NECTIN4 expression

The Bicycle® toxin conjugate (BTC) zelenectide pevedotin, formerly known as BT8009, is a novel bicyclic peptide targeting the Nectin-4 tumor antigen conjugated to the cytotoxin monomethyl auristatin E (MMAE) via a valine-citrulline cleavable linker...The method was validated according to local standard operating procedures and has met all US Food and Drug Administration and European Medicines Agency regulatory guidance criteria. A bioanalytical method for measuring zelenectide pevedotin in plasma samples was developed and successfully applied in evaluating over 3000 samples from patients in a Phase 1/2 clinical study of zelenectide pevedotin in patients with advanced solid tumors.

Our results revealed a low spatial heterogeneity of Nectin-4 expression within the primary tumour. In contrast, differential Nectin-4 expression was found in the context of histological and molecular subtypes. Nectin-4-expressing tumours may show varying sensitivity to both EV and platinum-based chemotherapy.

Notably, NECTIN-4 TAC28-T cells exhibited better anti-tumor effects both in vitro and in vivo than the original NECTIN-4 TAC-T cells. Our data highlighted that NECTIN-4 TAC28-T cells may represent a promising, safe and effective cell therapy for NECTIN-4-overexpressing solid tumors.

Exosomal PVRL4 promoted LUAD progression by inducing the secretion of TGF-β1 in MDSCs, indicating a novel direction for LUAD immunotherapy.

P1, N=30, Recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Sep 2025 | Trial primary completion date: Oct 2024 --> Sep 2025

Biodistribution studies validated the specific binding of Al18F-N231 to nectin-4 in vivo, with tumor uptake in the nectin-4+ SW780 tumor group being 1.45- and 3.75-fold higher than that in the nectin-4- 5637 tumor group and blocking group, respectively. Based on the results of this work, Al18F-N231 has promising capability for noninvasive nectin-4 detection in vivo.

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.

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.

P1/2, N=329, Recruiting, BicycleTx Limited | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

We have engineered a Nectin-4 NDC with elevated affinity and effective tumor uptake, further establishing its potential as a therapeutic agent for gastric cancer.