Bicycle Therapeutics plc (NASDAQ: BCYC) announced updated Phase 1/2 clinical results for its oncology pipeline at the European Society for Medical Oncology (ESMO) Congress 2024 in Barcelona. The data highlight the potential of Bicycle Therapeutics' bicyclic peptide technology to create differentiated medicines for underserved diseases.
Zelenectide Pevedotin Shows Promise in Metastatic Urothelial Cancer
Zelenectide pevedotin, a Bicycle Toxin Conjugate (BTC) targeting Nectin-4, demonstrated a 45% overall response rate (ORR) in metastatic urothelial cancer (mUC) patients who had not previously been treated with enfortumab vedotin. The data comes from the ongoing Phase 1/2 Duravelo-1 trial evaluating 5 mg/m2 weekly of zelenectide pevedotin monotherapy in 38 efficacy-evaluable patients. The median duration of response was 11.1 months among the 14 patients with confirmed responses. Notably, the treatment showed an emerging differentiated safety profile, with no Grade ≥3 treatment-related adverse events (TRAEs) of peripheral neuropathy, skin reactions, or eye disorders.
The global Phase 2/3 Duravelo-2 registrational trial of zelenectide pevedotin in patients with mUC is currently enrolling. Additional data updates for zelenectide pevedotin in combination with pembrolizumab in first-line mUC and monotherapy in late-line triple-negative breast cancer and non-small cell lung cancer (NSCLC) are planned for later this year.
BT5528 Demonstrates Antitumor Activity in Advanced Solid Tumors
BT5528, a BTC molecule targeting EphA2, showed antitumor activity in patients with advanced solid tumors. In the dose expansion cohort of mUC patients receiving 6.5 mg/m2 every two weeks, a 45% ORR was observed. Across all efficacy-evaluable patients, a 12% ORR was observed in patients with advanced solid tumors. The trial also suggested a correlation between EphA2 expression and response, with a 43% ORR in EphA2-positive mUC patients compared to a 20% ORR in EphA2-negative patients.
The company has begun assessing BT5528 at 6.5 mg/m2 every two weeks in combination with nivolumab, with results expected in 2025.
Low Rates of Peripheral Neuropathy with Bicycle Toxin Conjugates
An analysis of 149 patients treated with zelenectide pevedotin and 74 patients treated with BT5528 showed low rates of treatment-related peripheral neuropathy (TRPN). TRPN occurred in 28% of patients treated with zelenectide pevedotin and 19% of patients treated with BT5528, nearly all of which were low grade (1-2). The data suggest that the antibody-drug construct may be a primary driver of peripheral neuropathy rather than MMAE toxicity.
BT7480 Shows Favorable Safety Profile in Advanced Solid Tumors
BT7480, a Nectin-4 targeted CD137 agonist, demonstrated a favorable safety profile and preliminary antitumor activity in advanced solid tumors. Initial data from the Phase 1/2 dose escalation trial showed low rates of Grade ≥3 TRAEs (5%) and treatment-related severe adverse events (TRSAEs) (8%). The best overall response was stable disease in 13 patients. The company is continuing dose exploration in combination studies, starting with nivolumab, as the maximum tolerated dose for BT7480 has not yet been reached.
