These recommendations aim to promote integrated, equitable, standardized FRα testing across Canada and support timely identification of patients eligible for FRα-directed therapy, clinical trial enrollment, and future biomarker-driven treatment strategies.

Three ADCs are currently approved for previously treated gynaecological cancers: mirvetuximab soravtansine for folate receptor-α-positive ovarian cancer, trastuzumab deruxtecan for solid tumours expressing HER2 (defined as a staining intensity on immunohistochemistry of 3+) and tisotumab vedotin for cervical cancer (independent of tissue factor expression). Moreover, rational combinations could reinforce and extend the clinical potential of these agents, as has already been demonstrated with the addition of ADCs to immune checkpoint inhibitors in an effort to amplify antitumour immunity and prolong the durability of clinical responses. In this Review, we provide an overview of the current landscape of ADCs in gynaecological malignancies, highlighting key advances and future opportunities.

P3, N=1630, Recruiting, Eli Lilly and Company | N=1080 --> 1630 | Trial primary completion date: Apr 2028 --> Nov 2028

P3, N=520, Active, not recruiting, AbbVie | Trial primary completion date: May 2032 --> Apr 2027

Platinum-based chemotherapy increased Cyclin-E1 expression. These patients were less likely to benefit from PARP inhibitors (75% are BRCA-wildtype) or mirvetuximab-soravtansine (67% were not FRα-high), highlighting a distinct patient population in need of novel therapies.

P2, N=110, Recruiting, AbbVie | Trial primary completion date: Mar 2028 --> Jul 2026

P3, N=520, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting | Trial primary completion date: Apr 2027 --> May 2032

P3, N=82, Not yet recruiting, Genmab

Cataracts represent an under-recognized ocular adverse event associated with mirvetuximab soravtansine-gynx treatment. Although the etiology remains unclear, potentially related to mirvetuximab soravtansine-gynx exposure, ocular corticosteroids, or both, the frequency and tempo observed in this cohort underscore the need for close ophthalmologic monitoring. However, it is reassuring that cataracts can be treated with a minimally invasive procedure with generally excellent outcomes. Further research is warranted to elucidate underlying mechanisms and optimize supportive eye care strategies.

MIRV showed anticipated pharmacokinetics, safety, tolerability, and efficacy profiles in Chinese patients with FRα-positive platinum-resistant ovarian cancers, supporting its potential as a targeted therapeutic agent for this patient population.

MIRV is highly likely to be a more effective treatment option than the chemotherapies currently available for patients with FRα-positive, platinum-resistant ovarian cancer, as approximately 75-90% of ovarian cancers are FRα-positive. However, in the current circumstances, MIRV is unlikely to be considered cost-effective within the German healthcare context without reduction in the drug price.

P2/3, N=311, Not yet recruiting, Eli Lilly & Co.