ASP1650 / Astellas - LARVOL DELTA

177Lu-Labeled Anticlaudin 6 Monoclonal Antibody for Targeted Therapy in Esophageal Cancer. (PubMed, J Nucl Med) - "The radiotracer [89Zr]Zr-DFO-IMAB027 showed high contrast when visualizing CLDN6-expressing xenografts for PET imaging, and [177Lu]Lu-DOTA-IMAB027 induced rapid tumor regression in both the TE-1-CLDN6 and the CLDN6-PDX models. This research has implications for improving the radioligand diagnosis and treatment of EC."

Journal • Esophageal Cancer • Oncology • CLDN6

Targeting Esophageal Cancerfor Imaging and Therapy Using Claudin 6 Radioligands (EANM 2024) - "CLDN6 has a high expression rate in esophageal cancer and is a promising target for imaging and radioligand therapy. 89Zr-IMAB027 showed high contrast to visualize CLDN6 expressing xenografts for PET imaging, and 177Lu-IMAB027 induced rapid tumor regression in a preclinical model of EC."

Esophageal Cancer • Gastrointestinal Cancer • Oncology • CLDN6

A phase II study assessing the safety and efficacy of ASP1650 in male patients with incurable platinum refractory germ cell tumors. (ASCO-GU 2020) - P2; " This phase 2 study with a safety run-in (NCT03760081) will enroll ≤46 male patients (pts) with advanced GCTs who have had prior cisplatin-based combination chemotherapy and ≥1 salvage regimen. Clinical trial information: NCT03760081. Research Funding: Astellas Pharma Inc."

Clinical • P2 data • Genito-urinary Cancer • Germ Cell Tumors • Oncology • Testicular Cancer

A phase II study assessing the safety and efficacy of ASP1650 in male patients with relapsed refractory germ cell tumors. (PubMed, Invest New Drugs) - P2 | "CLDN6 expression seems ubiquitous in all elements of GCT and is worthy of investigation as a diagnostic biomarker and therapeutic target. (Clinical trial information: NCT03760081)."

Journal • P2 data • Genito-urinary Cancer • Germ Cell Tumors • Oncology • Solid Tumor • Testicular Cancer • CLDN6

Phase 1 Trial of IMAB027 in Patients With Recurrent Advanced Ovarian Cancer (OVAR) (clinicaltrials.gov) - P1; N=42; Completed; Sponsor: Ganymed Pharmaceuticals GmbH; N=72 ➔ 42

Clinical • Enrollment change • Oncology • Ovarian Cancer • Solid Tumor • CLDN6 • MUC16

A phase II study assessing the safety and efficacy of ASP1650 in male patients with incurable platinum refractory germ cell tumors. (ASCO-GU 2020) - P2; " This phase 2 study with a safety run-in (NCT03760081) will enroll ≤46 male patients (pts) with advanced GCTs who have had prior cisplatin-based combination chemotherapy and ≥1 salvage regimen. Clinical trial information: NCT03760081. Research Funding: Astellas Pharma Inc."

Clinical • P2 data • Genito-urinary Cancer • Germ Cell Tumors • Oncology • Testicular Cancer

[VIRTUAL] CLDN6 and CLDN9 dual targeting antibody drug conjugates for the treatment of ovarian and endometrial cancers (AACR 2021) - "Both candidates demonstrated superior antibody-mediated antigen internalization than ASP1650, the forerunner in clinical trials. GB7008-03 and GB7008-05 also showed good ADCC potency on CLDN6 expressing tumor cell lines. Currently we are developing antibody-drug-conjugates based on these two antibodies. In vivo efficacy of these ADCs in CDX models will be presented."

Embryonal Tumor • Endometrial Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • Testicular Cancer • CLDN6

Preclinical characterization of the safety and antitumor activity of IMAB027-vcMMAE, an anticlaudin 6 antibody-drug conjugate (AACR 2018) - "Repeated dosing of IMAB027vcMMAE was well tolerated in mice, with no physical abnormalities, changes in behavior, or alterations in appearance observed.Conclusions IMAB027vcMMAE is a specific antibodydrug conjugate against CLDN6 that induces potent antitumor activity in CLND6+ tumor cells in vitro and in vivo. Furthermore, IMAB027vcMMAE was able to induce antitumor effects in tumors with low and/or heterogeneous target expression, which may be driven by bystander activity."

IO Biomarker • Genito-urinary Cancer

Claudin 6 is a carcinoembryonic antigen with cancer stem cell marker features (AACR 2018) - "...A monoclonal antibody against CLDN6, IMAB027, has shown promising antitumor activity in preclinical human CLDN6-positive (CLDN6+) cancer models...Analysis of OC metastases in mouse xenografts showed when xenografts were generated by OC cells that had <10% of CLDN6+ cells, the metastases were enriched in CLDN6+ cells, suggesting CLDN6+ cells had selective growth advantage.Conclusions CLDN6 is a cancer cell-specific surface molecule aberrantly expressed in several cancers, and its expression may be an identifier for cells with CSC-like traits. These characteristics make CLDN6 an attractive target candidate for tumor-specific therapeutic antibodies."

Cancer stem cells • IO Biomarker • Genito-urinary Cancer • Lung Cancer • Ovarian Cancer

The anti-claudin 6 antibody, IMAB027, induces antibody-dependent cellular and complement-dependent cytotoxicity in claudin 6-expressing cancer cells (AACR 2018) - "Xenografted mouse tumors with human CLDN6+ cells were generated to investigate the in vivo antitumor effects of IMAB027 both as a single agent and in combination with chemotherapeutic agents such as paclitaxel. IMAB027 binds specifically to CLDN6 without cross-reactivity with other closely related family members, such as Claudins 3, 4, and 9. IMAB027 binds specifically to CLDN6 without cross-reactivity with other closely related family members, such as Claudins 3, 4, and 9. IMAB027 induced target-selective ADCC and CDC in a number of CLDN6+ ovarian and testicular cancer cell lines; median EC50 values for ADCC and CDC were of the order of ng/mL in representative cell lines. Direct induction of apoptosis did not appear to be a contributor to the antitumor effect of IMAB027."

Genito-urinary Cancer • Ovarian Cancer • Uterine Cancer

"🎉Congrats @UR_Med #VAD program on 200 less invasive LVAD implants! We invite VAD staff from OR->CICU->434->512->714 to socially distanced😷celebration! #lvad #css #lis #hm3 #eras #roc @URMCSurgery @AbbottNews @urvascularsurg @DocDiastole @chrissiecheyne" (@URMed_AHF)

A Study to Assess the Safety and Efficacy of ASP1650, a Monoclonal Antibody Targeting Claudin 6 (CLDN6), in Male Subjects With Incurable Platinum Refractory Germ Cell Tumors (clinicaltrials.gov) - P2; N=19; Completed; Sponsor: Astellas Pharma Global Development, Inc.; Recruiting ➔ Completed; N=46 ➔ 19; Trial completion date: Feb 2021 ➔ Oct 2020; Trial primary completion date: Feb 2021 ➔ Oct 2020

Clinical • Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Germ Cell Tumors • Oncology • Solid Tumor • AFP

A Study to Assess the Safety and Efficacy of ASP1650, a Monoclonal Antibody Targeting Claudin 6 (CLDN6), in Male Subjects With Incurable Platinum Refractory Germ Cell Tumors (clinicaltrials.gov) - P2; N=46; Recruiting; Sponsor: Astellas Pharma Global Development, Inc.; Trial completion date: Oct 2022 ➔ Feb 2021; Trial primary completion date: Sep 2022 ➔ Feb 2021

Clinical • Trial completion date • Trial primary completion date • Germ Cell Tumors • Oncology • Solid Tumor • AFP

A Study to Assess the Safety and Efficacy of ASP1650, a Monoclonal Antibody Targeting Claudin 6 (CLDN6), in Male Subjects With Incurable Platinum Refractory Germ Cell Tumors (clinicaltrials.gov) - P2; N=46; Recruiting; Sponsor: Astellas Pharma Global Development, Inc.; Active, not recruiting ➔ Recruiting

Clinical • Enrollment open • Gastrointestinal Cancer • Germ Cell Tumors • Oncology • Solid Tumor • AFP

A Study to Assess the Safety and Efficacy of ASP1650, a Monoclonal Antibody Targeting Claudin 6 (CLDN6), in Male Subjects With Incurable Platinum Refractory Germ Cell Tumors (clinicaltrials.gov) - P2; N=46; Active, not recruiting; Sponsor: Astellas Pharma Global Development, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Gastrointestinal Cancer • Genito-urinary Cancer • Germ Cell Tumors • Oncology • Solid Tumor

A Study to Assess the Safety and Efficacy of ASP1650, a Monoclonal Antibody Targeting Claudin 6 (CLDN6), in Male Subjects With Incurable Platinum Refractory Germ Cell Tumors (clinicaltrials.gov) - P2; N=46; Recruiting; Sponsor: Astellas Pharma Global Development, Inc.; Trial completion date: May 2021 ➔ Oct 2022; Trial primary completion date: Apr 2021 ➔ Sep 2022

Clinical • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Genito-urinary Cancer • Germ Cell Tumors • Oncology • Solid Tumor