Bicycle Therapeutics Lead Cancer Drug Combined With Merck's Blockbuster Drug Shows 60% Overall Response Rate In Urothelial Cancer Patients

On Thursday, Bicycle Therapeutics plc BCYC announced that it presented data showing the enhanced anti-tumor activity of zelenectide pevedotin monotherapy in breast cancer patients with NECTIN4 gene amplification at the 2024 San Antonio Breast Conference Symposium.

The company revealed topline combination data for zelenectide pevedotin plus Merck & Co Inc’s MRK Keytruda (pembrolizumab) in previously untreated (first-line) cisplatin-ineligible patients with metastatic urothelial cancer (mUC).

Topline results from the ongoing Phase 1/2 Duravelo-1 trial evaluating zelenectide pevedotin weekly plus pembrolizumab once every three weeks showed:

• 60% overall response rate (ORR) (12/20) among efficacy-evaluable patients. Of the responses, five were confirmed, and seven were unconfirmed at the time of the data cut. Fifteen patients remained on treatment at the time of the data cut.
• The safety and tolerability profile was broadly consistent with late-line Duravelo-1 monotherapy and combination cohorts.
• Adverse events of clinical interest, such as peripheral neuropathy, skin reactions, and eye disorders, were primarily low-grade.
• There was one report of Grade 3 sensory peripheral neuropathy and one report of Grade 3 rash, both of which were transient and reverted to Grade 1 upon dose interruption.

Bicycle Therapeutics is currently conducting the Phase 2/3 Duravelo-2 trial evaluating zelenectide pevedotin plus pembrolizumab versus chemotherapy in first-line mUC (Cohort 1), and zelenectide pevedotin monotherapy and in combination with pembrolizumab in late-line mUC (Cohort 2).

Based on enrollment progress, the company plans to report dose selection and topline data for both cohorts in the second half of 2025.

The company also conducted a post-hoc analysis of 38 heavily pretreated breast cancer patients enrolled in Duravelo-1, of which 32 were confirmed to have triple-negative breast cancer (TNBC).

Of the 38 breast cancer patients enrolled, 35 patients were efficacy evaluable. Results showed:

• 62.5% ORR (5/8) among breast cancer patients with NECTIN4 gene amplification or polysomy, compared to 14.3% ORR (5/35) among all efficacy-evaluable breast cancer patients.
• Of the 5 partial responses, 4 were confirmed and 1 was unconfirmed.
• No responses in non-amplified or non-polysomy patients.

Of the 32 TNBC patients enrolled, 30 patients were efficacy evaluable. Additionally, 19 TNBC patient samples were available for NECTIN4 testing, of which 7 demonstrated NECTIN4 gene amplification or harbored a NECTIN4 polysomy. Results showed:

• 57.1% ORR (4/7) among TNBC patients with NECTIN4 gene amplification or polysomy, compared to 13.3% ORR (4/30) among all efficacy-evaluable TNBC patients.
• Of the 4 partial responses, 3 were confirmed and 1 was unconfirmed.
• All 3 TNBC patients with NECTIN4 gene amplification who responded to zelenectide pevedotin had prior treatment with sacituzumab govitecan.
• No responses in non-amplified or non-polysomy patients.

The company conducted a post-hoc analysis of 40 pretreated patients with NSCLC with NECTIN4 Gene Amplification enrolled in Duravelo-1.

Of the 40 patients enrolled, 34 patients were efficacy evaluable. Additionally, 19 patient samples were available for NECTIN4 testing, of which 6 demonstrated NECTIN4 gene amplification. Results showed:

• 40.0% ORR (2/5) among patients with NECTIN4 gene amplification, compared to 8.8% ORR (3/34) among all efficacy-evaluable patients.
• Of the 3 partial responses, 2 were confirmed and 1 was unconfirmed.
• Out of 19 patients tested for NECTIN4 gene amplification, none of the non-amplified patients responded.

Price Action: BCYC stock is up 1.19% to $20.35 premarket at the last check on Friday.

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