P2, N=20, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Recruiting

P2, N=100, Recruiting, Shanghai Hengrui Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

P2, N=32, Not yet recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Jul 2027 --> Nov 2027 | Initiation date: Oct 2024 --> Feb 2025 | Trial primary completion date: Jul 2027 --> Nov 2027

Non-UC malignancies seem to have a lower N4 positivity rate than UC. N4 positivity in bladder cancer appears to vary according to stage and presence of HS. The predictive and prognostic role of N4 must be further characterized in larger and prospective studies.

Various studies demonstrated expression of Nectin-4 in many solid tumor entities with the highest expression rates in urothelial carcinomas and breast cancer. To date, the relevance of the subcellular compartment of immunoreactivity (membranous vs. cytoplasmic) is still unclear in respect of its predictive value for EV therapy, which ought to be clarified in further studies.

Enfortumab vedotin(EV)is an antibody-drug conjugate (ADC) targeting Nectin-4, which has been approved by FDA for the treatment of urothelial carcinoma...These therapies offer novel strategies for delivering targeted treatments to Nectin-4-expressing cancer cells, enhancing treatment efficacy and minimizing off-target effects. In conclusion, this review aims to provide an overview of the latest advances in understanding the role of Nectin-4 in breast cancer and discuss the future development prospects of Nectin-4 targeted agents.

P1/2, N=90, Recruiting, Shanghai Hengrui Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

P3, N=420, Recruiting, Mabwell (Shanghai) Bioscience Co., Ltd.

Among these therapies, erdafitinib, a pan-fibroblast growth factor receptor (FGFR) inhibitor for specific FGFR2 and FGFR3 alterations, is the only targeted therapy approved till now...Ongoing investigations exist on its use in non-muscle-invasive BC and in combination with drugs such as enfortumab vedotin in mUC...This review emphasizes the importance of FGFR inhibition in UC and the optimization of its use in clinical practice. Moreover, it underscores the ongoing efforts to evaluate combination strategies and early treatment testing to enhance the effectiveness of targeted therapies for UC.

Enfortumab vedotin demonstrated meaningful clinical activity with a manageable safety profile in Chinese patients with previously treated locally advanced or mUC.

P=N/A, N=22, Completed, Hospices Civils de Lyon

P1/2, N=124, Recruiting, Shanghai Hengrui Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

Significant differences were observed in PFS and OS among the three groups (p<0.001 and p<0.001, respectively) and c-indices were 0.766 for PFS and 0.800 for OS. The risk classification using CRP and hypercalcemia is useful for predicting the outcomes of patients with advanced UC treated with EV.

ADCs offer the opportunity for a more effective and personalized treatment approach for gynecologic cancer patients. Side effects must be closely monitored, and preventive measures must be followed to maximize benefit and minimize toxicity. A better understanding of the role of target proteins as biomarkers to predict response to ADCs will be critical for successful clinical implementation of ADCs and further research in this area is necessary.

The characterization of metastatic tumour samples can improve response prediction to immunotherapy, the anti-NECTIN4 antibody-drug conjugate enfortumab vedotin and the FGFR inhibitor erdafitinib. Routine metastatic biopsy can thus improve the precision of identifying driver druggable alterations, thus improving treatment selection for patients with mUC.

P=N/A, N=80, Recruiting, LMU Klinikum

ETx-22 has a highest non severely toxic dose of over 20 mg/kg in non-human primates without signs of important skin toxicity. ETx-22 represents a valuable therapy, for the treatment of patients with nectin-4 expressing tumors including those that have become resistant to enfortumab vedotin treatment.

P2, N=100, Not yet recruiting, Shanghai Hengrui Pharmaceutical Co., Ltd.

P2, N=20, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jun 2028 --> Jun 2029 | Trial primary completion date: Jun 2027 --> Jun 2028

Immunohistochemically abnormal p53 tumors were found to respond well to EV, while high FGFR3 tumors had a poorer response. Thus, p53 and FGFR3 are potential biomarkers for predicting response to EV treatment in patients with urothelial carcinoma.

P1/2, N=90, Not yet recruiting, Shanghai Hengrui Pharmaceutical Co., Ltd.

P1/2, N=41, Suspended, M.D. Anderson Cancer Center | Not yet recruiting --> Suspended

P1/2, N=47, Not yet recruiting, University of California, San Francisco | Trial completion date: Jun 2027 --> Sep 2027 | Initiation date: Aug 2024 --> Nov 2024 | Trial primary completion date: Jun 2027 --> Sep 2027

P2, N=40, Active, not recruiting, Astellas Pharma China, Inc. | Trial completion date: Sep 2024 --> Oct 2025

P1/2, N=124, Not yet recruiting, Shanghai Hengrui Pharmaceutical Co., Ltd.

P3, N=608, Active, not recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Aug 2024 --> Feb 2025

P1/2, N=19, Recruiting, University of Texas Southwestern Medical Center | Not yet recruiting --> Recruiting

P1/2, N=100, Recruiting, Mabwell (Shanghai) Bioscience Co., Ltd. | Not yet recruiting --> Recruiting

P3, N=420, Recruiting, Mabwell (Shanghai) Bioscience Co., Ltd. | Not yet recruiting --> Recruiting

P2, N=329, Active, not recruiting, Astellas Pharma Global Development, Inc. | Recruiting --> Active, not recruiting

P3, N=460, Recruiting, Mabwell (Shanghai) Bioscience Co., Ltd.

An anchored MAIC was conducted according to the National Institute for Health and Care Excellence Decision Support Unit guidance, with physician's choice of chemotherapy (docetaxel/paclitaxel and vinflunine) as the common comparator. The MAIC indicates comparable efficacy of erdafitinib vs EV for overall survival and progression-free survival, with erdafitinib showing a higher probability of achieving deep responses. While erdafitinib is associated with slightly more adverse events compared with EV, these events seem to be less severe.

P1/2, N=248, Recruiting, Shanghai Hengrui Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

P2, N=40, Not yet recruiting, H. Lee Moffitt Cancer Center and Research Institute

P1, N=30, Recruiting, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

P1, N=32, Recruiting, Emory University | Trial completion date: Jan 2025 --> Jan 2026

P1, N=58, Recruiting, Astellas Pharma Global Development, Inc. | Trial primary completion date: Jun 2024 --> Jun 2026

Patients without these factors had a significantly prolonged OS compared to those with both factors. In real-world practice, EV therapy is an effective treatment for patients with la/mUC after ICI treatment.

Median overall survival (OS) ranged from 12.1 to 31.5 months across the studies, with the combination of enfortumab vedotin and pembrolizumab demonstrating the most substantial reduction in the risk of death (HR 0.47 [95% CrI: 0.38, 0.58]), followed by avelumab monotherapy (HR 0.69 [95% CrI: 0.56, 0.86]). Avelumab showed notable single-agent activity. These findings provide a valuable framework to guide clinical decision-making and highlight priority areas for future research, including biomarker refinement and novel combination strategies to enhance antitumor immunity in this challenging malignancy.

In summary, EV may be effective in NECTIN-4-positive PCa. However, our findings demonstrate that the tumoural NECTIN-4 expression is predominantly low in metastatic PCa, which suggests that EV may only be effective in a biomarker-stratified subgroup.

Enfortumab vedotin and free MMAE exposures were statistically significant predictors of grade ≥ 3 treatment-related adverse events (both P < 0.0001). This analysis supports enfortumab vedotin 1.25 mg/kg on days 1, 8, and 15 of a 28-day cycle.

P1/2, N=248, Not yet recruiting, Shanghai Hengrui Pharmaceutical Co., Ltd.