Mirvetuximab Soravtansine/Carboplatin Improves ORR But Fails to Extend PFS in FRα-High Recurrent Ovarian Cancer

The addition of mirvetuximab soravtansine-gynx (Elahere) to carboplatin did not significantly improve progression-free survival (PFS) compared with platinum-based chemotherapy alone in patients with folate receptor alpha (FRα)–high recurrent ovarian cancer eligible for platinum-based therapy, failing to meet the primary end point of the phase 2 MIROVA/AGO-OVAR 2.34 trial (NCT04274426). However, the combination did produce a substantially higher objective response rate (ORR), according to data presented at the 2026 European Society for Medical Oncology Gynaecological Cancers Congress.¹

The median PFS was 9.53 months (95% CI, 7.20-10.61) with carboplatin plus mirvetuximab soravtansine (n = 75) vs 9.79 months (95% CI, 7.26-11.17) with standard platinum-based chemotherapy (n = 70; HR, 1.0; 95% CI, 0.68-1.46; P = .996). The median follow-up was 8.9 months (IQR, 4.2-12.5) for chemotherapy and 9.2 months (IQR, 6.8-15.1) for the combination.

Furthermore, among evaluable patients, the ORR was 66.2% with the combination (n = 71) vs 32.8% with standard therapy (n = 61). Among evaluable patients with low-grade serous ovarian cancer (LGSOC), the ORR in arm B (n = 7) was 57% compared with 25% in arm A (n = 4). In the chemotherapy arm (n = 20), 90% of these responses were observed during cycles 1 through 6, with 10% occurring during the maintenance phase. In the combination arm (n = 47), 85.1% of responses occurred during the chemotherapy phase and 14.9% during maintenance. Responses were observed across histologic subtypes in both arms.

Of note, primary data from MIROVA were initially shared at the 2026 American Society of Clinical Oncology Annual Meeting.²

"The combination of carboplatin plus mirvetuximab [soravtansine] in this biomarker-defined patient population was feasible and shows a high response rate, but this does not translate into prolonged PFS. However, we do see a response to [the combination] across different histologies and high response rates in LGSOC, which warrants further investigation," said Fabian Trillsch, MD, presenting author and deputy director of the Clinic and Polyclinic for Gynecology and Obstetrics at LMU University Hospital in Munich, Germany.

The ongoing phase 3 GOG-3078/ENGOT-ov76/GLORIOSA trial (NCT05445778), which is enrolling a more homogeneous patient population with respect to the number of prior treatment lines and histology, is expected to provide further insight into the role of mirvetuximab soravtansine in the platinum-eligible recurrent ovarian cancer setting, Trillsch noted.¹

How was the MIROVA trial designed?

MIROVA/AGO-OVAR 2.34 is a randomized phase 2 study evaluating the feasibility and efficacy of mirvetuximab soravtansine in combination with carboplatin in patients with platinum-eligible recurrent ovarian cancer. Platinum eligibility was defined as a treatment-free interval with platinum (TFIp) of more than 3 months, provided there was a prior response to platinum. Eligible patients were required to have recurrent epithelial cancer of the ovary, fallopian tube, or peritoneum; FRα-high status defined as at least 75% of tumor cells with FRα membrane staining and at least 2+ intensity using the Ventana FOLR1 (FOLR1 2.1) CDx assay; at least 1 prior line of chemotherapy; measurable disease or evaluable disease in combination with GYNECOLOGIC Cancer Intergroup (GCIG) CA-125 criteria; and ineligibility for bevacizumab (Avastin). Prior PARP inhibitor treatment was mandatory for patients with BRCA-mutated tumors. All histologic subtypes were permitted.

Patients were randomly assigned 1:1 to either of the following:

• Arm A: Carboplatin plus pegylated liposomal doxorubicin, carboplatin plus gemcitabine, or carboplatin plus paclitaxel for up to 6 cycles, followed by observation or PARP inhibitor maintenance, according to local standard
• Arm B: Carboplatin plus mirvetuximab soravtansine at 6 mg/kg adjusted ideal body weight for up to 6 cycles, followed by mirvetuximab soravtansine maintenance monotherapy at the same dose level

Stratification factors included the number of prior chemotherapy lines (1-2 vs ≥ 3), platinum-free interval (> 3-6 months vs 6-12 months vs > 12 months), and BRCA mutation status (mutant vs wild-type). The study’s primary end point was PFS per RECIST 1.1 criteria by investigator assessment. Key secondary end points included ORR, time to first subsequent therapy (TFST), time to subsequent therapy (TSST), overall survival (OS), and patient-reported quality of life.

What were the patient characteristics and treatment exposure?

Baseline characteristics were generally balanced between arms. The mean age was 61.5 years in arm A and 62.5 years in arm B. High-grade serous ovarian cancer was the predominant histology at 85.7% and 81.3%, respectively, whereas LGSOC accounted for 8.6% and 9.3% of patients in these respective groups. BRCA wild-type status was present in 87.1% and 84% of patients, respectively. More than two-thirds of patients in both arms had a platinum-free interval exceeding 12 months (67.1% vs 66.7%). Prior carboplatin and taxane were received by all patients, bevacizumab by 75.7% and 78.7%, and PARP inhibitors by 70% and 64%, respectively.

What did the secondary efficacy analyses show?

The median TFST was 12.91 months (95% CI, 10.45-20.80) in arm B vs 10.87 months (95% CI, 8.25-13.34) in arm A (HR, 0.64; 95% CI, 0.41-0.98; P = .04). TSST was also significantly longer in arm B, at a median of 25.36 months (95% CI, 19.19-not available) vs 19.45 months (95% CI, 15.80-25.07) in arm A (HR, 0.57; 95% CI, 0.32-0.99; P = .048).

OS data were assessed using a restricted mean survival analysis due to crossing of the Kaplan-Meier curves. The restricted mean OS was 26.74 months (95% CI, 23.06-30.42) in arm B vs 24.59 months (95% CI, 20.84-28.33) in arm A, translating to a difference of 2.15 months (95% CI, −3.10 to 7.40; P = .422). OS maturity was 48.3% at the December 3, 2025, data cutoff. The median follow-up for OS was 15.4 months (IQR, 8.8-25.5) in arm A and 18.0 months (IQR, 12.7-24.2) in arm B. Notably, 35.7% of patients in arm A crossed over to receive mirvetuximab soravtansine following completion of study treatment.

“[Though these differences were not] reliably statistically significant, at least this suggests that there's no potential negative effect of mirvetuximab [on the] feasibility and activity of subsequent therapies,” Trillsch added.

What did the safety analysis show?

In the safety population, 71.4% of patients in arm A (n = 63) and 86.5% in arm B (n = 74) completed at least 6 cycles of platinum-based therapy. The median number of cycles was 6 in both arms. Mirvetuximab soravtansine maintenance was received by 79.7% of patients in arm B, while PARP inhibitor maintenance was received by 42.9% of patients in arm A. Discontinuations for reasons other than disease progression were lower in arm B than arm A (10.8% vs 30.2%). The median duration of treatment from randomization was 7.82 months in arm B and 11.1 months in arm A.

The regimen’s adverse effect (AE) profile was consistent with the known profiles of the individual agents, according to Trillsch. Regarding hematologic toxicities, the rate of anemia was 41% in arm A and 22% in arm B (grade ≥ 3: 21% vs 5.4%); thrombocytopenia was observed in 35% vs 47% (grade ≥ 3: 22% vs 16.3%), and neutropenia was reported in 40% vs 26% (grade ≥ 3: 30% vs 13.5%). The incidence of febrile neutropenia was 3% in arm A and 0% in arm B.

Regarding nonhematologic toxicities, the incidence of nausea was 35% in arm A and 53% in arm B (grade ≥ 3: 1.4% vs 1.4%). Peripheral neuropathy occurred in 11% vs 53%, respectively (grade ≥ 3: 1.4% vs 4.1%), representing a notable increase with the mirvetuximab soravtansine combination. Urogenital tract infections were reported in 30% vs 38% (grade ≥ 3: 6.8% vs 2%), and any-grade interstitial lung disease in 0% vs 6% of patients (grade ≥ 3: 1.4%). Thrombosis/embolism was reported in 6% vs 10% (grade ≥ 3: 3% vs 5.4%).

As expected with mirvetuximab soravtansine, ocular toxicity was prominent in arm B. Blurred vision occurred in 2% vs 49% of patients in arm A vs arm B, keratopathy in 0% vs 28% (grade ≥ 3: 6.8%), and other ocular events in 6% vs 27%. Overall, the incidence of serious AEs in the chemotherapy phase was 73.8% in arm A and 51.3% in arm B; in the maintenance phase, these respective rates were 26.2% and 48.7%.

Disclosures: Trillsch disclosed advisory board fees (personal) from AbbVie, AstraZeneca, Corcept Therapeutics, GSK, Eisai, and MSD; speaker fees and honoraria (personal) from AbbVie, AstraZeneca, GlaxoSmithKline, Medudy, MSD, and Regeneron; travel support (personal) from AbbVie, AstraZeneca, and GSK; and research funding (institutional) from AstraZeneca, Regeneron, and SAGA Diagnostics.

References

1. Trillsch F, Heitz F, Marmé F, et al. A randomized phase II trial of mirvetuximab soravtansine, in folate receptor alpha (FRα) high recurrent ovarian cancer eligible for platinum-based chemotherapy (MIROVA/AGO-OVAR 2.34). Presented at: 2026 ESMO Gynaecological Cancers Congress; June 17-19, 2026; Copenhagen, Denmark. Abstract 108O.
2. Harter P, Heitz F, Marmé F, et al. A randomized phase II trial of mirvetuximab soravtansine in folate receptor alpha (FRα)–high recurrent ovarian cancer eligible for platinum-based chemotherapy (MIROVA/AGO-OVAR 2.34). J Clin Oncol. 2026;44(suppl 16):5506. doi:10.1200/JCO.2026.44.16_suppl.5506