Tivdak (tisotumab vedotin-tftv)

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.

Currently, mirvetuximab soravtansine and tisotumab vedotin have been approved by the Food and Drug Administration for the treatment of folate receptor-alpha-positive, platinum-resistant ovarian cancer and recurrent cervical cancer, respectively, exhibiting promising objective response rates and manageable toxicity profiles in pivotal clinical trials...Additionally, multiple investigational ADCs, such as upifitamab rilsodotin (targeting NaPi2b), trastuzumab deruxtecan (targeting HER2), and sacituzumab govitecan (targeting trophoblast cell surface antigen 2), have demonstrated preliminary efficacy in ongoing clinical trials, offering new therapeutic opportunities for gynecologic malignancies. This review comprehensively summarizes the current clinical applications and research progress of ADCs in gynecologic cancers, including key clinical trials, therapeutic efficacy, safety profiles, and associated challenges. Furthermore, we discuss future optimization strategies, including the identification of novel targets, rational combination therapies, and molecular design improvements to advance ADC-based precision treatment in gynecologic oncology.

With the approval of tisotumab vedotin (TV), a tissue factor (TF)-targeting ADC, for the treatment of r/mCC, an increasing number of ADCs targeting different antigens have demonstrated highly encouraging therapeutic potential in cervical cancer patients...This review outlines promising tumor-associated antigens (TAAs) for ADC targeting in cervical cancer and their biological functions, such as human epidermal growth factor receptor 2 (HER2), trophoblast cell surface antigen 2 (Trop-2), mesothelin, nectin cell adhesion molecule 4 (Nectin-4). We also summarize the clinical applications and research progress of corresponding ADC, and provide novel perspectives for future ADC development and clinical research strategies.

P4, N=100, Recruiting, Pfizer | Not yet recruiting --> Recruiting