BT8009, a Nectin-4 targeted BTC, developed by Bicycle Therapeutics, represents a novel class of anti-cancer agents that combine the high specificity of small peptides with potent cytotoxic payloads.  The drug has lower molecular weight and shorter plasma half-life than antibody drug conjugates, with potential to rapidly penetrate tumors and minimize healthy tissue exposure.

The ongoing Phase I/II (NCT04561362) Duravelo-1 trial evaluating BT8009 as monotherapy in enfortumab vedotin-naive patients with metastatic urothelial carcinoma offers significant insights into the emerging role of Bicycle Toxin Conjugates in oncology. Updated results from BT8009 monotherapy at recommended Phase II dose of 5 mg/m2 weekly were presented at the ESMO 2024 conference.

Median time on treatment was 16.1 weeks. In 38 efficacy-evaluable patients, the best overall response rate was 45%, with one complete response (3%) and 16 partial responses (42%). Stable disease was observed in nine patients. The median duration of response for those with confirmed responses was 11.1 months. 

In term of safety, a total of 93% patients experienced any TEAEs. There were no Grade ≥3 treatment-related adverse events of neuropathy (any kind), skin reactions, or eye disorders. The pharmacokinetics of enfortumab vedotin-naive patients with metastatic urothelial carcinoma was consistent with pharmacokinetics observed across the entire study.

Conclusion 

Urothelial carcinoma is the most common form of bladder cancer, accounting for approximately 90% of cases, with approximately 86,000 incident cases in the US, in 2023, as per DelveInsight.

The ongoing Duravelo-1 study of BT8009 monotherapy at 5 mg/m2 weekly shows a promising response profile and a generally well-tolerated safety profile in patients with metastatic urothelial carcinoma, as presented at the ESMO 2024 conference, suggesting its potential as a first-line therapy in metastatic urothelial carcinoma, especially for cisplatin-ineligible patients. In addition to this Phase I/II Duravelo-1 trial, the company is also conducting a Phase II/III Duravelo-2 trial, evaluating BT8009 as a treatment for metastatic urothelial cancer. 

​In the Nectin-4 targeting space, BT7480 competes with PADCEV, the first ADC approved for Nectin-4-expressing bladder cancer. However, BT8009 offers superior tumor specificity, binding more precisely to cancer cells and reducing off-target effects. Bicycle Therapeutics’ novel class of Bicycle Toxin Conjugates appears to be the next game changers in oncology.  

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to the:

• Urothelial Carcinoma Market Insight, Epidemiology and Market Forecast - 2034 report.
• Low-Grade Upper Tract Urothelial Cancer (LG UTUC) - Market Insight, Epidemiology And Market Forecast - 2032
• Non-Muscle Invasive Bladder Cancer (NMIBC) Market Insight, Epidemiology And Market Forecast - 2034