An Open-label, Multi-center Dose Escalation Phase I Study to Investigate the Safety and Tolerability of a Continuous Infusion of the Bispecific T-cell Engager (BiTE) MT110 in Locally Advanced, Recurrent or Metastatic Solid Tumors Which Commonly Express EpCAM and Are Not Amenable to Curative Treatment
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Solid Tumors
- Sponsor
- Amgen Research (Munich) GmbH
- Enrollment
- 65
- Locations
- 4
- Primary Endpoint
- Overall frequency and intensity of adverse events (AEs) (clinical symptoms, laboratory abnormalities, serious adverse events [SAEs] and dose-limiting toxicities)
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
This phase I dose escalation study is intended to define the safety, tolerability and maximal tolerable dose (MTD) of MT110 in patients with advanced solid tumors.
Detailed Description
MT110 is a bispecific (anti-EpCAM x anti-CD3) T-cell engager (BiTE) designed to link EpCAM (epithelial cell adhesion molecule) expressing cells and T-cells resulting in T-cell activation and a cytotoxic T-cell response against EpCAM+ cells. In vitro and ex-vivo data indicate that EpCAM+ tumor cell lines are sensitive to MT110 mediated cytotoxicity. Furthermore, data from in-vivo experiments with both MT110 and a mouse surrogate molecule (muS110) have confirmed the activity of these molecules in inhibiting the formation of metastases but also against established tumors. In vitro and ex-vivo data suggest that a prolonged presence of the drug in target tissues may result in significant T-cell recruitment, activation and expansion to/in target tissues, potentially resulting in substantial anti-tumor activity in man.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Locally advanced, recurrent or metastatic solid tumors known to widely express EpCAM and proven histology of the following entities:
- •Adenocarcinoma of the lung
- •Small cell lung cancer (SCLC)
- •Gastric cancer or adenocarcinoma of gastro-esophageal junction
- •Colorectal cancer (CRC)
- •Hormone-refractory prostate cancer (HRPC)
- •Breast cancer
- •Ovarian cancer
- •Patients must not be amenable to curative therapy. Patients should have exhausted or declined standard therapeutic options and previous therapies should have included at least one course of chemotherapy.
- •Non-measurable disease or at least one measurable tumor lesion as per RECIST criteria
Exclusion Criteria
- •Evidence of central nervous system (CNS) metastases on baseline computer tomography (CT) or magnetic resonance imaging (MRI) scan (mandatory for all patients), current or past relevant history of other CNS pathology (except migraine, headache and minor incidental findings in the MRI without any clinical manifestation within the last five years). All minor incidental findings should be discussed with the Sponsor's Medical Monitor).
- •Neutrophil count \< 1,500/mm3 (= 1.5 x 10\^9/l)
- •Platelet count \< 100,000/mm3 (= 100 x 10\^9/l)
- •White blood cells (WBC) \< 3 x10\^9/l
- •Hemoglobin \< 9.0 g/dl
- •Abnormal renal or hepatic function as defined below:
- •Alkaline phosphatase (AP)\>/= 2.5 x upper limit of normal (ULN) and/or aspartate aminotransferase (AST, SGOT), alanin aminotransferase (ALT, SGPT) \>/= 2.0 x ULN or AP, AST and/or ALT \>/= 3 x ULN in case of liver metastases; γ-glutamyl transpeptidase (GGT) \>/= 5.0 x ULN
- •Total bilirubin \>/= 1.5 x ULN
- •Creatinine clearance \< 50 ml/min calculated by the Cockroft-Gault formula or MDRD (modification of diet in renal disease)
- •Lipase/amylase \> 1.5 x ULN
Outcomes
Primary Outcomes
Overall frequency and intensity of adverse events (AEs) (clinical symptoms, laboratory abnormalities, serious adverse events [SAEs] and dose-limiting toxicities)
Time Frame: one or more treatment cycles
Secondary Outcomes
- Pharmacokinetics of MT110; T-cell counts, kinetics, and activation status; Serum cytokine concentrations; Immunogenicity; Anti-tumor activity; Other progressive disease (PD) parameters(one or more treatment cycles)