Detailed Description:
The primary objective is to determine the biodistribution of radiolabeled amatuximab in tumor and nontumor tissues in subjects with mesothelin over-expressing cancers including mesothelioma, pancreatic, ovarian, and non small cell lung cancer. This is a single-center, single-dose, open-label, pilot study of amatuximab in approximately 20 subjects with mesothelin expressing tumors. Unlabeled amatuximab will be administered at a low dose (50 mg) to saturate any nonspecific binding and shed antigen. Within 6 hours after cold antibody infusion, 111Indium-radiolabeled amatuximab (5 mCi) will be administered. Serial SPECT imaging (at 3 specific time points up to 196 hours after cold infusion) will be performed to determine binding to tumor and nontumor tissue. Subjects will be observed closely for safety and possible development of anti-amatuximab antibodies. Pharmacokinetics of radiolabeled antibody will be determined with imaging over time.
Primary Outcome Measures:
- Primary Objective: determine biodistribution of radiolabeled amatuximab in tumor and nontumor tissue [ Time Frame: 1 year ] [ Designated as safety issue: No ]
To determine the biodistribution of radiolabeled amatuximab in tumor and nontumor tissue in subjects with mesothelin over expressing cancer including mesothelioma, pancreatic, ovarian or nonsmall cell lung cancer by performing SPECT imaging to determine binding to tumor and non-tumor tissue.
Secondary Outcome Measures:
- Secondary objectives: determine the safety of a single IV of Indium-CHX-A amatuximab [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
To determine the safety of a single IV of Indium-CHX-A amatuximab by collecting safety data during/ after the infusions as well as obtain any potential drug-related AEs 30 days post infusion - Pharmacokinetic and serum levels [ Time Frame: 1 year ] [ Designated as safety issue: No ]
To determine the PK parameters of the Indium-CHX-A amatuximab with imaging, and serum levels collected over time - uptake of Indium-CHX-A amatuximab [ Time Frame: 1 year ] [ Designated as safety issue: No ]
To explore the uptake of Indium-CHX-A amatuximab with mesothelin tumor expression as determined by ICH - occurrence of HACA [ Time Frame: 1 year ] [ Designated as safety issue: No ]
To tabulate the occurrence of HACA which will be measured through serum samples collected over time - correlate shed serum mesothelin to imaging [ Time Frame: 1 year ] [ Designated as safety issue: No ]
To correlate shed serum mesothelin to imaging obtained after antibody administration.
Eligibility Criteria
- Inclusion Criteria:
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- Female and Male subjects > or = 18 years of age
- Histologically confirmed mesothelin-expressing cancer
- Measurable disease that has progressed through prior therapy and that includes a non-hepatic lesion for imaging that is > or = 1.5cm, as defined by RECIST v1.1 and disease location, at discretion of the physician, or evaluable by clinical symptoms supported by biomarker, radiological or pathological studies conducted within 4 weeks prior to study entry
- Exclusion Criteria:
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- Known allergy or hypersensitivity to monoclonal antibodies
- Known to develop HACA
- Prior treatment with amatuximab
- Prior treatment with SS1 (dsFv)PE38 (ss1P)
- Prior treatment with another test article within previous 30 days
- Known brain metastasis
- Known prosthetic devices that would prohibit imaging ow lesion of interest due to radiographic artifact
- Chemotherapy, biological therapy, radiation therapy or immunotherapy within 3 weeks prior to dosing with amatuximab
