First Targeted Drug Receives FDA Approval for Chemotherapy-Resistant Ovarian Cancer

Developed by Immunogen, mirvetuximab soravtansine-gynx, marketed as Elahere, is for patients whose cancer has become resistant to platinum-based chemotherapy after 1 to 3 previous lines of treatment and who have folate receptor-alpha (FRa)-positive advanced epithelial ovarian, fallopian tube or primary peritoneal cancer. It received accelerated US Food and Drug Administration (FDA) approval on 14 November 2022.

Elahere is the first FDA-approved antibody–drug conjugate for platinum-resistant ovarian cancer.

The approval covers patients whose tumours are folate receptor-alpha (FRa)-positive and who have received one to three previous systemic treatment regimens, regardless of prior bevacizumab use (Altuzan, Mvasi, Zirabev).

FRa Positivity in Ovarian Cancer: 35-40%

On the same date, the FDA also approved Roche’s Ventana FOLR1 RxDx Test, a companion diagnostic to help identify patients eligible for Elahere. Approximately 35-40% of patients with ovarian cancer are strongly FRa-positive: this means staining at 2+ intensity in 75% or more of tumour cells. Testing can use fresh tissue or archived paraffin blocks. Newly diagnosed patients may be tested at diagnosis to determine whether Elahere could become an option if platinum resistance develops.

The Importance of Ovarian Cancer and the Need for New Treatments

Ovarian cancer, according to Türkiye Cancer Statistics 2020, is the 15th most common cancer, with 4059 new cases annually. Because early disease causes no symptoms and there is no effective screening method, most patients present with advanced-stage (3, 4) cancer. The main treatment is surgery followed by platinum-based chemotherapy. Unfortunately, most patients eventually develop difficult-to-treat platinum-resistant disease. Once resistance develops, standard treatment is single-agent chemotherapy, associated with low response rates, short response duration and substantial adverse effects. Platinum-resistant ovarian cancer is challenging to treat. Given the absence of new FDA-approved treatments for these patients since 2014, Elahere’s accelerated approval represents a major advance. For platinum-sensitive disease, newer drugs in the PARP inhibitor class had already made important contributions. 

How Does Elahere (Mirvetuximab Soravtansine-gynx) Work?

ELAHERE (mirvetuximab soravtansine-gynx) is a first-in-class antibody–drug conjugate comprising a folate receptor-alpha-binding antibody, a cleavable linker and maytansinoid DM4 chemotherapy, a potent tubulin inhibitor designed to kill targeted cancer cells.

Elahere’s accelerated approval reflects decades of work developing a new generation of antibody–drug conjugates. We can expect to hear of many more approvals for these agents in cancer treatment.

What Is an Antibody–Drug Conjugate?

Antibody–drug conjugates use a Trojan horse approach: an antibody designed to bind a molecular target on the tumour is attached to a chemotherapy agent, allowing delivery to a particular tumour cell.

SORAYA: The Study Behind Elahere’s FDA Approval

Elahere was approved under the FDA’s accelerated approval programme on the basis of objective response rate and response duration in SORAYA. Conversion to full approval may depend on confirmation and characterisation of clinical benefit in a subsequent study.

Elahere’s effectiveness was evaluated in the pivotal, single-arm SORAYA study in 106 patients with platinum-resistant ovarian cancer, high tumour FRa expression and one to three previous systemic treatment regimens. The primary endpoint was investigator-assessed objective response rate, and the key secondary endpoint was response duration.

Results

• Mirvetuximab soravtansine produced an objective response rate of 31.7%, including five complete responses (95% confidence interval [CI]: 22.9, 41.6).
• Median response duration was 6.9 months (95% CI: 5.6, 9.7).

Adverse Effects

Elahere’s prescribing information includes a boxed warning for ocular toxicity, including visual impairment, keratopathy, dry eye, photophobia, eye pain and uveitis. The most common adverse effects, including laboratory abnormalities (in ≥20% of patients), were visual impairment, fatigue, increased aspartate aminotransferase, nausea, increased alanine aminotransferase, keratopathy, abdominal pain, decreased lymphocytes, peripheral neuropathy, diarrhoea, decreased albumin, constipation, increased alkaline phosphatase, dry eye, decreased magnesium, decreased leukocytes, decreased neutrophils and decreased haemoglobin.

Dose

The recommended mirvetuximab soravtansine-gynx dose is 6 mg/kg by intravenous infusion every three weeks (a 21-day cycle), until progression or unacceptable toxicity.

Key data from MIRASOL, the confirmatory randomised trial designed to convert accelerated approval to full approval, are expected in early 2023.