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Efficacy and Safety of Mirvetuximab Soravtansine in Patients with Platinum-Resistant Ovarian Cancer with High Folate Receptor Alpha Expression: Results from the SORAYA Study (LBA 4)

2022; Elsevier BV; Volume: 166; Linguagem: Inglês

10.1016/s0090-8258(22)01297-5

1095-6859

Ursula A. Matulonis, Domenica Lorusso, Ana Oaknin, Sandro Pignata, Hannelore Denys, Nicoletta Colombo, Toon Van Gorp, Jason Konner, Margarita Romeo, Philipp Harter, Conleth G. Murphy, Jiuzhou Wang, Elizabeth Noble, Brooke Esteves, Michael Method, Robert E. Coleman,

Renal cell carcinoma treatment

Objectives: Available single agent chemotherapies for platinum-resistant ovarian cancer have limited clinical activity and considerable toxicity. Mirvetuximab soravtansine (MIRV) is an antibody drug conjugate (ADC) comprising a FRα-binding antibody, cleavable linker, and maytansinoid DM4, a potent tubulin-targeting agent. SORAYA is a global single arm phase 3 study evaluating MIRV in adult patients (pts) with FRα high platinum-resistant high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancers (PROC). Methods: SORAYA enrolled PROC pts with high levels of FRα expression by immunohistochemistry (Roche FOLR1 Assay ≥ 75% of cells with PS2+ staining intensity) who had received 1-3 prior therapies, including required prior bevacizumab. Pts received intravenous MIRV at 6 mg/kg, adjusted ideal body weight, on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was confirmed objective response rate (ORR) per RECIST v1.1 by investigator (INV); the key secondary endpoint was duration of response (DOR); additional secondary endpoints included safety and tolerability. ORR and DOR by blinded independent central review (BICR) were sensitivity analyses. Results: 106 pts were enrolled; 51% had 3 prior lines; 48% had 1 to 2 prior lines of therapy. All pts received prior bevacizumab; 48% received a prior PARP inhibitor (PARPi). Median follow-up time was 8.5 months at the data cutoff on November 16, 2021. Objective responses by INV were seen in 34 of 105 efficacy evaluable pts for an ORR of 32.4% (95% confidence interval [CI]: 23.6%, 42.2%), including five complete responses (CRs); ORR by BICR was 31.6% (95% CI: 22.4%, 41.9%), including five CRs. The median DOR was 5.9 months (95% CI: 5.6, 7.7). With 15 responders remaining on MIRV at the time of the data cutoff, the DOR continues to evolve. In pts with 1-2 priors, the ORR by INV was 35.3% (95% CI: 22.4%, 49.9) and in pts with 3 priors, it was 30.2% (95% CI: 18.3%, 44.3). In pts with prior PARPi, the ORR by INV was 38.0% (95% CI: 24.7, 52.8) and in those without prior PARPi, it was 27.5% (95% CI: 15.9, 41.7). See table. The most common treatment-related adverse events (all grade, grade 3+) included blurred vision (41%, 6%), keratopathy (36%, 9%), and nausea (29%, 0%). Treatment-related adverse events led to dose reductions in 19%, dose delays in 32%, and discontinuations in 7% of pts; only one patient discontinued treatment due to an ocular event. Objectives: Available single agent chemotherapies for platinum-resistant ovarian cancer have limited clinical activity and considerable toxicity. Mirvetuximab soravtansine (MIRV) is an antibody drug conjugate (ADC) comprising a FRα-binding antibody, cleavable linker, and maytansinoid DM4, a potent tubulin-targeting agent. SORAYA is a global single arm phase 3 study evaluating MIRV in adult patients (pts) with FRα high platinum-resistant high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancers (PROC). Methods: SORAYA enrolled PROC pts with high levels of FRα expression by immunohistochemistry (Roche FOLR1 Assay ≥ 75% of cells with PS2+ staining intensity) who had received 1-3 prior therapies, including required prior bevacizumab. Pts received intravenous MIRV at 6 mg/kg, adjusted ideal body weight, on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was confirmed objective response rate (ORR) per RECIST v1.1 by investigator (INV); the key secondary endpoint was duration of response (DOR); additional secondary endpoints included safety and tolerability. ORR and DOR by blinded independent central review (BICR) were sensitivity analyses. Results: 106 pts were enrolled; 51% had 3 prior lines; 48% had 1 to 2 prior lines of therapy. All pts received prior bevacizumab; 48% received a prior PARP inhibitor (PARPi). Median follow-up time was 8.5 months at the data cutoff on November 16, 2021. Objective responses by INV were seen in 34 of 105 efficacy evaluable pts for an ORR of 32.4% (95% confidence interval [CI]: 23.6%, 42.2%), including five complete responses (CRs); ORR by BICR was 31.6% (95% CI: 22.4%, 41.9%), including five CRs. The median DOR was 5.9 months (95% CI: 5.6, 7.7). With 15 responders remaining on MIRV at the time of the data cutoff, the DOR continues to evolve. In pts with 1-2 priors, the ORR by INV was 35.3% (95% CI: 22.4%, 49.9) and in pts with 3 priors, it was 30.2% (95% CI: 18.3%, 44.3). In pts with prior PARPi, the ORR by INV was 38.0% (95% CI: 24.7, 52.8) and in those without prior PARPi, it was 27.5% (95% CI: 15.9, 41.7). See table. The most common treatment-related adverse events (all grade, grade 3+) included blurred vision (41%, 6%), keratopathy (36%, 9%), and nausea (29%, 0%). Treatment-related adverse events led to dose reductions in 19%, dose delays in 32%, and discontinuations in 7% of pts; only one patient discontinued treatment due to an ocular event.