P3, N=530, Active, not recruiting, Genmab | Recruiting --> Active, not recruiting

P3, N=520, Recruiting, AbbVie | Trial completion date: Apr 2029 --> May 2032

P1, N=256, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting | N=423 --> 256

In this real-world cohort, the addition of bevacizumab to mirvetuximab was associated with improved progression-free survival despite lower FRα expression, supporting potential synergy between these agents. Combination therapy may be considered for appropriately selected patients with FRα-expressing platinum-resistant ovarian cancer.

P1/2, N=37, Recruiting, AbbVie Deutschland GmbH & Co. KG

P1/2, N=121, Recruiting, AbbVie Deutschland GmbH & Co. KG

P1, N=34, Recruiting, AstraZeneca AB

Currently, three ADCs have received Food and Drug Administration (FDA) approval for use in gynecologic malignancies: mirvetuximab soravtansine, tisotumab vedotin, and trastuzumab deruxtecan. Furthermore, the inherent complexities of these drugs and their mechanisms of action underscore the need for further research into the relevance of biomarkers, methods of therapy resistance, and the potential for re-utilization of payloads and targets later in the disease course. This review focuses on the mechanisms of action of ADCs, their developmental trajectory, successes in gynecologic cancers, emerging areas of investigation, the prospective landscape, and current challenges in the field.

P1, N=24, Recruiting, AstraZeneca

All the pyrrolobenzodiazepines tested - SJG136, SGD-1882, SG2057, and SG3199 - were substrates of P-gp, ABCG2, and MRP1. The modified anthracyclines nemorubicin and its metabolite PNU-159682 were poorly transported by both ABCB1 and ABCG2 and displayed nanomolar to picomolar toxicity. Further, we found that the efficacy of the FDA-approved ADC mirvetuximab soravtansine, with DM4 as the toxic payload, was decreased in cell lines expressing P-gp... Several commonly used ADC payloads can be transported by ABC transporters, potentially leading to transporter-mediated drug resistance in patients. Future ADCs should be developed using payloads that are not ABC transporter substrates.

Finally, any-grade ocular adverse events (OAEs) are particularly common in patients during MIRV treatment, arising in 125 (57 %); grade ≥3 in 34 (16 %), most frequently, blurred vision (18 [8 %]), keratopathy (21 [10 %]), cataract (11 [5 %]), and dry eye (8 [4 %]); however, fortunately, over 90 % with OAEs had either full resolution or documented final grade 1 or better. The current review also discusses OAE, based on its high incidence, frequent cause responsible to dose reduction and delaying therapy with impacting 11-35 % of patients and of the most importance, relative unfamiliarity to most gynecological oncologists in the routine clinical practice.

P2, N=240, Recruiting, Genmab | Not yet recruiting --> Recruiting