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Novel ADC Promising in Tough-to-Treat Ovarian Cancer

— Ocular AEs an issue with mirvetuximab in folate receptor alpha-high platinum-resistant disease

MedpageToday

PHOENIX -- Mirvetuximab soravtansine monotherapy demonstrated anti-tumor activity in previously treated patients with folate receptor alpha (FRα)-high platinum-resistant ovarian cancer, a researcher said here.

In the phase III SORAYA trial, treatment with the investigational mirvetuximab resulted in an objective response rate (ORR) of 32.4% (95% CI 23.6%-42.2%) in 106 patients, all of whom received prior bevacizumab (Avastin), reported Ursula Matulonis, MD, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston.

"These results position mirvetuximab to become a practice-changing, biomarker-driven standard-of-care treatment option for patients with FRα-positive platinum-resistant ovarian cancer," Matulonis said at the Society of Gynecologic Oncology (SGO) meeting.

Mirvetuximab soravtansine is a first-in-class antibody drug conjugate targeting FRα, which has demonstrated activity in some patients with FRα-high platinum-resistant and platinum-sensitive ovarian cancer. In May 2019, developer ImmunoGen suffered a when its first phase III trial of the agent failed to offer a boost in progression-free survival (PFS) versus chemotherapy, and the FDA recommended the developer conduct a in patients with high FRα expression, according to Fierce Biotech.

The most common treatment-related adverse events (TRAEs) in the current trial were ocular events, with keratopathy of all grades occurring in 36% of patients, and blurred vision in 41%. Patients were instructed to use prophylactic lubricating and steroid eye drops. All patients received a baseline ocular exam, and those with ocular symptoms subsequently underwent exams every 2 cycles until the end of treatment.

These ocular events were reversible and managed with protocol-defined dose modifications, Matulonis reported, with one patient discontinuing therapy due to grade 4 keratopathy, which resolved within 15 days.

SGO discussant Deborah K. Armstrong, MD, of Johns Hopkins Kimmel Cancer Center in Baltimore, noted that the need for anticipated ocular prophylaxis and ophthalmological care demonstrated in SORAYA "may be a hurdle in low-resource settings."

She also questioned what percentage of patients with platinum-resistant ovarian cancer will meet the definition of FRα used in the trial. "This outlines the need for a consistent, reproducible, and user-friendly assay or biomarker for FRα expression and for the definition of FRα high," she said.

The SORAYA trial enrolled 106 patients (median age 62; 80% with epithelial ovarian cancer; 59% stage III) with high levels of FRα expression. They had a median of three prior lines of therapy, with 51% having three prior lines and 48% one or two prior lines. All patients received prior bevacizumab, while 48% of patients received a prior PARP inhibitor.

Patients received IV mirvetuximab at 6 mg/kg, using adjusted ideal body weight, once every 3 weeks until disease progression or intolerable side effects.

Confirmed objective responses by investigators were seen in 34 of 105 evaluable patients, including five complete responses (CRs). The ORR by blinded independent central review (BICR) was 31.6% (95% CI 22.4%-41.9%), including five CRs.

"The response rate is nearly triple the benchmark set in prior studies of less heavily pretreated platinum-resistant ovarian cancer populations," Matulonis reported.

ORRs by investigator were consistent regardless of number of prior lines of therapies or prior PARP inhibitor:

  • 1-2 prior lines of therapy: 35.3% (95% CI 22.4%-49.9%)
  • 3 prior lines of therapy: 30.2% (95% CI 18.3%-44.3%)
  • Prior PARP inhibitor exposure: 38.0% (95% CI 24.7%-52.8%)
  • No prior PARP inhibitor exposure: 27.5% (95% CI 15.9%-41.7%)

The median duration of response was 6.9 months (95% CI 5.6-8.1) by investigators as of the March 3, 2022 data cut-off. Duration of response by prior therapy was 5.9 months for patients with one to two lines of prior therapy, 7.0 months for patients with three lines of therapy, 5.7 months for patients with prior PARP inhibitor exposure, and 5.9 months for those without prior PARP inhibitor exposure.

The median PFS was 4.3 months (95% CI 3.7-5.1) by investigator and 5.5 months (95% CI 3.8-6.9) by BICR.

TRAEs led to dose reductions in 19% of patients, dose delays in 32% of patients, and discontinuations in 7% of patients. One death due to respiratory failure was recorded as possibly related to mirvetuximab, but autopsy review showed the patient had lung metastases, bronchopneumonia, and no evidence of drug reaction, according to Matulonis.

  • author['full_name']

    Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.

Disclosures

The study was funded by ImmunoGen. Some co-authors are company employees.

Matulonis disclosed relationships with Novartis, AstraZeneca, Merck, GlaxoSmithKline, Trillium, Blueprint Medicines, Agenus, ImmunoGen, NextCure, Ovarian Cancer Research Alliance, Rivkin Foundation, Clearity, Symphogen, Alkermes, and Advaxis.

Primary Source

Society of Gynecologic Oncology

Matulonis U, et al "Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: results from the SORAYA study" SGO 2022; Abstract LBA 4.