The antibody-drug conjugate (ADC) mirvetuximab soravtansine boosts tumor response when added to standard chemotherapy for patients with platinum-sensitive ovarian cancer, but it does not improve their survival outcomes, according to a phase 2 trial.

Mirvetuximab is currently approved as monotherapy for patients with platinum-resistant ovarian cancer that’s folate receptor (FR) alpha-positive after they’ve received one to three prior systemic therapies. In that setting, the ADC was shown to increase median overall survival by about 4 months compared with chemotherapy.

The new trial, MIROVA/AGO-OVAR 2.34, looked at whether adding mirvetuximab to carboplatin could benefit patients with recurrent FR alpha-high ovarian cancer that was platinum-sensitive. It found that even though the combination doubled tumor response rates, it had no impact on progression-free survival — the trial’s primary endpoint — or overall survival.

The mechanisms underlying the disconnect between tumor response and survival outcomes are unclear, said investigator Fabian Trillsch, of Ludwig-Maximilians-Universität München in Munich, Germany.

“What we know is that continuing the ADC following initial response did not translate to progression-free survival benefits,” Trillsch told Medscape Medical News.

But the findings, presented at the ESMO Gynecological (ESMO Gyn) Cancers Congress 2026 in Copenhagen, Denmark, are far from the final word on mirvetuximab in treating platinum-sensitive ovarian cancer. Other studies, including the phase 3 GLORIOSA trial, are ongoing and may show the way forward, experts said. 

Adding an ADC to Chemotherapy

MIROVA enrolled patients with recurrent ovarian cancer with confirmed high FR alpha expression and prior response to carboplatin. Most of the patients (77%) had already received treatment with bevacizumab, while 67% had received a PARP inhibitor (required for trial patients with BRCA-mutated tumors).

The researchers randomized 145 patients to either six cycles of carboplatin (with paclitaxel, gemcitabine, or pegylated liposomal doxorubicin) followed by maintenance PARP inhibition or observation, or to carboplatin plus mirvetuximab (6 mg/kg adjusted ideal body weight every 3 weeks) followed by mirvetuximab maintenance.

About 39% of patients in the standard carboplatin arm received PARP inhibitor maintenance. In the combination arm, 79% completed mirvetuximab maintenance.

The addition of the ADC doubled the objective response rate, from roughly 33% to 66% (P < 0.001). But median progression-free survival was unchanged, at 9.5 months in the combination arm vs 9.8 months in the standard arm (P = 0.996). Median overall survival was also comparable between the combination and standard arms (26.7 months vs 24.6 months; P = 0.422).

Trillsch noted that overall survival data maturity at the time of analysis was 48%, and there was “significant crossover,” with about 36% of patients in the standard arm receiving mirvetuximab after study treatment.

As for safety, ocular toxicity — including blurred vision and keratopathy — was the most common adverse event with the combination treatment. Over 80% of patients developed ocular side effects of any grade, making collaboration with ophthalmology colleagues essential with mirvetuximab treatment, Trillsch said.

Other common adverse events with the combination included peripheral neuropathy (53%), thrombocytopenia (47%), nausea (41%), and infections (38%). Grade 1 to 3 pneumonitis was reported in four patients.

Trillsch told Medscape Medical News that “almost all toxicity” resolved with management recommended in the trial protocol.

Questions Going Forward

Study discussant Giuseppe Caruso, MD, PhD, of the European Institute of Oncology in Milan, Italy, offered some potential reasons why mirvetuximab plus carboplatin did not improve survival outcomes.

In an interview, he pointed to certain trial design factors, such as the heterogeneous population, which included patients with non-high-grade serous histotypes, patients with platinum-free intervals as short as 3-6 months, and those with three or more prior lines of therapy.

Caruso also noted that outcomes in the standard chemotherapy arm were better than anticipated, with a median progression-free survival of 9.8 months vs an assumed 7 months.

Trillsch said that GLORIOSA, which is studying a more homogeneous group of patients with platinum-sensitive disease, is expected to provide further insights.

For his part, Caruso believes there will ultimately be a role for ADCs in platinum-sensitive ovarian cancer, and he agreed that ongoing studies will shed light on how to incorporate them.

He noted that as PARP inhibitors are increasingly used in the first-line maintenance setting, the landscape around subsequent treatment is shifting. After PARP inhibitor treatment, patients show a reduced response to platinum rechallenge, making a strong case for evaluating alternative strategies earlier in the disease course.

During his discussion, Caruso highlighted three broad strategies that studies are currently investigating: the consolidation approach used in MIROVA (an ADC plus platinum, followed by ADC maintenance); a switch or intensification strategy, like that under study in GLORIOSA (standard chemotherapy doublet followed by ADC maintenance, with or without bevacizumab); and a replacement strategy (ADC with or without bevacizumab instead of chemotherapy, primarily in patients who progress during PARP inhibitor therapy).

“We need to understand which one is best and when,” Caruso said.

However, he did sound a note of caution about ADC resistance, given that existing ADCs have the same payload. “We are trying to overcome platinum and PARP [inhibitor] resistance,” Caruso noted, “but be careful, because we are already entering, I think, the era of ADC resistance.”

MIROVA was funded by AbbVie. Trillsch reported financial relationships with AbbVie, AstraZeneca, GSK, and other companies. Caruso reported financial relationships with AbbVie, AstraZeneca, GSK, and others.