Elahere (mirvetuximab soravtansine-gynx)

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.

The analysis focuses on treatments that have demonstrated clinical benefit in advanced or recurrent disease, including pembrolizumab, dostarlimab, tisotumab vedotin, and mirvetuximab soravtansine. Their growing integration into clinical practice has reshaped therapeutic approaches, while ongoing research continues to refine optimal combinations, address resistance, and enhance biomarker-guided selection. Future developments are expected to unite immunologic, genomic, and computational strategies to achieve personalized and durable outcomes for patients with gynecologic malignancies.

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.

In advanced ovarian cancer, TRUST re-examined surgical timing, supporting primary cytoreduction in selected resectable patients, whereas ICON8B suggested that weekly paclitaxel with carboplatin and bevacizumab may improve outcomes in high-risk disease. Platinum-resistant ovarian cancer saw the most disruptive progress: mirvetuximab soravtansine validated folate receptor-α as a therapeutic target, with overall survival benefit in high-expressing tumors; trastuzumab deruxtecan expanded actionable HER2 disease, with greatest activity in tumors rated 3+ by immunohistochemistry; and combination strategies, including relacorilant plus nab-paclitaxel and pembrolizumab plus weekly paclitaxel ± bevacizumab, delivered clinically meaningful survival signals, underscoring the need for harmonized biomarker strategies and proactive toxicity mitigation...In cervical cancer, pembrolizumab added to definitive chemoradiotherapy set a new benchmark in locally advanced disease, and ultra-sensitive circulating tumor DNA analyses emerged as a powerful prognostic tool to enable post-treatment risk-adapted strategies. Collectively, the 2025 data set reinforces a "right therapy, right patient, right time" paradigm and prioritizes confirmatory antibody-drug conjugate trials, resistance biology, and dynamic biomarkers to translate gains into durable, equitable benefit.

P3, N=1100, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting

Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate (ADC) composed of the DM4 payload conjugated to a folate receptor α (FRα)-targeting antibody via the cleavable sulfo-SPDB linker. The MIRV Phase 3 registrational trial (MIRASOL) showed superiority of MIRV vs. chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan) in patients with high (≥ 75%) FRα-expression PROC, showing an objective response rate of 42% versus 16%, a median progression-free survival of 5.6 versus 4.0 months, and an overall survival of 16.5 versus 12.8 months. Here, we briefly review MIRV mechanism of action, pharmacokinetics, pharmacodynamics, and key clinical efficacy and safety data.

The success of inhibitors like sotorasib and adagrasib has expanded options for targeting once 'undruggable' oncogenic drivers such as KRAS...ADCs such as EMRELIS™, Datroway, and ELAHERE™ offer precise targeting along with potent cytotoxic agents...Cancer vaccine research is progressing with licensed immunoprophylactic drugs, and AI tools like AlphaFold are speeding up drug discovery by enhancing structural biology predictions. This review covers recent cancer therapeutics advancements, including targeted inhibitors, immunotherapies, resistance strategies, epigenetic interventions, combination therapies, vaccines, and AI applications.