Mirvetuximab Soravtansine Displays Promising Efficacy in Platinum-Resistant Ovarian Cancer

Ursula A. Matulonis, MD

Patients with platinum-resistant ovarian cancer have historically been an underserved population with few effective treatment options. However, a new option for these patients whose disease harbors a high level of folate receptor α (FRα) may be emerging as the first-in-class antibody-drug conjugate mirvetuximab soravtansine displayed promising antitumor activity, according to results from the phase 3 SORAYA trial (NCT04296890) presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.¹

Efficacy-evaluable patients (n = 105) experienced an investigator-assessed overall response rate (ORR) of 32.4% (95% CI, 23.6%-42.2%), including a 4.8% complete response (CR) rate. The investigator-assessed median duration of response (DOR) was 6.9 months (95% CI, 5.6-9.7) and the median time to response was 1.5 months (range, 1.0-5.6). The disease control rate (DCR) was 51.4% (95% CI, 41.5%-61.3%), with a 71.4% tumor reduction rate.

Additionally, the median investigator-assessed progression-free survival (PFS) was 4.3 months (95% CI, 3.7-5.2). The median overall survival (OS) was 13.8 months (95% CI, 12.0-not estimable), although study authors noted that the data is still immature and is descriptive in nature.¹

“The results from SORAYA position were mirvetuximab soravtansine to become a practice-changing therapy for patients with platinum-resistant ovarian cancer [that is] high-grade serous and FRα positive, in a place in treatment where patients have very few options,” said Ursula A. Matulonis, MD, in an interview with OncologyLive^®.Mirvetuximab soravtansine is a well-tolerated drug for patients who have responses, and those responses are durable. They are deep responses, where we saw complete responses, which is really an unheard-of phenomenon in the treatment of platinum-resistant ovarian cancer.”

Based on the data from SORAYA, the FDA accepted and granted priority review to the biologic license application for mirvetuximab soravtansine and is expected to decide by November 28, 2022. To validate the findings, investigators have initiated the randomized phase 3 randomized MIRASOL trial (NCT04209855) vs investigator’s choice chemotherapy.^2,3

In our discussion, Matulonis, who is the chief of the Division of Gynecologic Oncology at Dana-Farber Cancer Institute in Boston, Massachusetts, talked through the key findings of the study.

What were the objectives of the SORAYA trial and what inspired this research?

SORAYA was launched to examine a patient population where we thought that mirvetuximab soravtansine would have a very good opportunity [for efficacy]. Mirvetuximab soravtansine is an antibody-drug conjugate against the FRα. We have learned from previous randomized phase 3 studies is that in order for this drug to optimally work, there has to be high levels of expression of FRα.

The key objective of the research was confirmed ORR. [This included] confirmed ORR by the investigator and a blinded independent central review analysis [of] response rates and PFS. The overall primary end point was confirmed response rate, as assessed by the investigator, and a key secondary end point was the DOR. We also looked at PFS, toxicities, and OS.

What methods were used to conduct the SORAYA trial?

The key eligibility criteria for the trial were that all patients had to have platinum-resistant ovarian cancer as assessed by the investigator, [with] high-grade serous histology, and they had to have received prior bevacizumab [Avastin]. Importantly [patients also] had to have high levels of expression of FRα.

[High FRα expression] was determined by [immunohistochemistry] PS2 [scoring]; 75% or higher of the cells that stained positive with 2+ or higher staining. This was assessed by central pathology. Patients received the antibody-drug conjugate mirvetuximab soravtansine as a single agent [at] 6 mg/kg intravenously and the dose was determined by ideal body weight. Patients received the drug once every 3 weeks. There were 106 patients on the trial.

What did you find notable about the efficacy findings in SORAYA?

In terms of outcomes and efficacy data, the investigator-assessed ORR was 32.4%— these are all confirmed responses by RECIST 1.1 [criteria]. Also, we saw 5 patients who had CRs and in this patient population, who are heavily pretreated, have received bevacizumab, and all had platinum-resistant cancer, it is very unusual. In fact, it is extremely rare to see CRs with single-agent, nonplatinum-based chemotherapy. We were really grateful to see those 5 CRs.

The subgroup analysis looked at number of prior lines of treatment [2 vs 3] and whether patients had received a prior PARP inhibitor. [There were] no differences in ORR. If that patient had or had not received a prior PARP inhibitor, that did not appear to influence the ORR.

The median DOR was 6.9 months. Also, the same [observations were maintained when] looking at the different subgroup analyses. The median DOR was 6.9 months, or very close, regardless of number prior lines of treatment, or whether or not the patient had received a PARP inhibitor.

The DCR was 54%. The tumor reduction rate, so any patient who had [measurable disease by] RECIST 1.1, showed a tumor reduction of 75%. These were new data presented at ASCO.

What adverse effects (AEs) were observed among patients treated with mirvetuximab soravtansine?

The toxicity data that we saw in SORAYA is very comparable to what has been seen in other mirvetuximab soravtansine trials. Most of the AEs were low grade. Most of them were reversible ocular and gastrointestinal toxicities. We saw minimal peripheral neuropathy and no alopecia.

Patients who developed an ocular AE, approximately 55%, [mostly experienced a] low grade. All patients at the beginning of the trial had a baseline ocular exam. If they developed an ocular toxicity during the trial, then an ophthalmology exam was instituted every 2 cycles. Very few patients needed dose reductions because of ocular toxicities.

What effect could this agent have on the treatment landscape in this patient population?

For our patients with platinum-resistant ovarian cancer and have also received bevacizumab, their option for treatment is single-agent, nonplatinum-based chemotherapy. [This includes] topotecan and gemcitabine. These drugs typically have low response rates—12% or lower—more often than not in the single agents.

The data that we saw from SORAYA represents a clinically meaningful anticancer activity for this patient population, who, unfortunately, have very few options. This should be a new standard of care for patients with platinum-resistant, high-grade serous ovarian cancer, where there is high FRα expression within the cancer.

Reference

1. Matulonis UA, Oaknin A, Pignata S, et al. Mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: characterization of antitumor activity in the SORAYA study. J Clin Oncol. 2022;40(suppl 16):5512. doi:10.1200/JCO.2022.40.16_suppl.5512
2. ImmunoGen announces acceptance of biologics license application for mirvetuximab soravtansine in ovarian cancer by US Food and Drug Administration with priority review. News release. ImmunoGen, Inc. May 23, 2022. Accessed July 1, 2022. bit.ly/3MV4Amt
3. A study of mirvetuximab soravtansine vs. investigator’s choice of chemotherapy in platinum-resistant, advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha expression (MIRASOL). ClinicalTrials.gov. Updated June 16, 2022. Accessed July 1, 2022. https://clinicaltrials.gov/ct2/show/NCT04209855