Mirvetuximab Soravtansine in Combination with Carboplatin and Bevacizumab in Recurrent Ovarian Cancer

Conference Correspondent  - ESMO 2020

Mirvetuximab soravtansine is a folate receptor alpha (FRα)-targeting antibody-drug conjugate made up of maytansinoid DM4, a potent tubulin-targeting agent, and a cleavable linker. The FORWARD II investigation is a phase 1b study evaluating maintenance therapy with the combination of mirvetuximab soravtansine, carboplatin, and bevacizumab in patients with recurrent platinum-sensitive ovarian cancer. Eligibility included no progression within 6 months of the last dose of platinum-containing therapy, FRα positivity (≥50% of cells with ≥2+ staining intensity), at least 1 lesion that met the RECIST 1.1 criteria for measurable disease, and previous treatment with 1 to 2 prior lines of treatment.

The study enrolled 41 patients who received mirvetuximab soravtansine (6 mg/kg [adjusted ideal body weight]) + carboplatin (AUC 5) + bevacizumab (15 mg/kg) administered on day 1 of a 3-week cycle, which was followed by maintenance therapy with mirvetuximab soravtansine and bevacizumab. The median number of cycles was 6 cycles of carboplatin, 12 cycles of mirvetuximab soravtansine, and 13 cycles of bevacizumab.

The median age of enrolled patients was 63 years. Approximately 56% of enrolled patients had an Eastern Cooperative Oncology Group score of 0, and 44% had a score of 1. Nearly 75% of patients had undergone 1 prior line of therapy, and approximately 25% had received 2 lines of prior treatment. The study included 17 patients with previous poly (ADP-ribose) polymerase (PARP) inhibitor exposure and 10 with previous exposure to bevacizumab. The platinum-free treatment interval was ≤12 months in 54% of patients. Tumor FRα expression was high in 49% of patients and medium in the remainder of patients.

The confirmed overall response rate was 83% (95% confidence interval [CI], 68-93) in the overall patient population, 80% (95% CI, 56-94) in the high tumor FRα expression group, and 86% (95% CI, 64-97) in the medium tumor FRα expression group. The median duration of response was 10.9 months (95% CI, 7.7-13.6) in the overall patient population, and 9.9 months (95% CI, 7.5-12.3) and 13.3 months (95% CI, 6.7-15.2) in patients whose tumors had high or medium FRα expression, respectively. Progression-free survival was 12.8 months (95% CI, 9.1-14.6) in the overall patient population, 12.4 months (95% CI, 9.0-14.6) in patients with high FRα tumor expression, and 12.9 months (95% CI, 8.1-16.2) in the medium FRα expression subgroup. The researchers noted confirmed tumor responses in 34 patients, which included 10 complete responses and 24 partial responses.

The most common treatment-emergent–related adverse events (all grades) were diarrhea (83%), nausea and fatigue (76%), thrombocytopenia (71%), blurred vision (68%), and peripheral neuropathy (56%). Grade 3 adverse events occurring in at least 10% of patients included thrombocytopenia (42%), neutropenia (32%), anemia (12%), and hypertension and diarrhea (10%). Approximately 10% of patients experienced grade 4 neutropenia and thrombocytopenia. Treatment discontinuation of at least 1 drug due to adverse events occurred in 54% of patients; 37% of patients discontinued carboplatin due to grade 2/3 thrombocytopenia, 32% of patients discontinued mirvetuximab soravtansine mainly due to grade 2/3 thrombocytopenia or grade 2 blurred vision, and bevacizumab was discontinued by 5% of patients due to a grade 3 colonic fistula and grade 2 thrombocytopenia.

The study results demonstrated that mirvetuximab soravtansine combined with carboplatin and bevacizumab is a highly active treatment regimen with favorable tolerability in patients with recurrent, platinum-sensitive ovarian cancer.

Reference

Abstract and Poster 833P. ESMO 2020. September 19-12, 2020. Mirvetuximab soravtansine (MIRV), a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with carboplatin (CARBO) and bevacizumab (BEV): final results from a study in patients (pts) with recurrent platinum sensitive ovarian cancer.

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Last modified: September 22, 2020