MIL-38/Gallium67 / GlyTherix - LARVOL DELTA

Determination of optimal imaging dose of [89Zr]Zr-DFO-Miltuximab and maximum tolerated therapeutic of [177Lu]Lu-DOTA-Miltuximab (EANM 2024) - "Biodistribution data from the first in human trial of [67Ga]Ga-DOTA-Miltuximab was used to determine an optimal imaging dose of 50-75MBq for [89Zr]Zr-DFO-Miltuximab and 6GBq as the predicted maximum tolerated dose of [177Lu]Lu-DOTA-Miltuximab."

Pharmacokinetics and Biodistribution of Zr-Miltuximab and Its Antibody Fragments as Glypican-1 Targeting Immuno-PET Agents in Glioblastoma. (PubMed, Mol Pharm) - "Results from in vivo PET image quantification and ex vivo scintillation counting were highly correlated. Altogether, Zr-DFO-Miltuximab appears to be an effective immuno-PET imaging agent for detecting GPC-1 tumors such as GBM and the current results support utility of the Fc containing whole mAb format over smaller antibody fragments for this target."

Journal • PK/PD data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • GPC1

Clinical development of an anti-GPC-1 antibody for the treatment of cancer. (PubMed, Expert Opin Biol Ther) - "Clinical development of novel anti-GPC-1 antibody-based formats is still in its early days. Using the patented anti-GPC-1 Miltuximab® as a case study, we have made an attempt to illustrate a pathway for pre-clinical to clinical translation, which could be useful for newer GPC-1 targeting immunotherapy agents."

IO biomarker • Journal • Oncology • Solid Tumor • GPC1

"#GlyTherix awarded NSW Government TechVoucher to evaluate efficacy of our #Cancer #Antibody #Miltuximab https://t.co/Qn5D7hxxTS" (@1stOncology)

Clinical • Oncology

Glypican-1 as a target for fluorescence molecular imaging of bladder cancer. (PubMed, Int J Urol) - "The highly specific accumulation and retention of Miltuximab-IRDye800CW in glypican-1-expressing tumors in vivo shows its high potential for fluorescence imaging of urothelial carcinoma and warrants its further investigation toward clinical translation."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • GPC1

Safety and tolerability of Miltuximab - a first in human study in patients with advanced solid cancers. (PubMed, Asia Ocean J Nucl Med Biol) - "[Ga]Ga-DOTA-Miltuximab targeting to tumour sites was observed in two prostate cancer patients who had failed enzalutamide treatment. The trial met its primary endpoint of safety, demonstrating its potential as a safe and tolerable monoclonal antibody. This safety data, together with targeting to tumour lesions and biodistribution information supports the further clinical development of Miltuximab as a theranostic agent in a planned Phase I human trial."

Clinical • Journal • P1 data • Genito-urinary Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Urothelial Cancer

A bispecific T cell engager targeting Glypican-1 redirects T cell cytolytic activity to kill prostate cancer cells. (PubMed, BMC Cancer) - "This study reports preclinical findings into the efficacy of targeting GPC-1 in PCa with BiTE construct MIL-38-CD3. We show the specificity and efficacy of the construct, supporting its further preclinical development."

IO Biomarker • Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • GPC1 • IFNG • IL2RA • PD-1

The feasibility of Miltuximab®-IRDye700DX-mediated photoimmunotherapy of solid tumors. (PubMed, Photodiagnosis Photodyn Ther) - "PIT with Miltuximab®-IR700 appears to be highly specific and effective against GPC-1-expressing cancer cells, indicating that it holds promise for an effective and safe treatment of early stage solid tumors or as adjuvant therapy following surgical resection. These findings necessitate further investigation of PIT with Miltuximab®-IR700 in other GPC-1-expressing cancer cell lines in vitro and in vivo in xenograft tumor models."

IO Biomarker • Journal • Oncology • Ovarian Cancer • Solid Tumor • GPC1

Targeted beta therapy of prostate cancer with Lu-labelled Miltuximab® antibody against glypican-1 (GPC-1). (PubMed, EJNMMI Res) - "These findings demonstrate the potential utility of Miltuximab® as a PET imaging agent ([Zr]Zr-DFO-Miltuximab®) and a beta therapy ([Lu]Lu-DOTA-Miltuximab®) in patients with PCa or other GPC-1 expressing tumours."

Journal

Near-Infrared Molecular Imaging of Glioblastoma by Miltuximab-IRDye800CW as a Potential Tool for Fluorescence-Guided Surgery. (PubMed, Cancers (Basel)) - "Ex vivo assessment of Miltuximab-IR800 biodistribution confirmed its highly specific accumulation in the tumor. The results of this study confirm that Miltuximab-IR800 holds promise for intraoperative fluorescence molecular imaging of GBM and warrants further studies."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • GPC1

Proposed Study Design for a Miltuximab Phase 1 Trial 89Zr/177Lu theranostic trial (PCF 2019) - P1, N=12; "The first in human for Miltuximab demonstrated its potential for further clinical evaluation as a theranostic in prostate cancers and formed the basis for a Phase I imaging and therapy study planned for 2020. This study will use 89Zr-labelled Miltuximab to screen eligible patients and confirm tumour localisation, followed by treatment with 177Lu-labelled Miltuximab."

P1 data