Announcement • May 24
Bicycle Therapeutics plc Presents Initial Duravelo-2 Data At 2026 Asco Annual Meeting
Bicycle Therapeutics plc announced the presentation of initial data from the randomized Phase 2 trial (Duravelo-2) evaluating zelenectide pevedotin (zelenectide) in previously untreated patients with metastatic urothelial cancer (mUC), demonstrating encouraging response rates and a potentially differentiated safety profile both as a monotherapy and in combination with pembrolizumab. Updated data from the Phase 1 trial (Duravelo-1) in previously untreated, cisplatin-ineligible mUC patients demonstrated encouraging median progression-free survival (PFS) comparable to published data for standard of care (SOC). In the dose optimization stage of the randomized Phase 2 trial (Duravelo-2), zelenectide pevedotin at its optimal dose in combination with pembrolizumab demonstrated response rates comparable to published data for standard of care (SOC) in patients with previously untreated metastatic urothelial cancer (mUC). The optimal dose of zelenectide demonstrated a potentially differentiated safety profile with incidence rates approximately four-fold lower for skin reactions and half that for peripheral neuropathy as published for SOC. Further data from the randomized Phase 2 trial are expected in Second Half 2026. In a separate Phase 1 trial (Duravelo-1) in previously untreated, cisplatin-ineligible mUC, zelenectide in combination with pembrolizumab demonstrated a clinically meaningful median progression-free survival comparable to published data for SOC. Zelenectide is a Bicycle Drug Conjugate (BDC) targeting Nectin-4, a well-validated tumor antigen. The Duravelo-2 trial evaluated two doses of zelenectide – 5mg/m2 weekly (5mg dose) and 6mg/m2 (6mg dose) two weeks on, one week off – in combination with 200mg of pembrolizumab once every three weeks in previously untreated patients with mUC (Cohort 1). Bicycle reached regulatory alignment on the zelenectide 6mg dose as optimal both in combination with pembrolizumab and as a monotherapy. Cohort 1 data were extracted for the interim analysis at Week 27, on July 23, 2025. At the time of the data cut, the median PFS was not mature, and the results at the optimal dose showed: 65% (17/26) overall response rate (ORR) regardless of confirmation and blinded independent central review (BICR) confirmed ORR of 58% (15/26) at the 27-week cutoff. Subsequent to the 27-week cutoff, an additional confirmed BICR response was observed, which would result in an ORR of 62% (16/26). Median duration of treatment (mDOT) was 6.3 months (0.7-10.6). 65% of patients remain on treatment. Median relative dose intensity in patients receiving the optimal dose was 97%. Low rates of zelenectide-related adverse events (AEs) of clinical interest were observed, including peripheral neuropathy, sensory (33%); skin reactions (17%); eye disorders (10%). There were no reported instances of zelenectide-related hyperglycemia. No zelenectide-related severe skin reactions of any grade were reported. The single Grade 3 zelenectide-related AE of clinical interest, peripheral neuropathy, resolved to Grade =1. There were no Grade 4 or Grade 5 zelenectide-related AEs of clinical interest. Only one patient at the optimal dose discontinued therapy due to a zelenectide-related AE at the time of the data cut in Cohort 1. The Duravelo-2 trial also evaluated the 5mg dose and 6mg dose regimens of zelenectide as a monotherapy in mUC patients with one or more prior lines of systemic therapy (Cohort 2). Cohort 2 data were extracted for the interim analysis at Week 27, on June 14, 2025. At the time of the data cut, the median PFS was not mature, and the results at the optimal dose showed: 37% (10/27) ORR regardless of confirmation and 30% confirmed ORR (8/27) was achieved among efficacy-evaluable patients. Of the confirmed responses, 3 (11%) were complete responses (CRs) and 5 (19%) were partial responses (PRs). mDOT was 4.8 months (1.3-10.1). 31% of patients remain on treatment. Median relative dose intensity in patients receiving the optimal dose was 86%. Low rates of zelenectide-related AEs of clinical interest were observed, including peripheral neuropathy (38%); skin reactions (28%); eye disorders (10%); and hyperglycemia (3%). There were no Grade 4 or Grade 5 zelenectide-related AEs of clinical interest. No zelenectide-related severe skin reactions of any grade were reported, and no treatment discontinuations occurred at the optimal dose. The company plans to share additional Duravelo-2 data from the randomized Phase 2 trial in the Second Half 2026. The company also announced the presentation of updated Phase 1 Duravelo-1 data evaluating zelenectide in mUC, including monotherapy data in enfortumab vedotin (EV)-naïve patients and in combination with 200mg of pembrolizumab once every three weeks in previously untreated cisplatin-ineligible patients. Both cohorts evaluated zelenectide at the 5mg dose. Updated results as of the August 1, 2025 data cutoff evaluating zelenectide in combination with pembrolizumab in previously untreated cisplatin-ineligible patients, 45% of whom were classified as Eastern Cooperative Oncology Group (ECOG) performance status of 2, showed: 59% (13/22) ORR regardless of confirmation, 50% confirmed ORR (11/22), and a disease control rate (DCR) of 82%. Of the confirmed responses, 5 (23%) were CRs and 6 (27%) were PRs. Median PFS was 13.0 months and median duration of response (mDOR) was not mature at the time of the data cutoff. Updated results as of the August 1, 2025 data cutoff evaluating zelenectide as a monotherapy in EV-naïve recurrent, unresectable mUC patients who had prior anti-programmed death-1/programmed death ligand-1 (PD-1/PD-L1), had disease progression after or were ineligible for platinum-based chemotherapy showed: 38% (20/53) ORR regardless of confirmation, 32% confirmed ORR (17/53) and a DCR of 66%. Of the confirmed responses, 2 (4%) were CRs and 15 (28%) were PRs. Median PFS was 5.4 months and mDOR was 10.0 months (5.3-16.6) among patients with confirmed responses. Across all patients, the safety and tolerability profile was consistent with other zelenectide data to date. No new safety signals were observed and there were no Grade 4 or Grade 5 zelenectide-related AEs of clinical interest reported.
