Tivdak (tisotumab vedotin-tftv)

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.

P3, N=686, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Oct 2028 --> Jun 2028 | Trial primary completion date: Oct 2028 --> Jun 2028

These developments reflect a shift toward precision medicine that integrates immunotherapy, antiangiogenic, and targeted agents; however, challenges persist in optimizing treatment sequences, overcoming resistance, and identifying biomarkers to personalize care. Addressing global disparities in prevention and treatment access remains essential to achieving the WHO's goal of eliminating cervical cancer by 2030.

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.

Ocular adverse events (AEs) are common among ADCs with tubulin-targeted active agents, such as belantamab mafodotin, tisotumab vedotin and mirvetuximab soravtansine (MIRV). Support from ophthalmologists is essential to AE management to allow MIRV therapy to continue. This review provides ophthalmologists with a clinical overview of ocular AEs associated with certain tubulin-acting ADCs, with a focus on MIRV, and the prophylactic/mitigative measures that can allow patients to stay on MIRV therapy longer.

Among prostate-specific membrane antigen (PSMA)-targeted ADCs, ARX517 demonstrates superior safety and more significant prostate-specific antigen (PSA) reductions compared to earlier agents such as MLN2704, PSMA-ADC, and MEDI3726. ADCs targeting B7-H3, such as MGC018 and DB-1311, have also shown antitumor activity. ADCs targeting other antigens, including six-transmembrane epithelial antigen of the prostate (STEAP)1 (DSTP3086S), trophoblast cell surface antigen (TROP)2 (sacituzumab govitecan), and solute carrier (SLC) 44A4 (ASG-5ME), have shown preliminary antitumor activity in early trials but face challenges with insufficient efficacy or toxicity. Tisotumab vedotin (targeting tissue factor) has shown no significant therapeutic response in mCRPC. Meanwhile, disitamab vedotin (HER2-targeted), ABBV-969 (dual PSMA/STEAP1-targeted), and DXC008 (dual PSMA/STEAP1-targeted) are currently under evaluation. Notably, the B7-H3-targeted ADC ifinatamab deruxtecan has initiated an international multicenter phase Ⅲ clinical trial (NCT06925737) for mCRPC in May 2025. This review summarizes recent advances in ADCs targeting key antigens in mCRPC (including PSMA, B7-H3, STEAP1, TROP2, SLC44A4, and others) and explores combination strategies, offering insights to inform the clinical management of this highly lethal disease.