Duravelo-2 is Bicycle Therapeutics' Phase 2/3 trial of zelenectide pevedotin (BT8009) plus pembrolizumab as first-line treatment in patients with previously untreated locally advanced or metastatic urothelial carcinoma. Zelenectide pevedotin is a Bicycle toxin conjugate — a Nectin-4-targeting bicyclic peptide linked to the cytotoxin monomethyl auristatin E (MMAE) via a cleavable linker. The drug targets the same antigen as enfortumab vedotin (Padcev) but as a small bicyclic peptide rather than an antibody-drug conjugate, giving it a different tissue-distribution and toxicity profile.
Bicycle confirmed the ASCO 2026 oral presentation slot in April 2026 (Abstract 4516, Monday June 1, 8:30-8:36 AM CT in the GU Cancers track). Interim analysis data released with the May 21 ASCO embargo lift set up the Phase 3 expansion decision, and the June 1 rapid oral presentation (Abstract 4516, Yohann Loriot) reported that the optimal dose of zelenectide pevedotin plus pembrolizumab matched published standard-of-care response rates with roughly four-fold lower skin reactions and about half the peripheral neuropathy. The Phase 1 Duravelo-1 monotherapy expansion in cisplatin-ineligible 1L mUC delivered a 45% ORR with 11.1-month median DOR; the Duravelo-1 combination arm with pembrolizumab in 22 patients delivered a 65% ORR (13/20 evaluable).
Stories here cover Duravelo-2 interim data, the broader Bicycle Therapeutics Nectin-4 pipeline (including BT5528 EphA2 conjugate), and the urothelial carcinoma treatment landscape. See #bicycle-therapeutics, #zelenectide-pevedotin, and #urothelial-cancer for adjacent threads.
In the June 1 rapid oral session (Abstract 4516, Yohann Loriot), the dose-optimization stage of the randomized Phase 2 Duravelo-2 trial showed the optimal dose of the bicyclic peptide-drug conjugate zelenectide pevedotin (BT8009) plus pembrolizumab produced response rates comparable to published standard-of-care data in previously untreated locally advanced or metastatic urothelial carcinoma, with roughly four-fold lower skin reactions and about half the peripheral neuropathy. The separate Duravelo-1 Phase 1 trial showed median progression-free survival comparable to standard of care in cisplatin-ineligible patients.
Bicycle Therapeutics' formal post-ASCO 2026 press release Friday morning specified the headline Phase 2 numbers from yesterday's abstract release. In the Duravelo-2 combination cohort, the optimal zelenectide dose plus pembrolizumab 200 mg every three weeks produced 65% ORR (17/26 evaluable patients) regardless of confirmation, with 58% BICR-confirmed ORR (15/26) at the 27-week cutoff in previously untreated locally advanced or metastatic urothelial cancer. An additional confirmed BICR response observed after the cutoff would bring the rate to 62%. The trial tested two dose schedules: 5 mg/m² weekly and 6 mg/m² two-weeks-on-one-week-off; the optimal dose moves forward in the Phase 3 expansion. Treatment retention was high and dose-limiting adverse events limited. The 65% Phase 2 ORR matches the 65% Phase 1 Duravelo-1 ORR (13/20) — pharmacology consistency across two different patient populations, an unusual durability signal for a peptide-drug conjugate.
Bicycle Therapeutics released Duravelo-2 Phase 2/3 interim analysis data at ASCO 2026 — zelenectide pevedotin (BT8009, a Nectin-4-targeting bicyclic peptide-MMAE conjugate) plus pembrolizumab in previously untreated locally advanced or metastatic urothelial cancer. The full data presentation is scheduled for Monday June 1, 8:30-8:36 AM CT in the GU Cancers oral session (Abstract 4516). The Duravelo-1 monotherapy comparator anchor — 65% ORR (13/20) in cisplatin-ineligible 1L mUC at 5 mg/m² + pembrolizumab combination, with median DOR 11.1 months in the monotherapy expansion — sets the bar for what the Duravelo-2 combination interim must clear. Bicycle's five-abstract ASCO package includes the oral Duravelo-2 piece plus four posters covering Duravelo-1 monotherapy update, BT5528 EphA2 monotherapy and combination cohorts, and BT8009 second-line urothelial data.
Bicycle Therapeutics confirmed the Duravelo-2 oral abstract presentation slot at the ASCO 2026 Annual Meeting on Monday, June 1, 8:30–8:36 a.m. CT. The abstract reports interim analysis results from Duravelo-2, a Phase 2/3 trial of zelenectide pevedotin (BT8009) plus pembrolizumab as first-line treatment for previously untreated locally advanced or metastatic urothelial carcinoma. Zelenectide pevedotin is Bicycle's Nectin-4-targeting bicyclic peptide-drug conjugate, a separate program from the EphA2-targeting nuzefatide pevedotin (BT5528) covered earlier on this site. The Q1 2026 print (April 30) reaffirmed $559.5M cash and runway to 2030 supporting the Phase 3 expansion of the platform.
Bicycle Therapeutics reported Q1 2026 financial results April 30 — net loss of $60.8M ($0.87 per share) on R&D of approximately $44M, with $559.5M in cash and equivalents at March 31 supporting a cash runway into 2030. The pipeline update reaffirmed that nuzefatide pevedotin (BT5528) Duravelo-2 dose-selection data in EphA2-positive solid tumors will be presented at the ASCO 2026 Rapid Oral Abstract Session on June 1, the Phase 2 nuzefatide pevedotin trial in recurrent pancreatic cancer enrolled its first patient in April, and the EphA2 gallium-68 PET imaging program continues to accumulate first-in-human data. Bicycle remains the leading bicyclic-peptide-platform pure-play in oncology.