An open label phase I study of ABR-217620, a fusion protein of the 5T4 antibody moiety and an engineered superantigen, in patients with non-small cell lung, renal cell or pancreatic cancer.

3083 Background: ABR-217620 (naptumomab estafenatox) is a recombinant fusion protein that consists of the 5T4Fab moiety genetically fused to the engineered superantigen variant SEA/E-120. This fusion protein is a new generation tumor-targeted superantigen based on the previously described ABR-214936 (anatumomab mafenatox). ABR-217620 was designed to reduce antigenicity and toxicity. The 5T4 antigen is expressed on more than 95 % of tumors from patients with non-small cell lung (NSCLC), renal cell (RCC) and pancreatic cancer (PC). In clinical PET studies 124I-labeled ABR-217620 has been shown to localize to 5T4 positive tumors. METHODS The compound was administered as a 5 min bolus infusion for 5 consecutive days. Patients with disease control at day 28 were offered a second cycle of therapy. Dose escalation has been performed using a Bayesian model starting at 0.5 μg/kg/day. The primary endpoint is determination of MTD. Secondary endpoints include characterization of side effects, immunological response, efficacy and pharmacokinetics. RESULTS 31 patients to date have been treated (19 NSCLC, 8 RCC, 4 PC). 3 patients have had dose limiting toxicities (fever, hypotension and nausea, grade 3) at doses between 23 and 28 μg/kg/day. The side effects were resolved quickly. Based on the experience from ABR-214936, these side effects were expected, but the MTD is ∼ 200 times higher. ABR-217620 leads to a dose dependent systemic increase of cytokines including IL-2 and IFN-γ after infusion. It also leads to an expansion of the superantigen reactive T cell population. 16/29 evaluable patients investigated had SD while 13 patients had PD. In contrast to ABR-214936, the first cycle of ABR-217620 treatment can be given without factoring in the titer of preformed anti-superantigen antibodies. CONCLUSIONS ABR-217620 treatment had predicted and manageable side effects with fever, hypotension and nausea being dose limiting toxicities. Treatment with ABR-217620 resulted in a restricted systemic activation of the immune system. A large fraction of the patients have had stable disease. [Table: see text].