MILGa-01: a first-in-human study assessing the safety and tolerability of chMIL-38 in metastatic prostate, bladder, and pancreatic cancers

Howard Gurney, Dhanusha Sabanathan, David Gillatt, Pirooz Poursoultan, Kevin Ho Shon, Brad Walsh, Vicki Velonas, Kristofer Thurecht, Douglas Campbell

Research output: Contribution to journalMeeting abstract

Abstract

Background: Metastatic or recurrent cancer continues to be a challenge in patients with urogenital and pancreatic cancers despite the development of newer anti-androgen therapies. MIL-38 is an IgG1 murine monoclonal antibody directed against Glypican-1 (GPC-1). The proteoglycan GPC-1 is upregulated in prostate, pancreatic and bladder cancer cell lines. Targeting of tumor xenografts and lack of adverse events in pre-clinical models suggest chimeric MIL-38 (chMIL-38) is a good candidate for both radioimmunotherapy and antibody-drug conjugate development.

Methods: Patients with known metastatic prostate and pancreatic cancer were injected with a single dose of MILGa drug (1mg, 250MBq dose) and imaged with whole body gamma camera scans and SPECT/CT at 30 minutes, 6 h, 24 h, 48 h, 72 h (if required) and 144h post infusion. Blood and urine samples for pharmacokinetic, biomarker studies, cancer markers and hematology and biochemistry analysis were collected at each time point. Dosimetry analysis of tumour images was performed to determine the relative accumulation of MILGa in different organs.

Results: To date one pancreatic cancer patient and one prostate cancer patient with metastatic disease have been infused with the MILGa drug. The drug was safe and well tolerated in both patients with no infusion reactions or drug-related adverse events. Tracer uptake was observed in the liver, with mild tracer uptake in the spleen, skeletal system and kidneys. Significant MILGa targeting was seen in Patient 2 24 hours post infusion onwards with uptake in the right foot (right calcaneum and cuneiform bones). SPECT/CT at 24 hours confirmed uptake was in the bone, not in the joint space or soft tissue.

Conclusions: MILGa has shown a promising safety profile to date with indication of tumour targeting in metastatic prostate cancer. Additional data from this study may permit the selection and evaluation of potentially sensitive tumor types to be studied for further therapeutic and diagnostic studies. Clinical trial information: ACTRN12616000787482.
Original languageEnglish
Article numbere565
Number of pages1
JournalJournal of Clinical Oncology
Volume35
Issue number6
DOIs
Publication statusPublished - 2017

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