Bicycle Therapeutics announced updated topline Phase 1 combination data for zelenectide pevedotin plus pembrolizumab, demonstrating a 65% overall response rate (ORR) in first-line cisplatin-ineligible patients with metastatic urothelial cancer (mUC). The results, presented on January 13, 2025, highlight the potential of zelenectide pevedotin as a promising therapy for Nectin-4 expressing cancers.
The ongoing Phase 1 Duravelo-1 trial evaluated zelenectide pevedotin at 5 mg/m2 weekly plus pembrolizumab at 200 mg every three weeks in 22 patients. Key findings from the data cutoff on January 3, 2025, include a 65% ORR (13/20) among efficacy-evaluable patients and a 50% ORR (10/20) among patients with confirmed responses. The median duration of response (mDOR) is not yet mature, with 12 patients remaining on treatment.
Safety and Tolerability
The combination therapy demonstrated a favorable safety profile, consistent with previous zelenectide pevedotin monotherapy and combination cohorts. Adverse events of clinical interest, such as peripheral neuropathy, skin reactions, and eye disorders, were primarily low grade. All Grade 3 treatment-related adverse events (TRAEs) were reversible, and no Grade 4 or 5 TRAEs of clinical interest were reported. Importantly, no patients withdrew from the study due to zelenectide TRAEs.
Ongoing and Planned Clinical Trials
Bicycle Therapeutics is currently conducting the Phase 2/3 Duravelo-2 registrational trial, which is evaluating zelenectide pevedotin plus pembrolizumab versus chemotherapy in first-line mUC (Cohort 1), and zelenectide pevedotin monotherapy and in combination with pembrolizumab in late-line mUC (Cohort 2). The trial is assessing two doses of zelenectide pevedotin: 5 mg/m2 weekly and 6 mg/m2 two weeks on, one week off, before selecting a final dose.
In 2025, Bicycle Therapeutics plans to initiate Phase 1 trials in NECTIN4 gene-amplified breast cancer (Duravelo-3) in 1H 2025 and NECTIN4 gene-amplified lung cancer (Duravelo-4) and multi-tumor (Duravelo-5) in 2H 2025. These trials aim to expand the potential use of zelenectide pevedotin across multiple Nectin-4 associated cancers.
Radiopharmaceutical Pipeline
Bicycle Therapeutics is also advancing its emerging Bicycle Radionuclide Conjugates (BRC) pipeline. Additional MT1-MMP human imaging data is expected in mid-2025, with initial EphA2 human imaging data planned for 2H 2025. These efforts support the company's strategy to become a leader in next-generation radiopharmaceuticals.
Financial Position
As of September 30, 2024, Bicycle Therapeutics had $890.9 million in cash and cash equivalents, providing an expected financial runway into the second half of 2027. This financial stability supports the execution of the company's clinical and strategic priorities.
"We are encouraged by our updated topline Phase 1 combination data for zelenectide pevedotin plus pembrolizumab in first-line cisplatin-ineligible patients, which we believe continue to demonstrate a differentiated safety profile and encouraging response rates in patients with poor prognosis and limited treatment options," said CEO Kevin Lee, Ph.D.
