vandortuzumab vedotin (RG7450) / Roche - 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

DXC008, a novel STEAP1 antibody-tubulysin analog conjugate with a function linker, demonstrates a potential to broaden therapeutic opportunities for prostate tumors (AACR 2024) - "A Steap1 antibody called Vandortuzumab conjugated with MMAE (DSTP3086S) was in the clinical phase I trial for treating STEAP1-expressing metastatic castration-resistant prostate cancer and showed acceptable safety at 2.4 mg/kg once every 3 weeks. Pharmacokinetic profiles of DXC008 were favorable and the safety of Maximal Tolerable Dose (MTD) was over 120 mg/kg in single injection in mice. DXC008 has been forward to NHP toxicity study and it has potential to be a good STEAP1/PSMA-targeting ADC with a wide therapeutic window for prostate cancers."

Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1 • STEAP1

Study of 89Zr-DFO-MSTP2109A in Patients With Prostate Cancer (clinicaltrials.gov) - P1/2; N=27; Active, not recruiting; Sponsor: Memorial Sloan Kettering Cancer Center; Trial completion date: Jan 2021 ➔ Jan 2022; Trial primary completion date: Jan 2021 ➔ Jan 2022

Clinical • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • STEAP1

The search for a prostate cancer magic bullet - "Researchers from the Memorial Sloan Kettering Institute in the US have recently published a 'first in humans' trial of a magic bullet drug targeting prostate cancer through STEAP1. The research group were led by eminent oncologist and researcher Prof Howard Scher. Their experimental drug has been made to target prostate cancer through STEAP1 proteins. The drug uses an antibody that recognises STEAP1. This antibody is attached to a toxin to kill the cancer cells. They have helpfully labelled the new drug as DSTP3086S."

Novel theranostic reagent could enhance detection and therapy of prostate cancer (Eurekalert) - "A recently discovered prostate cancer-selective antigen has been identified as a useful molecular imaging target for the detection and targeting of metastatic prostate cancer lesions, as reported...As researchers were unable to biopsy all cancerous lesions, a Bayesian approach was used to apply information gleaned from biopsied lesions to project the number of cancerous lesions in each patient....The authors of 'Imaging Patients with Metastatic Castration-Resistant Prostate Cancer Using 89Zr-DFO-MSTP2109A Anti-STEAP1 Antibody' include...Howard I. Scher..."

Phase I Study of DSTP3086S, an Antibody-Drug Conjugate Targeting Six-Transmembrane Epithelial Antigen of Prostate 1, in Metastatic Castration-Resistant Prostate Cancer. (PubMed, J Clin Oncol) - "DSTP3086S has acceptable safety at the recommended phase II dose level of 2.4 mg/kg once every 3 weeks. Antitumor activity at doses between 2.25 and 2.8 mg/kg once every 3 weeks supports the potential benefit of treating STEAP1-expressing metastatic castration-resistant prostate cancer with an STEAP1-targeting antibody-drug conjugate."

Journal • P1 data • Anorexia • Constipation • Diabetes • Fatigue • Gene Therapies • Genito-urinary Cancer • Oncology • Pain • Prostate Cancer • Renal Disease • Solid Tumor

Pharmacokinetics and Biodistribution of [89Zr]Zr-DFO-MSTP2109A Anti-STEAP1 Antibody in Metastatic Castration-Resistant Prostate Cancer Patients. (PubMed, Mol Pharm) - "The pharmacokinetics were similar to other antibodies without major cross-reactivity with normal tissues. A more detailed analysis of lesion targeting in a larger patient population with correlation to immunohistology and standard imaging modalities has been reported."

Clinical • Journal • PK/PD data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Imaging metastatic castration-resistant prostate cancer patients with Zr-DFO-MSTP2109A anti-STEAP1 antibody. (PubMed, J Nucl Med) - "Zr-DFO-MSTP2109A is well tolerated and shows localization in mCRPC sites in bone and soft tissue. Given the high SUV in tumor and localization of a large number of lesions, this reagent warrants further exploration as a companion diagnostic in patients undergoing STEAP1-directed therapy."

Clinical • Journal

Study of 89Zr-DFO-MSTP2109A in Patients With Prostate Cancer (clinicaltrials.gov) - P1/2; N=27; Active, not recruiting; Sponsor: Memorial Sloan Kettering Cancer Center; Trial completion date: Jan 2020 ➔ Jan 2021; Trial primary completion date: Jan 2020 ➔ Jan 2021

Clinical • Trial completion date • Trial primary completion date

Phase I study of DSTP3086S, an antibody-drug conjugate targeting six-transmembrane epithelial antigen of prostate 1, in metastatic castration-resistant prostate cancer (J Clin Oncol) - P1, N=84; NCT01283373; Sponsor: Genentech; "Among 62 patients who received > 2 mg/kg DSTP3086S once every 3 weeks, 11 (18%) demonstrated a ≥ 50% decline in prostate-specific antigen; two (6%) of 36 with measurable disease at baseline achieved a radiographic partial response; and of 27 patients with informative unfavorable baseline circulating tumor cells ≥ 5/7.5 mL of blood, 16 (59%) showed conversions to favorable circulating tumor cells < 5. No prostate-specific antigen or RECIST responses were seen with weekly dosing."

P1 data