most common adverse events and led to dose reductions in 19% of patients, dose delays in 32% and discontinuation in 7%. Only one participant stopped treatment due to an ocular event, according to the abstract.

“This is a drug that is positioned to become a new standard of care for our patients with folate receptor alpha-positive high-grade serous ovarian cancer,” Matulonis said.

Matulonis suggested future research should investigate combining MIRV with other agents, as well as other uses for MIRV.

“I would really like to see this drug expanded into other indications of ovarian cancer treatment,” she said. “That [could mean] using it as [platinum sensitive] maintenance treatment ... When patients complete their platinum-based chemotherapy, they [could] receive this drug as a maintenance drug.”

Reference:

• Conjugate therapy produces remissions in one-third of patients with drug-resistant ovarian cancer, study results show. https://www.dana-farber.org/newsroom/news-releases/2022/conjugate-therapy-produces-remissions-in-one-third-of-patients-with-drug-resistant-ovarian-cancer--study-results-show/. Published March 19, 2022. Accessed March 21, 2022.