Therapy Areas: Respiratory
Bicycle Therapeutics Posts BT5528 Phase I Dose Escalation Results in Patients with Advanced Solid Tumors
8 September 2022 - - UK-based biotechnology company Bicycle Therapeutics plc (NASDAQ: BCYC) has posted Phase I dose escalation top-line results from its Phase I/II trial of BT5528, a BTC targeting EphA2, in patients with advanced solid tumors, the company said.

BT5528, a BTC targeting EphA2, a target for which prior antibody-based approaches have been unsuccessful, has demonstrated anti-tumor activity and differentiated tolerability.

Bicycle has established an RP2D dose (6.5mg/m2 every other week) and is enrolling ongoing expansion cohorts.

Preliminary signs of anti-tumor activity observed. A total of 45 patients (15 at RP2D 6.5mg/m2 every other week) were dosed with a median of four prior lines of therapy. Expression of EphA2 was evaluated retrospectively using an immunohistochemistry assay.

Amongst these patients, anti-tumor activity was observed in urothelial and ovarian cancer patients.

A total of 21 ovarian cancer patients were dosed. Of these, nine response evaluable patients were determined to be EphA2-positive based on the IHC assay. The median prior lines of therapy for these nine patients was four.

Among these nine late-line ovarian cancer patients, six patients were observed to have a reduction in target lesions, including one patient with a complete response and one with a partial response under Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, resulting in a disease control rate of 67% and an overall response rate of 22%.

A total of eight urothelial patients were dosed. Of these, three response evaluable patients were determined to be EphA2-positive based on the IHC assay and of these three patients, two were observed to have tumor reductions constituting a PR under RECIST version 1.1 (ORR and DCR of 67%).

BT5528 well-tolerated at RP2D of 6.5mg/m2 every other week. Low, or no, levels of incidence of neutrophil count decrease, peripheral neuropathy, skin rash and eye disorders were reported. Low-grade GI treatment-related events were those most commonly reported amongst the 15 patients at this dose.

There were three Grade 3 and above events at the RP2D: diarrhea (n=1, 7%) and anemia (n=2, 13%).

In addition, and in contrast to the toxicities observed with EphA2 ADCs, Bicycle has observed no signs of treatment-related coagulopathy to date in any patient.

Bicycle advancing BT5528 in ongoing expansion cohorts. In June 2022, Bicycle announced the dosing of the first patient in the part B dose expansion portion of the Phase I/II trial. Up to 56 patients will be enrolled in the initial expansion cohorts, with the ability to further expand enrollment based on results from these cohorts.

Dose expansion is taking place in urothelial and ovarian cancers as well as in a basket cohort of other solid tumors, including non-small cell lung, triple-negative breast, head and neck, and esophageal cancers.

Bicycle Therapeutics (NASDAQ: BCYC) is a clinical-stage biopharmaceutical company developing a novel class of medicines, referred to as Bicycles, for diseases that are underserved by existing therapeutics.

Bicycles are fully synthetic short peptides constrained with small molecule scaffolds to form two loops that stabilize their structural geometry.

This constraint facilitates target binding with high affinity and selectivity, making Bicycles attractive candidates for drug development.

Bicycle is evaluating BT5528, a second-generation Bicycle Toxin Conjugate targeting EphA2; BT8009, a second-generation BTC targeting Nectin-4, a well-validated tumor antigen; and BT7480, a Bicycle TICA targeting Nectin-4 and agonizing CD137, in company-sponsored Phase I/II trials.

In addition, BT1718, a BTC that targets MT1-MMP, is being investigated in an ongoing Phase I/IIa clinical trial sponsored by the Cancer Research UK Centre for Drug Development.

Bicycle is headquartered in Cambridge, UK, with many key functions and members of its leadership team located in Lexington, Massachusetts.
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