Mirvetuximab Soravtansine Meets Primary End Point of PICCOLO Trial in FRα-High, Platinum-Sensitive Ovarian Cancer

Mirvetuximab soravtansine-gynx (Elahere) produced an objective response rate (ORR) of 51.9% (95% CI, 40.4%-63.3%) and a median duration of response was 8.25 months in heavily pretreated patients with folate receptor–alpha (FRα)-positive, platinum-sensitive ovarian cancer, meeting the primary and secondary end points of the phase 3 PICCOLO trial (NCT05041257).^1,2

The safety profile of the antibody-drug conjugate (ADC) was in line with findings from past trials, and no new signals were documented. Complete data from the trial will be presented at an upcoming medical meeting.

“Significant unmet needs remain for patients with platinum-sensitive disease, as each subsequent line of therapy in this setting is associated with decreased efficacy and tolerability, which reinforces the need for treatment alternatives for these patients,” Angeles Alvarez Secord, MD, MHSc, of Duke Cancer Institute, stated in a news release. “The PICCOLO data further support the potential of mirvetuximab soravtansine for platinum-sensitive ovarian cancer patients.”

Standard-of-care treatment does not exist for patients with heavily pretreated platinum-sensitive ovarian cancer or those who are ineligible for platinum-based therapy, especially following progression on a PARP inhibitor.

In March 2024, the FDA granted full approval to mirvetuximab soravtansine for the treatment of patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received no more than 3 prior lines of therapy. The decision was based one efficacy and safety findings from the confirmatory phase 3 MIRASOL trial(NCT04209855), which demonstrated an improvement in progression-free survival (PFS) and overall survival (OS) with the ADC vs investigator’s choice of chemotherapy in this population.³

PICCOLO is a single-arm, phase 2 trial evaluating the efficacy and safety of mirvetuximab soravtansine as a single agent in patients with FRα-high, platinum-sensitive ovarian cancer following at least 2 prior lines of platinum-containing therapy or documentation of a platinum allergy.¹ The primary end point is ORR, and the key secondary end point is DOR. Treatment-emergent adverse effects, CA-125 level, PFS, and OS will also be evaluated as secondary end points.

To be eligible for enrollment, patients must be at least 18 years of age and have a confirmed diagnosis of high-grade serous epithelial ovarian cancer, primary peritoneal, or fallopian tube cancer. Additional criteria included platinum-sensitive disease defined as radiographic progression greater than 6 months from the last dose of the most recent platinum therapy; at least 1 measurable lesion per RECIST 1.1 criteria; FRα positivity as defined by the Ventana FOLR1 assay; and an ECOG performance status of 0 or 1.2

Eligible patients will receive mirvetuximab soravtansine at 6.0 mg/kg adjusted by ideal body weight.¹

The PICCOLO study was designed to statistically rule out an ORR of 28% or lower, as excluded by the lower bound of the confidence interval, a response rate that has been achieved with non-platinum, single-agent chemotherapy in patients with platinum-sensitive disease.

Mirvetuximab soravtansine is also being evaluated in patients with platinum-sensitive ovarian cancer in the phase 3 GLORIOSA trial (NCT05445778), in which patients will be randomly assigned to receive maintenance therapy with either the ADC in combination with bevacizumab (Avastin) or bevacizumab alone after second-line platinum-doublet therapy.

References

1. AbbVie announces positive topline results from phase 2 PICCOLO trial evaluating mirvetuximab soravtansine (ELAHERE) for high folate receptor-alpha (FRα) expressing platinum-sensitive ovarian cancer. News release. AbbVie. June 6, 2024. Accessed June 6, 2024. https://news.abbvie.com/2024-06-06-AbbVie-Announces-Positive-Topline-Results-from-Phase-2-PICCOLO-Trial-Evaluating-Mirvetuximab-Soravtansine-ELAHERE-R-for-High-Folate-Receptor-Alpha-FR-Expressing-Platinum-Sensitive-Ovarian-Cancer
2. Mirvetuximab soravtansine monotherapy in platinum-sensitive epithelial, peritoneal, and fallopian tube cancers (PICCOLO). ClinicalTrials.gov. Updated April 22, 2024. Accessed June 6, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05041257
3. US Food and Drug Administration (FDA) grants full approval for ELAHERE (mirvetuximab soravtansine-gynx) for certain ovarian cancer patients. News release. March 22, 2024. Accessed June 6, 2024. https://news.abbvie.com/2024-03-22-U-S-Food-and-Drug-Administration-FDA-Grants-Full-Approval-for-ELAHERE-R-mirvetuximab-soravtansine-gynx-for-Certain-Ovarian-Cancer-Patients