Phase 2 Study of Mirvetuximab in Ovarian Cancer Meets Primary End Point

Female reproductive organs, artistic design, transparent flower at the background: © reineg - stock.adobe.com

When given as a monotherapy, mirvetuximab soravtansine (Elahere) led to an objective response rate (ORR) of 51.9% (95% CI, 40.4%-63.3%) in heavily pretreated patients with folate receptor alpha (FRα)-positive, platinum-sensitive ovarian cancer, meeting the primary end point of the phase 2 PICCOLO trial (NCT05041257).¹

In addition to these positive topline data from the phase 2 study, the key secondary end point of median duration of response (DOR) was 8.25 months, and no new safety concerns were identified, showing the safety profile of the therapy to be consistent with what has been shown in prior studies.

Full data from PICCOLO 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," said Angeles Alvarez Secord, MD, MHSc, from the Duke Cancer Institute, in a press release. "The PICCOLO data further support the potential of mirvetuximab soravtansine for platinum-sensitive ovarian cancer patients."

Mirvetuximab soravtansine is a first-in-class antibody-drug conjugate (ADC) composed of an FRα-binding antibody, cleavable linker, and a tubulin inhibitor. In November 2022, the agent was granted accelerated approval from the FDA for FRα-high platinum-resistant ovarian cancer, and in March 2024, the ADC was granted full approval for the treatment of platinum-resistant ovarian cancer with high expression that has received 1 to 3 prior lines of treatment.

In the single-arm, phase 2 PICCOLO trial, investigators are evaluating the safety and efficacy of mirvetuximab soravtansine given alone in patients with FRα-high platinum-sensitive ovarian cancer. A total of 79 patients have been enrolled in the study.²

Patients are required to have been treated with 2 or more previous lines of platinum-containing therapy or have a documented platinum allergy. Additional inclusion criteria require patients to be 18 years or older with a confirmed diagnosis of high-grade serous epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer and an ECOG performance status of 0 or 1. Patients must have platinum-sensitive disease, have progressed radiographically on or after their most recent line of anticancer therapy, have at least 1 lesion that meets the definition of measurable disease by RECIST v1.1, and be willing to provide an archival tumor tissue block or slides or undergo procedure to obtain a new biopsy using a low-risk, medically routine procedure for immunohistochemistry confirmation of FRα positivity.

Further, patients must have a tumor that is positive for FRα expression as defined by the Ventana FOLR1 Assay, have stabilized or recovered from all previous therapy-related toxicities (excluding alopecia), have completed any major surgery at least 4 weeks prior to the first dose of the study drug, have recovered or stabilized from the adverse effects of prior surgery prior to being treated with the first dose, and have adequate hematologic, liver, and kidney functions.

In addition to the primary end point of ORR and key secondary end point of DOR, other secondary end points include assessing treatment-emergent adverse effects, cancer antigen-125, progression-free survival, overall survival, and sensitivity analysis.

In addition to the PICCOLO study, mirvetuximab soravtansine is also being evaluated in this patient population in the phase 3 GLORIOSA trial (NCT05445778). Here, it is being tested in combination with bevacizumab (Avastin) compared with bevacizumab alone in maintenance after second-line platinum-doublet therapy.

REFERENCES:
1. AbbVie announces positive topline results from phase 2 PICCOLO 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://tinyurl.com/4kmav2wz
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://clinicaltrials.gov/study/NCT05041257