89Zr-AMG211 PET Imaging Study

Study Overview
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Brief Summary
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AMG 211 is a bispecific single-chain antibody construct of the bispecific T-cell engager (BiTE®) class that targets human carcinoembryonic antigen (CEA, CD66e) on (tumor) cells and cluster of differentiation 3 (CD3) positive T-cells. AMG 211 is a potentially new targeted drug in the treatment of relapsed/refractory gastrointestinal adenocarcinoma, since those are CEA expressing tumors. A well-known challenge in current drug development using targeted therapies is the high level of heterogeneity of target expression that is present in specific tumor types. Radio-labeling of AMG 211 with the positron emission tomography (PET) radionuclide Zirconium-89 (89Zr) enables non-invasive imaging and quantification of AMG 211 distribution in cancer patients. By performing a 89Zr-AMG211 PET scan prior to treatment with AMG 211, the uptake of the tracer in the primary and metastatic tumor lesions and normal organ distribution can be evaluated. By performing a 89Zr-AMG211 PET scan during AMG 211 continuous intravenous (cIV) treatment the investigators will be able to evaluate the impact of prolonged steady state exposure of AMG 211 on tumor and tissue uptake. The 89Zr-AMG211 PET imaging study may help to identify patients more likely to benefit from AMG 211 therapy.

Official Title
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89Zr-AMG211 PET Imaging in Patients With Relapsed/Refractory Gastrointestinal Adenocarcinoma Before and During Treatment With AMG 211

Conditions
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Advanced Gastrointestinal Cancer

Intervention / Treatment
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* Drug: 89Zr-AMG211
* Device: 89-ZrAMG211 PET


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject will or is also participating in the ongoing phase 1 study in which AMG 211 is administered via cIV. 89Zr-AMG211 PET imaging will be performed before and/or during treatment with AMG 211 cIV Informed consent provided Male or Female ≥ 18 years of age at the time of informed consent Advanced relapsed/refractory gastrointestinal adenocarcinoma At least 1 measurable tumor lesion o In case the investigators do not find any uptake in metastatic liver lesions in the first set of patients on the 89Zr-AMG211 PET scan, than subsequent patients need to have at least 1 measurable tumor lesion outside the liver Archival tumor tissue available or is willing to undergo biopsy of a tumor lesion before the start of treatment Adequate hematological, renal, and liver function Body weight ≥ 45 kg Other inclusion criteria may apply Exclusion Criteria: Malignancy other than GI adenocarcinoma requiring current therapy Evidence of uncontrolled systemic disease (other than GI adenocarcinoma), active infection, Hepatitis B and/or C, HIV, history of cardiac disease, history of significant central nervous system (CNS) disease, history of chronic autoimmune disease (with the exception of stable type 1 diabetes) Major surgery within 28 days of study day 1 Currently receiving treatment in another investigational device or drug study, or less than 28 days since ending treatment in another investigational device or drug study. Other investigational procedures while participating in this study are excluded. o Exception to this criterion is the participation in the currently ongoing phase 1 study with AMG 211 cIV and all procedures related to this study. Treatment with any chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal therapy for cancer within 14 days prior to study entry or not recovered from treatment Unresolved toxicities from prior anti-tumor therapy Males or Females of reproductive potential and unwilling to practice an acceptable method of effective birth control while on study through 30 days after receiving the last dose of study drug. Females who are pregnant, planning to become pregnant, lactating/breastfeeding or who plan to breastfeed while on study through 30 days after receiving the last dose of study drug Other exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 89Zr-AMG211 and 89Zr-AMG211 PET<br> | Drug: 89Zr-AMG211<br>* Injection of 89Zr-AMG211 for imaging.<br>Device: 89-ZrAMG211 PET<br>* 89Zr-AMG211 PET scan(s).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The quantitative uptake op 89Zr-AMG211 in tumor tissue, organs and blood circulation expressed in SUV (Standardized Uptake Value) |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to AMG 211 therapy according to the immune related response criteria (irRC) will be correlated to 89Zr-AMG211 tumor uptake data (measured in SUV). |  | 1 year | 
| Number of patients with adverse events after 89Zr-AMG211 injection as a measure of safety and tolerability. Incidence, nature and severity of adverse events (according to CTCAE version 4.03) will be measured. |  | 1 year |