upifitamab rilsodotin (XMT-1536)

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.

P1, N=62, Completed, Mersana Therapeutics

P1, N=142, Completed, Mersana Therapeutics

P1/2, N=523, Active, not recruiting, Mersana Therapeutics | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1/2

P3, N=20, Terminated, Mersana Therapeutics | N=350 --> 20 | Trial completion date: Mar 2025 --> Sep 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Sep 2024 --> Sep 2023; Study Terminated by Sponsor

P1, N=31, Terminated, Mersana Therapeutics | N=48 --> 31 | Trial completion date: Mar 2025 --> Oct 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Nov 2024 --> Oct 2023; Study Terminated by Sponsor

P1, N=48, Active, not recruiting, Mersana Therapeutics | Recruiting --> Active, not recruiting

P3, N=350, Active, not recruiting, Mersana Therapeutics | Recruiting --> Active, not recruiting

In ovarian cancer, mirvetuximab soravtansine, an ADC targeting alpha-folate receptor (FRα), received US Food and Drug Administration (FDA) accelerated approval in November 2022 after data from the single-arm phase III SORAYA trial. A second ADC targeting FRα, STRO-002, received FDA fast track designation in August 2021. Multiple studies with upifitamab rilsodotin, an ADC comprising a NaPi2B-binding antibody, are underway. In cervical cancer, tisotumab vedotin, an ADC-targeting tissue factor, received FDA accelerated approval in September 2021 after the phase II innovaTV 204 trial...Trastuzumab-deruxtecan (T-DXd), an ADC targeting human epidermal growth factor receptor 2 (HER2), is currently approved for HER2-positive and HER2-low breast cancer and shows promise in endometrial cancer. Like all anticancer treatments, the decision for a patient to undergo therapy with an ADC is a personal choice that balances the potential benefits with the side effects and requires thorough and compassionate support of their physician and care team and shared decision making.

NCT04907968. Clinical trial information: NCT04907968.