Mirvetuximab Soravtansine Accelerated Approval Helps Fill Unmet Need in Platinum Resistant Ovarian Cancer

The accelerated approval of mirvetuximab soravtansine-gynx (Elahere) for folate receptor α (FRα)-positive, platinum-resistant epithelial ovarian, fallopian tube, or peritoneal cancer marks a significant shift in the treatment paradigm as it is the first antibody-drug conjugate (ADC) approved for ovarian cancer.¹

The regulatory decision was supported by data from the phase 3 SORAYA trial (NCT04296890) in which evaluable patients (n = 104) achieved an investigator-assessed objective response rate (ORR) of 31.7% (95% CI, 22.9%-41.6%). The median duration of response (DOR) was 6.9 months (95% CI, 5.6-9.7). Five patients (4.8%) achieved a complete response (CR), 29 had a partial response (27.6%), 48 (46.2%) had stable disease, and 20 patients (19.2%) experienced disease progression.^1,2

“[These are] very significant results,” Ursula A. Matulonis, MD, said in an interview with OncologyLive^®. “We’re thankful and grateful to the FDA for granting an accelerated approval for this medication because our patients need new therapies. [Mirvetuximab soravtansine] is very active even in platinum resistant patients; where [previously] non platinum based chemotherapy response rates were 10% or less, we’re seeing at least triple of that [now with rates of] 32%.”

Matulonis, chief of the Division of Gynecologic Oncology and Brock-Wilson Family Chair at Dana-Farber Cancer Institute, as well as a professor of medicine at Harvard Medical School, both in Boston, Massachusetts, discussed the novelty of mirvetuximab soravtansine in this space and how it will expand options for a traditionally difficult-to-treat population.

What is the significance of this approval?

Matulonis: Mirvetuximab soravtansine is the first ADC that’s been approved for ovarian cancer and it’s one of the first biomarker-driven treatments [as] bevacizumab [Avastin] does not have a biomarker. The recognition that high levels of expression of FRα are critical for the efficacy and activity of mirvetuximab soravtansine is important because we can preselect patients [for treatment]. [For example,] for patients with recurrent disease, [we can] start to do FRα testing early on so if and when it’s appropriate for the patient to receive mirvetuximab soravtansine she is already screened. [It is also important to] make sure the FRα expression high, not low or medium.

How does this agent support unmet needs in the platinum resistant space?

The issue with platinum-resistant ovarian cancer is that it’s difficult to treat. As ovarian cancer becomes recurrent, then platinum-sensitive, with each [subsequent] treatment the cancer becomes platinum-resistant, and each treatment thereafter has less efficacy. If there’s some type of response [to therapy], that [duration of response] DOR and the amount of time in remission drops down.

Platinum-resistant ovarian cancer has been a challenging [space for the] discovery of active agents. The addition of bevacizumab [Avastin] to nonplatinum chemotherapy has certainly been quite effective. [But now] PARP inhibitors should not be used in platinum-resistant disease, [as] the previous FDA approvals in patients with BRCA mutations regardless of platinum sensitivity have been pulled by the 3 companies. [Therefore, our options in this space are], bevacizumab added to nonplatinum-based chemotherapy, and mirvetuximab soravtansine.

This approval opens up the opportunity for other novel therapies, potentially other ADCs, that can be used post mirvetuximab soravtansine, but not all cancers will have high levels of FRα expression. [The approval is] a huge step because it says we can find treatments that are effective and safe for patients with platinum-resistant ovarian cancer, and more clinical trials and research are needed to continue to develop effective treatments for [this population].

What is the pivotal efficacy data from the SORAYA trial?

In SORAYA, we enrolled 106 patients with FRα-positive, platinum-resistant ovarian cancer of high-grade serious histology, and all patients had received prior bevacizumab. Approximately 50% of patients had received a prior PARP inhibitor and patients received mirvetuximab soravtansine as a single agent and then at dose of 6 mg/kg once every 3 weeks.

The primary end point was confirmed ORR via the investigator [and a] secondary end point was DOR. There were pre specified subgroups [stratified by] how many prior lines patients had received and whether they had received a PARP inhibitor. The requirement was that patients could have received up to 3 prior lines of treatment and a little over half of patients had received up to 3 prior lines.

The ORR was 32.4%, as assessed by the investigator and confirmed by blinded independent review [among 104 evaluable patients]. There were no significant differences, which make this study very strong and enabled the accelerated approval to occur. The 2 prespecified subgroups did not significantly influence the response [and] even patients who had received up to 3 prior lines had a response rate a little over 30% [which was] reassuring of this medication.

The median DOR was 6.9 months [and] coupled with the 5 CRs, these are clinical numbers and clinical results that are not seen with nonplatinum chemotherapy such as single-agent topotecan, single-agent liposomal doxorubicin, where response rates are significantly less than 10%.

With SORAYA we received accelerated approval [and] in order to receive full approval, MARISOL will serve as the confirmatory phase 3 trial [NCT04209855].

What common toxicities can arise with the use of this agent?

Most toxicities were grade 1 and 2 and these were ocular toxicities—a bit of blurred vision that is completely reversible. [Additionally, a patient’s] eye specialist may notice keratopathy, which are corneal changes. These were all low grade as well and completely reversible.

We saw low-level [gastrointestinal] GI toxicity, which is nausea and because of the DM4 toxin we would be concerned about peripheral neuropathy, but we did not see significant neuropathy even in patients who received previous taxanes. Most of the neuropathy, if it occurred, was low grade at 12% [and] none of that was grade 3 or 4. [There was] a drop in blood counts, and we must watch out for that, and check counts when the patient comes in. Overall, it is an incredibly well tolerated drug.

References

1. FDA grants accelerated approval to mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or peritoneal cancer. FDA. Updated November 14, 2022. Accessed November 18, 2022. bit.ly/3GBHFFg
2. Elahere. Prescribing information. ImmunoGen Inc; 2022. Accessed November 18, 2022. bit.ly/3OhfjCa