P1, N=150, Not yet recruiting, Nanolattix Biotechnology Co., Ltd.

P3, N=502, Completed, Seagen, a wholly owned subsidiary of Pfizer | Active, not recruiting --> Completed | Trial completion date: May 2026 --> Jan 2026

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.

P=N/A, N=20, Not yet recruiting, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Sun Yat-sen Memorial Hospital, Sun Yat-sen University

For locally advanced disease, KEYNOTE-A18 establishes pembrolizumab plus chemoradiation as a new curative standard, while INTERLACE underscores the benefit of induction chemotherapy. In the metastatic setting, survival outcomes have improved with the integration of checkpoint inhibitors (KEYNOTE-826, BEATcc, EMPOWER-Cervical 1), vascular-targeted therapies, and antibody-drug conjugates, including tisotumab vedotin and emerging HER2 and TROP-2-directed agents...Future directions include neoadjuvant checkpoint inhibition, PARP-IO combinations, HER3-directed ADCs, DDR-targeted radiosensitizers, HPV-specific cellular therapies, and AI-integrated precision medicine. Collectively, these advances are reshaping cervical cancer care toward biologically individualized, globally implementable strategies capable of accelerating WHO elimination targets.

P2, N=352, Active, not recruiting, Seagen, a wholly owned subsidiary of Pfizer | Trial completion date: Sep 2026 --> Mar 2027

The simultaneous or sequential presentation of cervical and breast cancer is rare, especially under systemic treatment. The patient's cervical cancer was aggressive, and the subsequent metachronous breast cancer highlights the complex, multifactorial nature of carcinogenesis. The development of a second primary malignancy while a patient is receiving treatment for a metastatic condition is a critical clinical scenario, necessitating individualized treatment strategies, as optimal management remains unclear due to the rarity of such cases.

Particularly, the combination of platinum-based chemotherapy and pembrolizumab, with or without bevacizumab, has been established as the new standard treatment for primary metastatic or recurrent PD-L1 positive high-risk cervical cancer. In locally advanced cervical cancer, two new treatment escalation regimens-neoadjuvant chemotherapy and adjuvant CPI therapy-have been evaluated in addition to chemoradiation. Furthermore, antibody-drug conjugates, such as tisotumab-vedotin, represent a promising future therapeutic option for recurrent cervical cancer.

P1, N=200, Recruiting, Sutro Biopharma, Inc.

P2, N=352, Active, not recruiting, Seagen, a wholly owned subsidiary of Pfizer | Trial primary completion date: Sep 2025 --> Jan 2026

For cervical, vulvar and vaginal cancers specifically, trastuzumab deruxtecan and tisotumab vedotin could be important therapeutic options in the right context. In this review, we describe the molecular features of different cervical, vulvar and vaginal cancer types, current genomically-matched therapies being investigated and discuss treatment strategies with future potential.

Agents such as mirvetuximab soravtansine, and tisotumab vedotin, targeting folate receptor alpha and tissue factor, respectively, reported clinical efficacy in patients with limited options. Comprehensive management of ocular toxicities is essential to ensure the safe and sustained use of ADCs, preserving both therapeutic benefit and patient well-being. Further research is warranted to optimize preventive and management protocols.