Novel ADC Promising in Tough-to-Treat Ovarian Cancer

Novel ADC Promising in Robust-to-Deal with Ovarian Most cancers

PHOENIX — Mirvetuximab soravtansine monotherapy demonstrated anti-tumor exercise in beforehand handled sufferers with folate receptor alpha (FRα)-high platinum-resistant ovarian most cancers, a researcher mentioned right here.

Within the section III SORAYA trial, therapy with the investigational mirvetuximab resulted in an goal response fee (ORR) of 32.4% (95% CI 23.6%-42.2%) in 106 sufferers, all of whom obtained prior bevacizumab (Avastin), reported Ursula Matulonis, MD, of the Dana-Farber Most cancers Institute and Harvard Medical College, each in Boston.

“These outcomes place mirvetuximab to grow to be a practice-changing, biomarker-driven standard-of-care therapy possibility for sufferers with FRα-positive platinum-resistant ovarian most cancers,” Matulonis mentioned on the Society of Gynecologic Oncology (SGO) assembly.

Mirvetuximab soravtansine is a first-in-class antibody drug conjugate concentrating on FRα, which has demonstrated exercise in some sufferers with FRα-high platinum-resistant and platinum-sensitive ovarian most cancers. In Might 2019, developer ImmunoGen suffered a setback when its first section III trial of the agent failed to supply a lift in progression-free survival (PFS) versus chemotherapy, and the FDA advisable the developer conduct a brand new section III trial in sufferers with excessive FRα expression, based on Fierce Biotech.

The commonest treatment-related opposed occasions (TRAEs) within the present trial have been ocular occasions, with keratopathy of all grades occurring in 36% of sufferers, and blurred imaginative and prescient in 41%. Sufferers have been instructed to make use of prophylactic lubricating and steroid eye drops. All sufferers obtained a baseline ocular examination, and people with ocular signs subsequently underwent exams each 2 cycles till the top of therapy.

These ocular occasions have been reversible and managed with protocol-defined dose modifications, Matulonis reported, with one affected person discontinuing remedy on account of grade 4 keratopathy, which resolved inside 15 days.

SGO discussant Deborah Okay. Armstrong, MD, of Johns Hopkins Kimmel Most cancers Middle in Baltimore, famous that the necessity for anticipated ocular prophylaxis and ophthalmological care demonstrated in SORAYA “could also be a hurdle in low-resource settings.”

She additionally questioned what share of sufferers with platinum-resistant ovarian most cancers will meet the definition of FRα used within the trial. “This outlines the necessity for a constant, reproducible, and user-friendly assay or biomarker for FRα expression and for the definition of FRα excessive,” she mentioned.

The SORAYA trial enrolled 106 sufferers (median age 62; 80% with epithelial ovarian most cancers; 59% stage III) with excessive ranges of FRα expression. That they had a median of three prior strains of remedy, with 51% having three prior strains and 48% one or two prior strains. All sufferers obtained prior bevacizumab, whereas 48% of sufferers obtained a previous PARP inhibitor.

Sufferers obtained IV mirvetuximab at 6 mg/kg, utilizing adjusted ideally suited physique weight, as soon as each 3 weeks till illness development or insupportable unwanted effects.

Confirmed goal responses by investigators have been seen in 34 of 105 evaluable sufferers, together with 5 full responses (CRs). The ORR by blinded unbiased central evaluate (BICR) was 31.6% (95% CI 22.4%-41.9%), together with 5 CRs.

“The response fee is sort of triple the benchmark set in prior research of much less closely pretreated platinum-resistant ovarian most cancers populations,” Matulonis reported.

ORRs by investigator have been constant no matter variety of prior strains of therapies or prior PARP inhibitor:

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

The median length of response was 6.9 months (95% CI 5.6-8.1) by investigators as of the March 3, 2022 information cut-off. Period of response by prior remedy was 5.9 months for sufferers with one to 2 strains of prior remedy, 7.0 months for sufferers with three strains of remedy, 5.7 months for sufferers with prior PARP inhibitor publicity, and 5.9 months for these with out prior PARP inhibitor publicity.

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 sufferers, dose delays in 32% of sufferers, and discontinuations in 7% of sufferers. One loss of life on account of respiratory failure was recorded as probably associated to mirvetuximab, however post-mortem evaluate confirmed the affected person had lung metastases, bronchopneumonia, and no proof of drug response, based on Matulonis.

  • author['full_name']

    Mike Bassett is a employees author specializing in oncology and hematology. He’s based mostly in Massachusetts.


The examine was funded by ImmunoGen. Some co-authors are firm staff.

Matulonis disclosed relationships with Novartis, AstraZeneca, Merck, GlaxoSmithKline, Trillium, Blueprint Medicines, Agenus, ImmunoGen, NextCure, Ovarian Most cancers Analysis Alliance, Rivkin Basis, Clearity, Symphogen, Alkermes, and Advaxis.

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