Bicycle Therapeutics Announces Pipeline Progress Update - Seite 2
- At doses of between 9.6 mg/m2 and 32.0 mg/m2 administered once-weekly, 13 out of 24 response evaluable patients at the eight week timepoint exhibited best response of at least stable disease. Ten of these 13 patients had a greater than 10% reduction in at least one target lesion, including a tumor reduction of 68% observed in one patient, a reduction that meets the RECIST Version 1.1 criteria of a partial response.
BT5528, a BTC targeting EphA2, a target for which prior antibody-based approaches have been unsuccessful, is currently being administered at doses within the predicted therapeutic range, with preliminary signs of anti-tumor activity
- Doses of BT5528 administered to date appear well-tolerated in the ongoing Phase I portion of the Phase I/II trial. BT5528 has been tolerated up to 8.5mg/m2 weekly, which Bicycle believes, based on pre-clinical studies, is toward the top of the therapeutic range, with transient neutropenia observed at that dose. Dose finding for the Phase II portion of the trial remains ongoing and additional weekly and every other week doses are currently being explored. Currently administered doses are in the predicted therapeutic range, delivering over 15-fold more toxin than MedImmune’s EphA2 antibody-drug conjugate (ADC) MEDI-547. In addition, and in contrast to the toxicities observed with MEDI-547, no signs of coagulopathy have been observed to date.
- Clinical PK profile of BT5528 is consistent with preclinical predictions. Early data received from tumor biopsies reveal that 24 hours after infusion of BT5528, tumor levels of the MMAE cytotoxin payload are approximately 10-fold greater than the corresponding plasma levels. Emerging, qualitative metabolite identification data from the clinical trial supports the hypothesis that BTCs undergo reduced hepatic metabolism and are eliminated renally.
Preliminary signs of anti-tumor activity have been observed. Although dosing continues to be refined, Bicycle has observed preliminary findings consistent with anti-tumor activity. An
EphA2 immunohistochemistry (IHC) assay was deployed during 2020, enabling pre-selection of patients in the Phase I portion of the trial. Since implementation of the IHC assay, patients are
prospectively screened and are eligible for enrollment based on a prespecified H-score. To date, two EphA2 selected patients have enrolled in the trial, one of whom was response evaluable.