ASG 5ME / Pfizer - LARVOL DELTA

Recent advances in antibody-drug conjugates for metastatic castration-resistant prostate cancer. (PubMed, Zhejiang Da Xue Xue Bao Yi Xue Ban) - P3 | "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..."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HER-2 • SLC44A4 • SLC4A4 • STEAP1

Discovery of a novel Nectin4 IPSC-derived cell therapy for the treatment of solid tumors (AACR 2024) - "Enfortumab vedotin, an antibody drug conjugate targeting Nectin4 positive tumors, has demonstrated benefit in clinical trials and is FDA approved for treatment of advanced bladder cancer...The lead CARs engineered into primary T-cells demonstrated tumor inhibition similar to a reference CAR using the ASG-5ME antibody (Enfortumab) as the Nectin4 binder. The CARs were engineered into our IPSC-derived iNK and iT cells and demonstrated cytotoxicity activity against a panel of cell lines with a range of cell surface expression of Nectin4. Based on these studies, Century Therapeutics is advancing the lead Nectin4 binder for development of an IPSC-derived cell therapy to treat Nectin4 positive solid tumors."

Bladder Cancer • Genito-urinary Cancer • Head and Neck Cancer • Oncology • Solid Tumor • NECTIN1 • NECTIN2 • NECTIN4

A phase 1 clinical trial of ASG-5ME, a novel drug-antibody conjugate targeting SLC44A4, in patients with advanced pancreatic and gastric cancers. (PubMed) - Invest New Drugs - "All patient biopsies (23 pancreatic, 15 gastric) expressed the SLC44A4 antigen. Conclusions ASG-5ME treatment was generally well tolerated with limited evidence of antitumor activity."

Journal • Biosimilar • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer

A phase 1 dose escalation trial of ASG-5ME in pancreatic adenocarcinoma (clinicaltrials.gov) - P1, N=35; Recruiting -> Active, not recruiting; N=72-> 35

Enrollment • Enrollment closed • Pancreatic Cancer

A phase I study of the antibody drug conjugate ASG-5ME, an SLC44A4-targeting antibody carrying auristatin E, in metastatic castration-resistant prostate cancer. (PubMed, Invest New Drugs) - "However, other toxicities were consistent with studies of previous MMAE-containing ADCs. Unconjugated MMAE is a less likely etiology based on prior data."

Journal • P1 data