FDA Grants Full Approval to Mirvetuximab Soravtansine for FRα+ Platinum-Resistant Ovarian Cancer

FDA

The FDA has granted regular approval to mirvetuximab soravtansine-gynx (Elahere) for adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have previously received one to three systemic treatment regimens.^1,2

The regulatory decision is supported by data from the phase 3 MIRASOL study (Study 0416; NCT04209855) in which the antibody-drug conjugate (ADC; n = 227) improved median overall survival (OS) vs investigator's choice of chemotherapy (n = 226), at 16.5 months (95% CI, 14.5-24.6) vs 12.7 months (95% CI, 10.9-14.4), respectively (HR, 0.67; 95% CI, 0.50-0.88; P = .0046).

Mirvetuximab soravtansine also improved progression-free survival (PFS) vs chemotherapy, at a median of 5.6 months (95% CI, 4.3-5.9) vs 4.0 months (95% CI, 2.9-4.5), respectively (HR, 0.65; 95% CI, 0.52-0.81; P < .0001). Moreover, the ADC elicited an objective response rate (ORR) of 42% (95% CI, 36%-49%) vs 16% (95% CI, 12%-22%) with chemotherapy (P < .0001). Of those who responded to treatment with the ADC, 5% achieved a complete response and 37% experienced a partial response.

About MIRASOL: Eligibility, Treatment, Objectives

The multicenter, open-label, active-controlled, randomized trial enrolled patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer (n = 453) who were allowed to have previously received up to three lines of systemic therapy. If they had corneal disorders, ocular conditions that need treatment, peripheral neuropathy greater than grade 1 in severity, or noninfectious interstitial lung disease, they were excluded.

Study participants were randomly assigned 1:1 to receive 6 mg/kg of intravenous mirvetuximab soravtansine, based on adjusted ideal body weight, every 3 weeks vs investigator's choice of chemotherapy, which could have included paclitaxel, pegylated liposomal doxorubicin (PLD), or topotecan.

Treatment continued until progressive disease or intolerable toxicity. Key stratification factors included number of prior lines of treatment (1 vs 2 vs 3) and chemotherapy agent selected before randomization (paclitaxel vs PLD vs topotecan).

Investigator-assessed PFS and confirmed ORR by RECIST v1.1 criteria and OS.

Study Population: Baseline Characteristics

The median patient age was 63 years (range, 29-88). More than half of patients were White (66%). Regarding ECOG performance status, 55% had a status of 0, and 44% had a status of 1. In terms of prior systemic treatment, 14% had 1 prior line, 39% had 2 prior lines, and 47% had 3 prior lines. Moreover, 37% of patients previously received systemic therapy for platinum-resistant disease. More than half of patients previously received bevacizumab (Avastin) or a PARP inhibitor (55%).

Safety

Regarding safety, dose delays and reductions of mirvetuximab soravtansine were required due to adverse effects (AEs) for 54% and 34% of patients, respectively. AEs led to permanent treatment discontinuation of the ADC for 9% of patients. The most common toxicities that led to discontinuation included pneumonitis (2%), blurred vision (1%), and peripheral neuropathy (1%). Serious AEs occurred in 24% of patients.

The most common AEs experienced by 10% or more patients who received mirvetuximab soravtansine (n = 218) included abdominal pain (all grade, 34%; grade 3/4, 3%), diarrhea (29%; 1%), constipation (27%; 0%), nausea (27%; 2%), vomiting (18%; 3%), blurred vision (45%; 9%), kertopathy (37%; 11%), dry eye (29%; 3%), photophobia (18%; 0.5%, cataract (16%; 3%), fatigue (47%; 3%), peripheral neuropathy (37%; 4%), headache (14%; 0%), musculoskeletal pain (31%; 1%), reduced appetite (18%; 1%), and pneumonitis (10%; 0.5%).

Toxicities noted to be clinically relevant and were experienced by fewer than 10% of patients who received the ADC in the study included infusion-related reactions or hypersensitivity (8%).

The most common laboratory abnormalities experienced by at least 10% of patients who received mirvetuximab soravtansine on the trial included increases in aspartate aminotransferase (all grade, 57%; grade 3/4, 0%), alanine aminotransferase (38%; 1%), alkaline phosphatase (30%; 1%), calcium (12%; 0%), and creatinine (10%; 0%); and decreases in albumin (21%; 1%), magnesium (21%; 1%), sodium (16%; 0%), potassium (15%; 1%), bicarbonate (11%; 0%), lymphocytes (27%; 3%), leukocytes (23%; 1%), neutrophils (22%; 1%), hemoglobin (18%; 1%), and platelet counts (17%; 1%).

References

1. FDA approves mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. FDA. Accessed March 22, 2024. Accessed March 22, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mirvetuximab-soravtansine-gynx-fra-positive-platinum-resistant-epithelial-ovarian
2. Elahere. Prescribing information. ImmunoGen, Inc.; 2024. Accessed March 22, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761310Origs005lbl.pdf