Bicycle Therapeutics Announces Data Updates Across Zelenectide Pevedotin Program and Development Strategy Leveraging NECTIN4 Gene Amplification
BCYC 12.12.2024
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Recent News
- 01.15.2025 - 43rd Annual J.P. Morgan Healthcare Conference
- 01.13.2025 - Bicycle Therapeutics Announces Updated Topline Zelenectide Pevedotin Data and Highlights 2025 Strategic Priorities and Milestones
- 01.09.2025 - Bicycle Therapeutics to Present at 43rd Annual J.P. Morgan Healthcare Conference
Recent Filings
Topline combination data for zelenectide pevedotin plus pembrolizumab in first-line metastatic urothelial cancer demonstrated a 60% overall response rate, in line with existing therapies
Dose selection and topline data from Phase 2/3 Duravelo-2 trial planned for 2H 2025
Heavily pretreated breast cancer and non-small cell lung cancer patients with NECTIN4 gene amplification and/or polysomy demonstrated an enhanced response to zelenectide pevedotin
Company to advance development strategy leveraging NECTIN4 gene amplification, with Phase 1/2 trials in breast cancer, lung cancer and multi-tumor planned for 2025
“The totality of the data shared today builds on the breadth of previously reported data for zelenectide pevedotin that we believe, when combined with our ambitious development strategy leveragingNECTIN4gene amplification, position Bicycle as a leader in addressing Nectin-4 associated cancers,” said
Topline Zelenectide Pevedotin Plus Pembrolizumab Combination Data in First-line mUC HighlightsZelenectide pevedotin is a Bicycle®Toxin Conjugate (BTC®) targeting Nectin-4, a well-validated tumor antigen. Topline results from the ongoing Phase 1/2 Duravelo-1 trial evaluating zelenectide pevedotin 5 mg/m2weekly plus pembrolizumab 200 mg once every three weeks in 22 first-line cisplatin-ineligible patients with mUC showed:
- 60% overall response rate (ORR) (12/20) among efficacy-evaluable patients. Of the responses, 5 were confirmed and 7 were unconfirmed at the time of the data cut. Fifteen patients remained on treatment at the time of the data cut.
- 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.
More detailed data from this study will be presented at a future medical meeting.
Zelenectide Pevedotin Monotherapy Data in Breast Cancer Patients withNECTIN4Gene Amplification Highlights (Presented at 2024 SABCS)Gene amplification is a common mechanism by which cancer cells gain function.
The company 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). The majority of patients were treated with zelenectide pevedotin 5 mg/m2weekly.
Of the 38 breast cancer patients enrolled, 35 patients were efficacy evaluable. Additionally, 23 breast cancer patient samples were available forNECTIN4testing, of which 8 demonstrated NECTIN4 gene amplification or harboredNECTIN4polysomy. Results showed:
- 62.5% ORR (5/8) among breast cancer patients withNECTIN4gene 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 forNECTIN4testing, of which 7 demonstratedNECTIN4gene amplification or harbored aNECTIN4polysomy. Results showed:
- 57.1% ORR (4/7) among TNBC patients withNECTIN4gene 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 withNECTIN4gene amplification who responded to zelenectide pevedotin had prior treatment with sacituzumab govitecan.
- No responses in non-amplified or non-polysomy patients.
In this study of heavily pretreated breast cancer patients, zelenectide pevedotin was generally well tolerated, and its safety and tolerability profile was consistent with data from other Duravelo-1 cohorts. Low rates of Grade ≥3 treatment-related adverse events (TRAEs) (34.2%) and Grade ≥3 treatment-related serious adverse events (TRSAEs) (10.5%) occurred. The most common TRAEs were fever (pyrexia), nausea and diarrhea. TRAEs of clinical interest, including peripheral neuropathy (any kind) and skin reactions, were low grade.
“Although the sample size was limited, this post-hoc analysis highlights the encouraging anti-tumor activity of zelenectide pevedotin in breast cancer patients withNECTIN4gene amplification, particularly among those with TNBC who urgently need new treatment options,” said Professor
The poster presentation, “Enhanced anti-tumor activity of zelenectide pevedotin in triple-negative breast cancer (TNBC) patients withNECTIN4gene amplification” is available in the Publications section of the
Topline Zelenectide Pevedotin Monotherapy Data in NSCLC Patients withNECTIN4Gene Amplification HighlightsThe company conducted a post-hoc analysis of 40 pretreated patients with NSCLC enrolled in Duravelo-1. The majority of patients received zelenectide pevedotin 5 mg/m2weekly.
Of the 40 patients enrolled, 34 patients were efficacy evaluable. Additionally, 19 patient samples were available forNECTIN4testing, of which 6 demonstratedNECTIN4gene amplification. Five out of 6 patients withNECTIN4gene amplification were efficacy evaluable. Results showed:
- 40.0% ORR (2/5) among patients withNECTIN4gene 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 forNECTIN4gene amplification, none of the non-amplified patients responded.
The safety and tolerability profile of zelenectide pevedotin was broadly consistent with data from other Duravelo-1 monotherapy cohorts.
More detailed data from this study will be presented at a future medical meeting.
Overview of Development Strategy LeveragingNECTIN4Gene Amplification
Over the course of 2025,
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About
Forward Looking StatementsThis press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding Bicycle’s development of zelenectide pevedotin, BT5528 and BT7480 as well as potential radiopharmaceutical product candidates; the company’s plans to utilize a NECTIN4 gene amplification strategy in the clinical development of zelenectide pevedotin; expectations with respect to Bicycle’s ability to identify the patients who may most benefit from zelenectide pevedotin, to advance or accelerate development of this product candidate for broader indications, including solid tumor cancers beyond bladder cancer, and to become a leader in addressing Nectin-4 associated cancers; the planned initiation of clinical trials of zelenectide pevedotin in breast cancer, lung cancer, and other cancers; the timing and manner of announcement of data and program updates from clinical trials for zelenectide pevedotin, including reporting of dose selection and topline data from the Duravelo-2 trial; and the use of Bicycle’s technology through various partnerships to develop potential therapies in diseases beyond oncology. Bicycle may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including: uncertainties inherent in research and development and in the initiation, progress and completion of clinical trials and clinical development of Bicycle’s product candidates; the risk that Bicycle may not realize the intended benefits of its technology, partnerships or NECTIN4 gene amplification strategy; timing of results from clinical trials; whether the outcomes of preclinical studies and prior clinical trials will be predictive of future clinical trial results; the risk that trials may have unsatisfactory outcomes; potential adverse effects arising from the testing or use of Bicycle’s product candidates; and other important factors, any of which could cause Bicycle’s actual results to differ from those contained in the forward-looking statements, are described in greater detail in the section entitled “Risk Factors” in Bicycle’s Quarterly Report on Form 10-Q filed with the
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