Results of the phase 3 MIRASOL study evaluating mirvetuximab soravtansine for platinum-resistant ovarian cancer will be announced at an upcoming meeting.
Mirvetuximab soravtansine-gynx (Elahere) has shown improvement in progression-free survival (PFS), objective response rates (ORR), and overall survival (OS), according to 2 subset analyses of the phase 3 MIRASOL study (NCT04209855), which is evaluating mirvetuximab soravtansine compared to chemotherapy for the treatment of patients with folate receptor alpha (FRα)-positive platinum-resistant ovarian cancer (PROC).1
“Consistent with the strong topline MIRASOL data where superiority was seen across all efficacy endpoints, these subset analyses show that the improvements in progression-free survival, objective response rates, and overall survival demonstrated in the overall study population are also observed regardless of the number of prior lines of therapy,” said Toon Van Gorp, MD, professor of gynecological oncology at the University of Leuven, in a press release.
“Importantly, the benefit seen with Elahere in patients treated with a prior PARP inhibitor is particularly encouraging, as it has been shown that PARP inhibitors have a potential negative impact on the efficacy of subsequent chemotherapies. These new data being presented at ESGO, including a consistent safety and tolerability profile, provide valuable insights for physicians into Elahere’s broad and meaningful benefit compared to chemotherapy and further position Elahere to become the new standard of care for patients with FRα-positive PROC,” Van Gorp added.
The FDA granted approval to mirvetuximab soravtansine in November 2022 for the treatment of patients with FRα-positive PROC who had received 1 to 3 previous lines of treatment (PLOT). The SORAYA trial (NCT04296890) reported an ORR of 31.7% and a median duration of response of 6.9 months.2
The MIRASOL study included 453 patients with PROC whose tumors expressed high levels of FRα. Fourteen percent of patients had 1 prior line of therapy, 40% had 2 prior lines, and 46% had 3 prior lines. Researchers compared mirvetuximab soravtansine to investigator’s choice (IC) of chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). Paclitaxel was the most common IC of chemotherapy, with 41% of patients having received it. Thirty-six percent of patients received pegylated liposomal doxorubicin, and 23% of patients received topotecan. Sixty-two percent of patients previously received bevacizumab (Avastin), and 55% received a PARPi.1,3
In patients who were previously administered a PARPi (n=251), PFS hazard ratio (HR) was 0.58 (95% CI, 0.43, 0.78; P=.0002).ORR in those who received mirvetuximab soravtansine was 45% (95% CI, 36%-54%), including 7 complete responses (CR), compared to 17% (95% CI, 11%-25%). The HR for OS was 0.48 (95% CI, 0.33-0.71; P=.0002).1
In patients who were not previously administered aPARPi (n=191), the HR for PFS was 0.74 (95% CI, 0.54-1.03, P=.0685). ORR in those who received mirvetuximab soravtansine was 45% (95% CI, 36%-54%), including 7 complete responses (CR), compared to 17% (95% CI, 11%-25%). The HR for OS was 0.90 (95% CI, 0.590-1.38; P=.6319).
In patients with 1 or 2 PLOT (n=245), the PFS HR was 0.61 (95% CI, 0.45-0.81; P=.0007). ORR in patients who received mirvetuximab soravtansine was 46% (95% CI, 37%-55%), including 10 CRs, compared to 15% (95% CI: 9%-22%), with no CRs, in patients who received IC chemotherapy (P<.0001). OS HR was 0.66 (95% CI, 0.45-0.98; P=.0375).
In patients who received 3 PLOT (n=208), PFS HR was 0.71 (95% CI, 0.52-0.98; P=.0362).ORR in patients who received mirvetuximab soravtansine was 38% (95% CI, 29%, 48%), including 2 CRs, compared to 18% (95% CI, 11%, 26%), with no CRs, in patients who received IC chemotherapy (P=.0009).OS HR was 0.65 (95% CI, 0.43, 0.96; P=.0308).
Mirvetuximab soravtansine's safety profile was also tolerable compared to IC chemotherapy. Low-grade ocular and gastrointestinal events were the most reported adverse events (AEs). The frequency of grade 3 or higher AE was 42% in patients who received mirvetuximab soravtansine and 54% in patients who received IC chemotherapy. The frequency of serious AEs was 24% in patients who received mirvetuximab soravtansine and 33% in patients who received IC chemotherapy. Frequency of treatment discontinuation due to a grade 3 or higher AE was 9% in patients who received mirvetuximab soravtansine and 16% in patients who received IC chemotherapy.
The MIRASOL study has an estimated study completion date of April 2024. Phase 3 of the GLORIOSA study (NCT05445778) is also evaluating the safety and efficacy of mirvetuximab soravtansine as maintenance therapy in patients with PROC.1