Mirvetuximab Soravtansine Effective in Patients With FRα+, Platinum-Sensitive Ovarian Cancer

New phase 2 PICCOLO trial data (NCT05041257) presented last month at the European Society for Medical Oncology (ESMO) Congress 2024 demonstrated the efficacy and tolerability of mirvetuximab soravtansine (Elahere; AbbVie) in heavily pretreated patients with folate receptor alpha-positive (FRα+), platinum-sensitive ovarian cancer (PSOC), a historically challenging population to treat.¹

Mirvetuximab soravtansine (Elahere; AbbVie) is effective and tolerable in heavily pre-treated patients with folate receptor alpha-positive (FRα+), platinum-sensitive ovarian cancer (PSOC). | Image Credit: Dr_Microbe - stock.adobe.com

Efficacy of Mirvetuximab Soravtansine for Patients With FRα+, PROC

In November 2022, mirvetuximab soravtansine, an FRα-directed antibody and microtubule inhibitor conjugate, was granted accelerated FDA approval to treat patients with FRα+, platinum-resistant ovarian cancer (PROC) based on results from the SORAYA study (Study 0417).² Full FDA approval was granted earlier this year based on findings from the phase 3 MIRASOL trial (NCT04209855).

In the MIRASOL trial, 453 patients with FRα+ PROC received either mirvetuximab soravtansine (n = 227) or the investigator’s choice of single-agent chemotherapy (n = 226). Progression-free survival (PFS), the trial’s primary endpoint, was longer in the mirvetuximab soravtansine cohort (5.62 months; 95% CI, 4.34-5.95) than in the chemotherapy cohort (3.98 months; 95% CI, 2.86-4.47).

Also, those in the mirvetuximab soravtansine cohort experienced significantly longer median overall survival (OS) at 16.46 months (95% CI, 14.46-24.57) compared with 12.75 months (95% CI, 10.91-14.36) among those in the chemotherapy cohort (HR, 0.67; 95% CI, 0.50-0.89; P = .005).

Similarly the investigator-assessed objective response rate (ORR) was significantly higher in the mirvetuximab soravtansine group (42.3%; 95% CI, 35.8-49.0) vs the chemotherapy group (15.9%; 95% CI, 11.4-21.4), which equates to an OR of 3.81 (95% CI, 2.44-5.94; P < .001).

Of the patients who responded to mirvetuximab soravtansine, 5.3% (n = 12) experienced a complete response and 37% had a partial response. However, no patients in the chemotherapy group experienced a complete response, but 15.9% (n = 36) experienced a partial response.

"As the first treatment to show a statistically significant overall survival benefit in patients with PROC, [mirvetuximab soravtansine] provides an effective new option for patients with FRα+ tumors," Kathleen Moore, associate director of clinical research at the Stephenson Cancer Center at The University of Oklahoma and MIRASOL principal investigator, said in a press release.³ "These patients previously had very limited options and [mirvetuximab soravtansine] changes that."

Efficacy, Safety of Mirvetuximab Soravtansine in Heavily Pre-Treated Patients With FRα+, PSOC

The phase 2 PICCOLO trial built upon the MIRASOL trial’s findings by evaluating the efficacy and safety of mirvetuximab soravtansine in heavily pre-treated patients with FRα+, PSOC.¹ Its primary endpoint was the confirmed ORR, and the key secondary endpoint was the duration of response (DOR). Additional secondary endpoints included OS, PFS, and safety.

Eligible participants included those with PSOC with high FRα expression, meaning 75% or higher of their cells had moderate staining intensity, as determined by the PS2+ scoring method. Also, eligible patients had at least 2 prior lines of platinum-containing therapy or a documented platinum allergy.

Seventy-nine patients were enrolled before the data cutoff of January 17, 2024. Of the study population, 98.8% had 2 or more prior lines of therapy. More specifically, 97.5% were previously treated with taxanes, 81% with poly (ADP-ribose) polymerase (PARP) inhibitors, and 64.6% with bevacizumab.

During the trial, patients received mirvetuximab soravtansine at a dose of 6 mg/kg based on their adjusted ideal body weight on day 1 of a 21-day cycle, continuing until disease progression or unacceptable toxicity. Among the 79 patients, the ORR was 51.9% (95% CI, 40.4-63.3), including 6 complete and 35 partial responses.

Additionally, the median DOR was 8.3 months (95% CI, 5.5-10.8), and the median PFS (mPFS) was 6.9 months (95% CI, 5.9-9.6). Conversely, the OS was not mature at the data cutoff.

The most common treatment-emergent adverse events (TEAEs) were blurred vision (63%), nausea (37%), dry eye (37%), keratopathy (33%), and diarrhea (30%). These TEAEs led to dose delays, reduction, and discontinuations in 61%, 42%, and 16% of patients, respectively.

Despite these TEAEs, primary investigator Angeles Alvarez Secord, MD, MHSc, professor of obstetrics and gynecology at Duke Cancer Institute, discussed these encouraging trial results with The American Journal of Managed Care^® (AJMC^®).⁴

She noted that heavily pretreated platinum-sensitive patients may not qualify for repeat platinum therapy due to hypersensitivity or bone marrow suppression, highlighting how mirvetuximab soravtansine can address this treatment gap.

“This is a really exciting opportunity to be able to give those patients a drug that has greater efficacy compared with single-agent paclitaxel, liposomal doxorubicin, or gemcitabine, which would be your other options—so a really reasonable, highly effective therapy that is also tolerable,” Secord told AJMC. “Overall, there is a strong, urgent, patient-driven need to identify novel therapies that have really favorable side effect profiles for these patients who have received so much prior therapy.”

References

1. Secord AA. Mirvetuximabsoravtansine (MIRV) in recurrent platinum-sensitive ovarian cancer (PSOC) with high folate receptor-alpha (FRα) expression: Results from the PICCOLO trial. Presented at: European Society of Medical Oncology Congress 2024; September 13-17, 2024; Barcelona, Spain. Abstract 718MO.
2. McNulty R. Mirvetuximab soravtansine-gynx granted full FDA approval for FRα+ platinum-resistant ovarian cancer. AJMC. March 22, 2024. Accessed October 15, 2024. https://www.ajmc.com/view/mirvetuximab-soravtansine-gynx-granted-full-fda-approval-for-fr-platinum-resistant-ovarian-cancer
3. U.S. Food and Drug Administration (FDA) grants full approval for Elahere (mirvetuximab soravtansine-gynx) for certain ovarian cancer patients. News release. AbbVie. March 22, 2024. Accessed October 15, 2024. https://www.prnewswire.com/news-releases/us-food-and-drug-administration-fda-grants-full-approval-for-elahere-mirvetuximab-soravtansine-gynx-for-certain-ovarian-cancer-patients-302097362.html
4. McNulty R. Dr Angeles Alvarez Secord on “exciting” responses with mirvetuximabsoravtansine in platinum-sensitive ovarian cancer. AJMC. September 15, 2024. Accessed October 15, 2024. https://www.ajmc.com/view/dr-angeles-alvarez-secord-on-exciting-responses-with-mirvetuximab-soravtansine-in-platinum-sensitive-ovarian-cancer