MIRV shows promise in FRα-high, platinum-resistant ovarian cancer

The first-in-class antibody-drug conjugate mirvetuximab soravtansine (MIRV) shows promising anti-tumour activity in previously treated patients with platinum-resistant ovarian cancer who express high levels of folate receptor alpha (FRα), according to the SORAYA study presented at SGO 2022.

“Treatment options for platinum-resistant ovarian cancer are limited, consisting primarily of single-agent chemotherapy as many patients will have received prior bevacizumab,” explained lead author Dr Ursula Matulonis from the Dana-Farber Cancer Institute in Boston, Massachusetts, US.

“Single-agent chemotherapy has limited clinical activity and considerable toxicity,” she continued, noting that the objective response rate (ORR) of currently available agents ranged only around 4–13 percent.

Ovarian cancer overexpresses FRα, which has been associated with poor clinical outcomes, Matulonis pointed out. MIRV is a novel antibody-drug conjugate which consists of a FRα-binding antibody that targets the tubulin-targeting agent maytansinoid DM4 to tumour cells.

After a median follow-up of 8.5 months, the investigator-assessed ORR was 32.4 percent (95 percent confidence interval [CI], 23.6–42.2), which included five complete responses among the 105 evaluable patients — all of whom have previously received bevacizumab. [SGO 2022, abstract LBA 4]

ORR as assessed by blinded independent central review (BICR) yielded similar value (31.6 percent; 95 percent CI, 22.4–41.9), with five complete response as well.

The median progression-free survival spanned 4.3 months (95 percent CI, 3.7–5.1) as assessed by investigator and 5.5 months (95 percent CI, 3.8–6.9) as assessed by BICR.

“These results position MIRV to become a practice-changing, biomarker-driven standard of care treatment option for patients with FRα-positive platinum-resistant ovarian cancer,” said Matulonis.

Participants in the global, single-arm, phase III study were 106 patents with FRα-high, platinum-resistant ovarian cancer who had received 1–3 prior therapies. In the current study, they were treated with intravenous MIRV 6 mg/kg once every 3 weeks until disease progression or unacceptable toxicity.

When the analysis was stratified by previous therapies, the findings remained consistent regardless of whether the patient had 1–2 prior lines of therapy or three lines of therapy (ORR, 35.3 percent vs 30.2 percent). Similar ORR results were seen irrespective of whether patients had prior exposure to a PARP inhibitor or not (38.0 percent vs 27.5 percent).

The key secondary endpoint of duration of response (DOR) as assessed by investigator lasted a median of 6.9 months (95 percent CI, 5.6–8.1). The median DOR as assessed by BICR was 11.7 months (95 percent CI, 5.0 to not reached).

Again, the median DOR was consistent regardless of the number of lines of prior therapy (5.9 vs 7.0 months) and prior exposure to PARP inhibitor (5.7 vs 5.9 months).

Treatment-related adverse events (TRAEs) of any grade were reported in 86 percent of patients, but most of the AEs were low-grade, reversible ocular and gastrointestinal events, according to Matulonis.  The most common TRAEs were blurred vision (41 percent for any grade and 6 percent for grade ≥3), keratopathy (36 percent and 9 percent, respectively), and nausea (29 percent and none, respectively).

“In platinum-resistant ovarian cancer, where current therapies are suboptimal and biomarker selected treatment has not been successfully developed, FRα expression predicts benefit from MIRV,” said Matulonis.

“MIRV demonstrates clinically meaningful and durable anti-tumour activity with favourable tolerability in patients with high FRα regardless of number of prior therapies or prior [exposure to] PARP inhibitor,” she concluded. “[Thus,] MIRV represents an important advance for this biomarker selected population.”