Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new class of therapeutics based on its proprietary bicyclic peptide (Bicycles®) product platform, today 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. The results are being presented by Natalie Cook, Ph.D., a study investigator and Senior Clinical Lecturer at the University of Manchester, today from 12:00-13:00 CET in a poster session at the European Society of Medical Oncology (ESMO) 2019 Annual Congress in Barcelona, Spain. The poster is available on the Publications section of bicycletherapeutics.com.
“The data being presented at ESMO demonstrate encouraging progress of the dose escalation portion of the Phase I/IIa trial evaluating BT1718,” said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. “We believe these early data underscore the potential of Bicycles as a novel therapeutic modality and plan to provide additional updates from across our pipeline at medical meetings through the rest of this year.”
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 (54%) 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.
Across all dose levels and schedules tested, the most common treatment-related adverse events (>15%, n=28) were anemia, diarrhea, nausea, vomiting, fatigue, alanine aminotransferase increase, aspartate aminotransferase increase, blood alkaline phosphatase increase, gamma-glutamyltransferase increase, decreased appetite, lethargy and peripheral neuropathy.
Evaluation of pharmacokinetics demonstrated that BT1718 area under the curve (AUC) was approximately dose proportional over the range 0.6-25 mg/m2, and cycle 2 values were consistent with cycle 1. Mean (±SD) plasma clearance (CLp) was 33.6 (±24.5) L/h, with mean (±SD) volume of distribution (Vss) of 12.5 (±7.3) L, resulting in a terminal half-life (t1/2) 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.
“We are on track to achieve the primary objectives of the Phase I portion of the study,” said Udai Banerji, M.D., Ph.D, chief investigator of the study and Deputy Director of the Drug Development Unit at The Institute of Cancer Research, London and The Royal Marsden NHS Foundation Trust. “BT1718 represents an exciting potential first-in-class drug, which appears tolerable in Phase I evaluation. Importantly, in two patient biopsies, we observed presence of cytotoxic payload to tumors consistent with targeted delivery and in a manner predicted by our preclinical models.”
Nigel Blackburn, Ph.D., Cancer Research UK's Director of Drug Development, said: “Based on our experience, these early clinical data are very promising and a testament to our strong partnership with Bicycle Therapeutics. We are pleased to help accelerate potentially groundbreaking new therapeutics such as BT1718 into clinical trials. This is an excellent example of the innovative work our Centre of Drug Development can support and is an important step toward helping more people survive cancer."
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 (RP2D) 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.
Article sourced from https://www.businesswire.com/news/home/20190928005007/en/
Published on: 28.09.2019
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