sirtratumab vedotin (ASG-15ME) / Astellas - LARVOL DELTA

Systematic review of recent advancements in antibody-drug and bicycle toxin conjugates for the treatment of urothelial cancer. (PubMed, Ther Adv Urol) - "These initial studies led to FDA approval of two antibody-drug conjugates, enfortumab vedotin and sacituzumab govitecan...The combination of enfortumab vedotin and pembrolizumab was recently approved for first-line treatment of advanced urothelial carcinoma. Despite the great promise of these novel drugs, robust predictive biomarkers are needed to determine the patients who would maximally benefit. This review surveys the rationale and current state of the evidence for these new drugs and describes future directions actively being explored."

IO biomarker • Journal • Review • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • HER-2 • NECTIN4

Preclinical characterization of PRO1106, a novel and promising SLITRK6-directed sesutecan ADC (AACR 2024) - "Sesutecan previously demonstrated promising characteristics in preclinical studies with multiple targets and conferred an encouraging benefit:risk profile in the clinic with a FRα-directed ADC (rinatabart sesutecan)...Target-binding was superior to sirtratumab (the parent antibody in AGS15E) and the binding epitope appeared to be distinct from that of sirtratumab in cross-block studies...In summary, PRO1106 is an ADC built on a clinically validated linker-drug directed at a clinically validated target, with promising data in preclinical pharmacology studies. As SLITRK6 expression in skin is negligible, PRO1106 may offer an exciting new option for patients with bladder cancer where the current standard-of-care ADC therapy (enfortumab vedotin) confers significant skin-related toxicity burden as well as for patients with additional cancer types."

Preclinical • Bladder Cancer • Brain Cancer • Breast Cancer • CNS Tumor • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Genito-urinary Cancer • Glioblastoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • FOLR1 • SLITRK6

Efficacy and toxicity of antibody-drug conjugates in the treatment of metastatic urothelial cancer: A scoping review. (PubMed, Urol Oncol) - "ACDs represent a new therapeutic option for the treatment of mUC. Level-1 evidence has already been achieved by EV in the post-CT and post-ICI settings. A high incidence of potential adverse events was observed in phase 2 and 3 trials, including rash, neutropenia, hematologic toxicity, and neuropathy. Clinicians should be aware of possible adverse events and their optimal management."

Journal • Review • Bladder Cancer • Diabetes • Genito-urinary Cancer • Hematological Disorders • Immune Modulation • Inflammation • Neutropenia • Oncology • Pain • Solid Tumor • Urothelial Cancer

Efficacy and toxicity of antibody-drug conjugates (ADCs) in the treatment of metastatic urothelial cancer (mUC): A systematic review. (ASCO 2022) - "Ultimately, 9 phase 1, 2 or 3 clinical trials with 1355 patients were selected for inclusion and 4 drugs were identified: Enfortumab vedotin (EV), sacituzumab govitecan (SG), an anti-HER2 compound (RC48-ADC), and an anti- SLITRK6 drug (ASG-15ME). ACDs represent a very promising new option for the treatment of mUC. A phase 3 trial confirmed the superiority of EV over CT after platinum and IO failure. A high incidence of potential adverse events was observed in phase 2 and 3 trials, including rash, neutropenia, hematologic toxicity, and neuropathy."

Clinical • Review • Bladder Cancer • Diabetes • Genito-urinary Cancer • Hematological Disorders • Neutropenia • Oncology • Pain • Solid Tumor • Urothelial Cancer