Impressive efficacy data and consistent safety data continue to be seen with mirvetuximab soravtansine for the treatment of patients with platinum-resistant ovarian cancer, according to data from the confirmatory MIRASOL trial.
Mirvetuximab sorvtansine-gynx (Elahere) demonstrated statistically significant improvements in response rates and survival vs chemotherapy of physician’s choice in patients with folate receptor alpha (FRα)-positive platinum-resistant ovarian cancer who have received 1-3 previous lines of therapy, according to positive top-line data from the phase 3 confirmatory MIRASOL trial (GOG 3045/ENGOT OV-55; NCT04209855).1
There were 204 overall survival (OS) events as of the cutoff date, and the median OS was 16.46 months among patients in the mirvetuximab soravtansine arm vs 12.75 months in the chemotherapy arm (HR, 0.67; P =.0046), representing a 33% reduction in the risk of death between the experimental and chemotherapy arms.
A statistically significant and clinically meaningful improvement in progression-free survival (PFS) was also seen with mirvetuximab soravtansine with a hazard ratio of 0.65 (P < .0001), which represents a 35% reduction in the risk of tumor progression or death among patients treated with mirvetuximab soravtansine vs chemotherapy. The median PFS with mirvetuximab soravtansine was 5.62 months and 3.98 months with chemotherapy.
Further, the overall response rate (ORR) with mirvetuximab soravtansine was 42.3% and included 12 complete responses (CRs). In the chemotherapy arm, the ORR was 15.9%, and no CRs were observed.
"The data from MIRASOL confirms what we saw with the SORAYA [NCT04296890] results that led to accelerated approval of mirvetuximab in folate receptor alpha positive recurrent platinum resistant ovarian cancer. MIRASOL showed that mirvetuximab in folate receptor alpha positive recurrent platinum resistant ovarian cancer had statistically significant better overall survival, progression-free survival and response rates compared to [investigator's] choice chemotherapy. No new toxicities were observed with mirvetuximab. I cannot think of another trial where a new agent has showed an improvement in overall survival compared to traditional non-platinum chemotherapy for platinum resistant ovarian cancer," Ursula A. Matulonis, MD, chief of the Division of Gynecologic Oncology at the Dana-Farber Cancer Institute, told Targeted OncologyTM.
"I believe the data from the confirmatory MIRASOL trial are practice-changing. They demonstrate [mirvetuximab soravtansine] superiority to chemotherapy based on all efficacy endpoints, in particular overall survival, and build on the clinical benefit of [mirvetuximab soravtansine] previously reported in the SORAYA trial [NCT04296890]," said Kathleen Moore, associate director of clinical research and director of the Oklahoma TSET/Sarah Cannon phase I program, professor of the section of gynecologic oncology at The University of Oklahoma and MIRASOL principal investigator, in the press release.
The FDA previously granted mirvetuximab soravtansine accelerated approval in November 2022 for the treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received 1-3 prior systemic treatment regimens. This approval was based on positive ORR and duration of response data from the pivotal SORAYA trial.
"Last year's accelerated approval of [mirvetuximab soravtansine] was a paradigm-shifting development in the treatment landscape for this disease and I am confident that, with the MIRASOL data, [mirvetuximab soravtansine] has the potential to become the new standard of care for patients with FRα-positive, platinum-resistant ovarian cancer. FRα status is a 'must know' for all ovarian cancer patients and, for those with platinum-resistant disease who test positive, I believe [mirvetuximab soravtansine] should be their first treatment option," added Moore in the press release.
The randomized phase 3 MIRASOL trial assessed the efficacy and safety of mirvetuximab soravtansine vs investigator's choice of single-agent chemotherapy, including either weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan.
Patients with platinum-resistant ovarian cancer whose tumors express high levels of FRα, using the Ventana FOLR1 Assay, and who have been treated with up to 3 prior regimens were eligible for enrollment in the trial.2 Patients must have been aged 18 years and older, have progressed radiographically on or after their most recent line of therapy, have at least one lesion that meets the definition of measurable disease by RECIST v1.1, have an ECOG performance status of 0-1, have stabilized or recovered from all prior therapy-related toxicities, and have adequate hematologic, liver, and kidney functions.
Investigators evaluated the primary end point of PFS by investigator assessment and key secondary end points were ORR and OS.
A total of 453 patients were enrolled in the MIRASOL trial with 1 prior line of therapy being seen in 14% of patients, 2 prior lines in 39%, and 3 prior lines in 47%. A total of 62% of patients received prior bevacizumab and 55% received a prior PARP inhibitor.1
According to findings, the PFS and ORR results by blinded independent central review were consistent with investigator assessment. The median follow-up time for OS as of the data cutoff date on March 6, 2023, was 13.1 months among patients treated with mirvetuximab soravtansine, and 14% of patients treated with the agent remained on study drug compared with 3% on the investigator’s choice of chemotherapy arm.
The safety profile of mirvetuximab soravtansine also continued to show mostly low-grade ocular and gastrointestinal events. No new safety signals were identified with the agent.
When compared with investigators' choice of chemotherapy, treatment with mirvetuximab soravtansine led to lower rates of grade 3 or greater treatment-emergent adverse events (TEAEs; 42% v 54%) and serious adverse events (24% v 33%). Additionally, patients treated with the mirvetuximab soravtansine had less TEAEs which led to the discontinuation of study drug (9% v 16%).
Treatment with mirvetuximab soravtansine is the first of its kind to lead to an OS advantage among patients with platinum-resistant ovarian cancer. Based on these data, a supplemental biologics license application is expected to be submitted to the FDA in the United States, as well as a marketing authorization application in Europe for the conversion to a regular approval of the agent.
"These results are very impressive and confirm mirvetuximab’s role in the treatment of patients with FRα-positive platinum-resistant ovarian cancer. This is a very important and game changing new therapy for our patients. Patients with ovarian cancer should have FRα testing done at initial diagnosis. Mirvetuximab is now being studied in patients with platinum-sensitive recurrent ovarian cancer, as well as newly diagnosed patients. Additionally, we are studying mirvetuximab as a single agent, as well as in a combination with other agents in other gynecologic cancers such as endometrial serous cancer," added Matulonis.