Phase I study and preliminary pharmacology of the novel innate immune modulator rBBX-01 in gynecologic cancers.

PURPOSE: A recombinant protein product, rBBX-01, is the first innate immunostimulator derived from a protozoan (Eimeria protozoan) and has shown potent preclinical in vivo and in vitro activities. This phase I trial was done to determine the safety and basic pharmacology of rBBX-01. EXPERIMENTAL DESIGN: Eligible patients had recurrent incurable gynecologic malignancies. The study was divided into three components: a starting low-dose phase (0.85, 2.0, and 4.0 microg/m2), an intrapatient dose acceleration phase (4.0-1,024.0 microg/m2), and a high-dose phase (1,000 and 2,000 microg/m2). All treatment doses were administered daily for 5 days. Patients were allowed a second cycle of treatment if there was evidence of response. RESULTS: Sixteen patients received a total of 20 cycles of rBBX-01. All patients tolerated the drug well, exhibiting no local or systemic, acute or delayed, adverse reactions. Plasma levels of rBBX-01 were detectable in all patients over the entire dose range, although changes in the pharmacodynamic marker (interleukin-12) exhibited patient-to-patient variability. Of 14 patients with ovarian, primary peritoneal, or endometrial cancer with elevated CA125 biomarkers at the start of treatment, 4 responded with decreased levels of CA125. One patient showed decreasing CA125 levels for 10 months and received no additional chemotherapy for 11 months. Those patients exhibiting reductions in CA125 also exhibited increased levels of plasma interleukin-12 during the week of therapy. CONCLUSION: The immunostimulator rBBX-01 was safe in multidose regimens in heavily pretreated women. Of the 14 patients with elevated CA125 levels, an approximately 30% response rate was detected. rBBX-01 should receive additional testing in the clinical setting.