Bicycle Therapeutics presents data from Phase I/IIa trial evaluating BT1718
Bicycle Therapeutics announced the presentation of updated data from a Phase I/IIa trial conducted in collaboration with Cancer Research UK and evaluating BT1718 in an unselected group of patients with advanced solid tumors. Patients in the Phase I dose escalation were assessed for anti-tumor activity, safety and pharmacokinetics up to the data cutoff of August 7, 2019. Based on data from patients in cohorts across dose levels tested, many of which are below the predicted therapeutic range, 13 of 24 evaluable patients had stable disease at the eight-week timepoint, including a patient who experienced a 45% reduction in a target lesion. With once-weekly dosing, which is the expected schedule for the Phase IIa portion of the study, BT1718 has appeared tolerable, with manageable adverse events. The Phase I once-weekly dose escalation portion of the trial is ongoing, with dosing at levels equivalent to those associated with preclinical responses. Evaluation of pharmacokinetics demonstrated that BT1718 area under the curve was approximately dose proportional over the range 0.6-25 mg/m2, and cycle 2 values were consistent with cycle 1. Mean plasma clearance was 33.6 L/h, with mean volume of distribution of 12.5 L, resulting in a terminal half-life of 0.2 to 0.5 hours. Two tumor biopsies were obtained from patients dosed at levels above 15 mg/m2 and analysis showed delivery of DM1 to the tumor consistent with preclinical models. These findings suggest rapid tumor penetration by BT1718. Further plasma and tumor DM1 analysis is ongoing to assess the extent of DM1 retention. The Phase I/IIa study of BT1718 is being sponsored by Cancer Research UK. The primary objectives of the Phase I dose escalation portion of the trial are to select the recommended Phase II dose by establishing the maximum tolerated dose and maximum administered dose, and to assess the safety and toxicity profile of BT1718 in patients with advanced solid tumors. Following selection of the once-weekly RP2D, the Phase IIa portion of the study, consisting of up to four cohorts in selected indications in which MT1-MMP is expressed, will be initiated.