Breakthrough Clinical Results
Bicycle Therapeutics announced the presentation of two abstracts at the 2025 ASCO Annual Meeting, showcasing preliminary results from their Phase 1/2 Duravelo-1 and Phase 2/3 Duravelo-2 clinical trials. Both trials investigated zelenectide pevedotin (BT8009), a Bicycle® Drug Conjugate (BDC®) targeting Nectin-4, in patients with locally advanced or metastatic urothelial cancer. The Duravelo-1 study, a Phase 1/2 trial, evaluated zelenectide pevedotin in combination with pembrolizumab in previously untreated, cisplatin-ineligible patients. The Duravelo-2 study is a Phase 2/3 trial assessing zelenectide pevedotin as a monotherapy. The posters detailing these results will be available on the Bicycle Therapeutics website.
Key Highlights
- Presentation of two abstracts at the 2025 ASCO Annual Meeting.
- Preliminary results from Phase 1/2 Duravelo-1 and Phase 2/3 Duravelo-2 trials of zelenectide pevedotin (BT8009).
- Zelenectide pevedotin targets Nectin-4 in patients with locally advanced or metastatic urothelial cancer.
- Duravelo-1 trial evaluated BT8009 in combination with pembrolizumab, while Duravelo-2 assessed BT8009 as a monotherapy.
Latest Estimates of Urothelial Cancer Incidence and Prevalence
Based on available regional data:
Upper Tract Urothelial Cancer (UTUC)
- In Norway (1999-2018), the overall age-standardized incidence rate of UTUC was 3.88 per 100,000
- This rate showed an increase from 3.21 to 4.70 from the first to last 5-year periods
- UTUC constituted 11.8% of all urothelial cancers in Norway, increasing from 9.9% to 12.8% over the study period
United States Data
- Upper tract urothelial cancers represent an estimated 5%-10% of all urothelial cancers in the United States
- Approximately 3,000 new cases occur per year in the US
- The National Cancer Institute Surveillance, Epidemiology and End Results program (1973-1996) showed an increase in ureteral neoplasms from 0.69 to 0.73/100,000 person-years
Key Trial Parameters and Endpoints in Urothelial Cancer Studies
IMvigor 210 and CheckMate 275
These clinical trials were used to identify molecular features associated with PD-1/PD-L1 blockade resistance in metastatic urothelial cancer. The study identified an adaptive immune response gene signature associated with response and a protumorigenic inflammation gene signature associated with resistance to PD-1/PD-L1 blockade. The 2IR score (adaptive immune response:protumorigenic inflammation signature expression ratio) best correlated with clinical outcomes.
KEYNOTE-012
This phase 1b basket trial assessed pembrolizumab in locally advanced/metastatic urothelial cancer with the following design parameters: - Non-randomized, multi-cohort, open-label trial - Enrolled patients with ≥1% PD-L1 expression on tumor cells or stroma - Treatment: 10 mg/kg pembrolizumab every 2 weeks - Primary endpoints: safety and overall response (RECIST v1.1) - Results showed 26% overall response rate (11% complete, 15% partial responses)
Neoadjuvant vs. Adjuvant Chemotherapy Phase III Trial
This trial compared neoadjuvant vs. adjuvant chemotherapy with: - 140 patients randomized to either:
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Neoadjuvant M-VAC (2 courses) followed by surgery plus 3 additional cycles, or
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Initial cystectomy followed by 5 cycles of adjuvant chemotherapy
- Results showed no significant differences between groups
- 58% remained disease-free with median follow-up of 6.8 years
Gefitinib with First-line Chemotherapy Phase II Trial
This study evaluated gefitinib with first-line chemotherapy: - Randomized 1:1:1 to:
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Chemotherapy with concomitant gefitinib
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Sequential gefitinib
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Chemotherapy alone
- Primary endpoint: time to progression (TTP)
- Results: Median TTP for the three arms were 6.1, 6.3, and 7.8 months respectively
- No significant differences between treatment arms
TAR-200-101 Phase I Trial
This trial evaluated TAR-200 (intravesical gemcitabine delivery system): - Open-label study across 6 US and European sites - Eligible patients: T2a-T3b N0-N1 M0 urothelial cancer, ineligible/refused cisplatin - Two arms:
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Arm 1: residual tumor >3 cm after TURBT
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Arm 2: maximal TURBT, residual <3 cm
- Treatment: two 7-day cycles before radical cystectomy
- Primary outcome: safety
- Secondary outcomes: tolerability, pharmacokinetics, efficacy
Drug used in other indications
The context provided does not contain any information about zelenectide pevedotin, its clinical trials, or intervention models for any trials involving this drug. The context only mentions other treatments for urothelial cancer, including enfortumab vedotin, sacituzumab govitecan, RC48, erdafitinib, pembrolizumab, atezolizumab, avelumab, nivolumab, mocetinostat, docetaxel, and gemcitabine.
