131Iodine-Tenatumomab Treatment in Tenascin-C Positive Cancer Patients

This will be an open-label dose escalation study. The study will be conducted in two steps:

1. STEP A aims to identify the optimal amount of antibody to convey the specific radio-label activity of radionuclide.
2. STEP B will be conducted with the amount of antibody chosen in STEP A, and an escalating radio-labeled therapeutic dose response curve will be performed (3.5 to 5.5 GBq) A maximum of 36 evaluable patients suffering from treatment-refractory Tenascin-C positive tumors.

This dose escalation study will be evaluated using descriptive statistics: no sample size calculation was performed

Primary objectives

1. To identify the Maximum Tolerated Dose (MTD) and assess Safety and Tolerability of i.v. infused 131I-Tenatumomab.
2. To identify the optimal amount of unlabeled Tenatumomab able to convey 131I- Tenatumomab with the highest Tumor/nonTumor ratio.
3. To evaluate the whole body Dosimetry (safety dosimetry) and Tumor to normal tissue ratio (T/nT ratio, referred to AUC) of i.v.infused 131I-Tenatumomab.
4. To evaluate intra-lesional distribution and retention of 131I-Tenatumomab and to record individual lesion dosimetry.
5. To evaluate systemic biodistribution, pharmacokinetics, urinary excretion and dose linearity of 131I-Tenatumomab.

Secondary objectives

1. To evaluate proportional 131I-Tenatumomab tumor binding, as a function of the total load.
2. To evaluate Pharmacokinetics of Tenatumomab (protein and protein related materials) in serum.
3. To evaluate preliminary Efficacy of 131I-Tenatumomab based on disease response rate (Complete Response, Partial Response, Stable Disease) and patient's general clinical condition by ECOG performance status assessment.