Treatment of metastatic colorectal cancer with aimpila, a glycoside/alpha-fetoprotein complex

Abstract

3589 Background: Aimpila is a non-covalent complex of two natural compounds: porcine alpha-fetoprotein (PAFP) and a glycosidic apoptosis inducer (AI). PAFP is able to bind selectively to the AFP receptor-positive cancer cells and deliver the AI intracellularly due to AFP receptor-mediated endocytosis. The AI opens mitochondrial permeability transition pores, resulting in apoptosis. Preclinically, the complex is cytotoxic. We investigated the single agent activity of aimpila in patients (pts) with liver metastatic colorectal cancer (mCRC). Methods: Eligibility Criteria: Age >18 yrs, mCRC, any prior treatment, having documented progressive metastatic liver disease. Treatment consisted of oral capsules at a fixed sub-maximal dose (0.3 mg of active substance in an oral capsule, twice a day for 8 weeks). 12 pts were accrued, 6 chemonaïve; median ECOG performance status was 0, median age 56 years (range 45–65), and median time from previous treatment failure was 9.0 months (range 1–20). CT scans were performed before and after. Results: Of the 12 patients, 9 are evaluable for response by RECIST. Two achieved a complete response (CR), 1 a partial response (PR); subsequent confirmatory CT scans are pending. Three achieved stabilization (SD), in 2 cases = 2 months; 3 experienced disease progression. Of 3 non-evaluable pts, 1 experienced clinical deterioration without a CT scan, 1 experienced stable disease >2 months but with both lesions <10 mm in diameter, and a third developed nausea and vomiting leading to interruption of treatment, the only recorded significant adverse event. CEA estimations before and after treatment are available from 2 pts; 1 pt (radiological CR) going from 816 ng/ml to 268 ng/ml; the other (radiological SD) going from 1,243 ng/ml to 638 ng/ml. In this latter patient, one of the liver lesions disappeared, radiologically. The PR pt and 1 of the SD pts had progressed after previous oxaliplatin-based chemotherapy. Median survival has not yet been reached, with a median follow-up of 4 months. Conclusion: Single agent aimpila was well-tolerated in this patient population and produced major objective responses in some patients with liver mCRC. Further study is warranted. [Table: see text]