Phase I Safety and Biodistribution Study of ¹²⁴I-PEG-AVP0458 Diabody in Patients with TAG-72 Positive Ovarian and Prostate Cancer

Objectives The use of small molecular weight antibody constructs (eg diabodies) has great promise for antibody therapeutics. We have developed a novel pegylated diabody to TAG-72 (AVP0458) for a Phase I, open label, first-in-human trial of PEG-AVP0458.

Methods The primary study objective was the safety of single dose of ¹²⁴I-PEG-AVP0458 in patients (pts) with TAG-72 +ve relapsed / metastatic prostate or ovarian cancer. Secondary study objectives were evaluation of the biodistribution, tumor targeting, pharmacokinetics (PK) and immunogenicity of ¹²⁴I-PEG-AVP0458. Pts were infused with ¹²⁴I-PEG-AVP0458 (3-5mCi) at one of two dose levels (1mg/m² and 10mg/m²), and imaged over a one week period, with assessment of safety, PK, and immunogenicity.

Results Six pts (1F:5M; age range 62-85yrs; 1 ovarian cancer, 5 prostate cancer) were entered into the study, 3 at each dose level. ¹²⁴I-PEG-AVP0458 was well tolerated, with no infusion-related or serious adverse events observed. There was consistent biodistribution on PET imaging of ¹²⁴I-PEG-AVP0458, with no normal tissue uptake. High tumor uptake was evident in metastatic disease in liver and lymph nodes, with lesion uptake seen within 1-2 days post infusion. PK analysis showed a T½Β of 46.8 ± 12.4 hrs. There was no impact of protein dose on biodistribution, tumor uptake or PK. No immunogenicity to PEG-AVP0458 was evident.

Conclusions ¹²⁴I-PEG-AVP0458 is safe, and demonstrates excellent, rapid targeting of tumor in-vivo, with no normal organ uptake, and high tumor: blood ratios. This data demonstrates the feasibility of using pegylated diabodies for imaging and for payload delivery of radionuclides or cytotoxic drugs in cancer patients.

Research Support This work was supported by Avipep Pty Ltd.