Zelenectide pevedotin (BT8009) is Bicycle Therapeutics' lead Nectin-4-targeting bicyclic peptide-MMAE conjugate. The drug pairs a small synthetic bicyclic peptide that binds Nectin-4 — the same antigen targeted by enfortumab vedotin (Padcev) — with monomethyl auristatin E via a cleavable linker. The bicyclic peptide format gives different tissue-distribution and toxicity properties than the antibody-drug-conjugate competitor, with potentially better penetration into solid tumor cores.
The May 21, 2026 ASCO embargo lift produced two readouts. Phase 1 Duravelo-1 expansion in first-line cisplatin-ineligible metastatic urothelial cancer (22 patients on the 5 mg/m² + pembrolizumab combination) hit 65% ORR (13/20 evaluable) with 11.1-month median DOR in the monotherapy arm. Phase 2 Duravelo-2 detailed data released May 22 produced 65% ORR (17/26) regardless of confirmation, 58% BICR-confirmed ORR (15/26) at 27-week cutoff in 1L locally advanced or metastatic urothelial carcinoma combination cohort. The Phase 3 expansion moves forward at the optimal dose with high treatment retention and limited dose-limiting adverse events.
Stories here cover Duravelo trial data, the broader Bicycle bicyclic peptide pipeline (BT5528 EphA2, BT7480 EpCAM, nuzefatide pevedotin), and the urothelial cancer treatment landscape. See #bicycle-therapeutics, #duravelo-2, 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.