Elahere (mirvetuximab soravtansine-gynx)

P3, N=289, Recruiting, AstraZeneca | N=46 --> 289

P2/3, N=46, Not yet recruiting, AstraZeneca AB

We report a population of high FOLR1-expressing tumor-associated macrophages (CD163 + FOLR1 + ), suggesting potential on-target, off-tumor immune editing by MIRV. A composite biomarker score derived in this cohort correlates with objective response to MIRV and pembrolizumab.

Recently, the antibody-drug conjugate mirvetuximab soravtansine has been approved for treatment of advanced platinum-resistant high-grade serous carcinoma (HGSC)...In conclusion, these results confirm that FRα expression in HGSC and LGSC reaches similar values compared to published data, and is present in a minority of endometrial serous carcinomas. In other ovarian and endometrial tumors examined, FRα expression is absent or rare.

Collectively, VEGF-, PARP-, and FRα-targeted therapies have enabled more rational treatment sequencing, informed combination strategies, and personalized clinical decision-making in ovarian cancer. Ongoing efforts to define optimal sequencing, overcome acquired resistance, and refine predictive biomarkers are expected to further enhance the durability and breadth of benefit from targeted therapies and advance precision oncology in gynecologic malignancies.

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

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

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.

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.