Bicycle Therapeutics reports early Phase 2 Duravelo‑2 data for zelenectide pevedotin in metastatic urothelial cancer, showing response rates comparable to SOC with markedly lower neuropathy and skin toxicity. Findings to be presented at ASCO 2026.
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
Bicycle Therapeutics reported initial randomized Phase 2 Duravelo 2 data (NCT06225596) showing that zelenectide pevedotin (BT8009) produced response rates comparable to current standards of care in metastatic urothelial cancer while demonstrating lower rates of neuropathy and skin toxicity. The results will be presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, with both oral and poster sessions led by investigators Yohann Loriot and Dan Petrylak.
Frontline Combination Outcomes
In previously untreated mUC patients receiving zelenectide plus pembrolizumab at the optimal 6 mg dose, the trial reported a 65% overall response rate (ORR) by investigator assessment. Blinded independent central review confirmed a 58% ORR at the 27‑week cutoff, rising to 62% with one additional confirmed response after cutoff. Median progression‑free survival (PFS) remains immature at this stage.
Monotherapy in Previously Treated Patients
Among patients with prior therapy, zelenectide monotherapy achieved a 37% ORR, including 11% complete responses. Median duration of response was approximately 10 months, with safety findings consistent across cohorts.
Phase 1 Duravelo‑1 Update
Updated Phase 1 data (NCT04561362) further supported the program. In cisplatin‑ineligible frontline patients treated with zelenectide plus pembrolizumab, ORR reached 59%, with median PFS comparable to published standard of care data. In enfortumab vedotin‑naïve recurrent mUC patients receiving monotherapy, confirmed ORR was 32%, with median duration of response of 10 months.
Safety and Differentiation
Current “Nectin‑4” targeted standards of care in metastatic urothelial cancer are associated with substantial neuropathy and dermatologic toxicity, often leading to dose reductions or treatment discontinuation.
The combination arm reported peripheral neuropathy in 33%, skin reactions in 17%, and eye disorders in 10% of patients. Importantly, no Grade 4/5 treatment‑related adverse events, severe skin reactions, or zelenectide‑related hyperglycemia were observed. Only one patient discontinued due to a zelenectide‑related adverse event. Compared with published SOC data, zelenectide demonstrated four‑fold lower rates of skin reactions and approximately half the incidence of neuropathy, underscoring its differentiated tolerability profile.
Platform and Company Commentary
Zelenectide pevedotin is a Bicycle Drug Conjugate (BDC) targeting Nectin‑4, a validated antigen highly expressed in urothelial tumors. Unlike antibody‑drug conjugates, Bicycle molecules employ synthetic bicyclic peptides that may improve tumor penetration and reduce off target toxicity.
Chief Executive Officer Kevin Lee emphasized that across more than 600 patients treated, the growing dataset consistently supports the differentiated tolerability of Bicycle molecules compared with antibody‑based therapies. The company plans to release additional randomized Duravelo‑2 data in the second half of 2026.
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About the Writer
Nikita Jha, BPharm (LinkedIn) a pharmacy graduate specializing in medical writing, with a strong ability to interpret complex medical and regulatory information and translate it into clear, accurate, and evidence-based healthcare content. Known for her attention to detail and precision, she focuses on delivering high-quality scientific communication that supports drug safety and informed decision-making.