Full Press Release Details
Bicycle Therapeutics Announces Data Updates
Across Zelenectide Pevedotin Program and Development Strategy Leveraging NECTIN4 Gene Amplification
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
Bicycle Therapeutics to host conference call
and webcast with management and oncology experts on Friday, Dec. 13, at 8 a.m. ET
CAMBRIDGE, England & BOSTON, Dec. 12, 2024 - Bicycle Therapeutics
plc (NASDAQ: BCYC), a pharmaceutical company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic
peptide (Bicycle ) technology, today announced the presentation of 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 (SABCS)
in San Antonio, Texas. The company also announced topline combination data for zelenectide pevedotin plus pembrolizumab in previously
untreated (first-line) cisplatin-ineligible patients with metastatic urothelial cancer (mUC), provided an enrollment and timeline update
for the company's Phase 2/3 Duravelo-2 trial and shared topline monotherapy data for zelenectide pevedotin in non-small cell lung
cancer (NSCLC) patients with NECTIN4 gene amplification. Bicycle Therapeutics will host a conference call and webcast tomorrow,
Dec. 13, at 8 a.m. ET to review the data updates for zelenectide pevedotin and discuss its development strategy leveraging NECTIN4
gene amplification. Management will be joined by oncology experts Sherene Loi, M.D., Ph.D., from the Peter MacCallum Cancer Centre
in Melbourne, Australia, and Niklas Kl mper, M.D., from the University Hospital Bonn in Germany.
"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 leveraging
NECTIN4 gene amplification, position Bicycle as a leader in addressing Nectin-4 associated cancers," said Bicycle Therapeutics
CEO Kevin Lee, Ph.D. "We are encouraged by the topline zelenectide pevedotin data in combination with pembrolizumab in first-line
mUC patients, which demonstrate zelenectide pevedotin's response data are in line with other drug conjugates used to treat mUC while
its safety and tolerability profile continues to be differentiated. Additionally, we are very pleased with our progress in enrolling our
Duravelo-2 registrational trial for zelenectide pevedotin in mUC and look forward to providing dose selection and topline data in the
second half of next year."
Dr. Lee continued: "While early, the zelenectide pevedotin monotherapy
data in breast cancer and NSCLC patients with NECTIN4 gene amplification underscore its promising anti-tumor activity and solidify
our next steps for the therapy's development. By leveraging NECTIN4 gene amplification, we expect to be able to identify
the patients who may most benefit from zelenectide pevedotin and accelerate development for solid tumor indications beyond bladder cancer.
Over the course of 2025, we plan to initiate Phase 1/2 trials evaluating zelenectide pevedotin in NECTIN4 gene-amplified breast
cancer, lung cancer and multiple other cancers."
Topline Zelenectide Pevedotin Plus Pembrolizumab Combination Data
in First-line mUC Highlights
Zelenectide 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/m2 weekly plus pembrolizumab 200 mg once every three weeks in 22 first-line cisplatin-ineligible patients with
| 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
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). In each cohort, two doses of zelenectide pevedotin -
5 mg/m2 weekly and 6 mg/m2 two weeks on, one week off - are being initially assessed. Based on enrollment
progress, the company plans to report dose selection and topline data for both cohorts in the second half of 2025.
Zelenectide Pevedotin Monotherapy Data in Breast Cancer Patients
with NECTIN4 Gene Amplification Highlights (Presented at 2024 SABCS)
Gene amplification is a common mechanism by which cancer cells gain
function. Bicycle Therapeutics identified that the NECTIN4 gene sits on a commonly amplified chromosomal site in cancer, creating
more copies of the gene and often translating to more protein expression. Since zelenectide pevedotin binds to Nectin-4, it was hypothesized
that NECTIN4 gene amplification may predict response and could serve as a biomarker for therapy stratification.
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/m2 weekly.
Of the 38 breast cancer patients enrolled, 35 patients were efficacy
evaluable. Additionally, 23 breast cancer patient samples were available for NECTIN4 testing, of which 8 demonstrated NECTIN4 gene
amplification or harbored NECTIN4 polysomy. 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. |
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 with NECTIN4 gene amplification,
particularly among those with TNBC who urgently need new treatment options," said Professor Sherene Loi, M.D., Ph.D., consultant
medical oncologist in the Breast Unit and group leader at the Peter MacCallum Cancer Centre in Melbourne, Australia. "As innovative
and genomically targeted therapies for breast cancer continue to emerge, these findings position zelenectide pevedotin as a promising
potential new therapy and NECTIN4 gene amplification as a novel target for breast cancer drug development."
The poster presentation, "Enhanced anti-tumor activity of zelenectide
pevedotin in triple-negative breast cancer (TNBC) patients with NECTIN4 gene amplification" is available in the Publications
section of the Bicycle Therapeutics website.
Topline Zelenectide Pevedotin Monotherapy Data in NSCLC Patients
with NECTIN4 Gene Amplification Highlights
The 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/m2 weekly.
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. Five out of 6
patients with NECTIN4 gene amplification were efficacy evaluable. 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. |
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
Overview of Development Strategy Leveraging NECTIN4 Gene
Bicycle Therapeutics plans to advance development of zelenectide pevedotin
in broader indications outside of mUC utilizing a NECTIN4 gene amplification strategy to target patients who have the potential
for significantly deeper responses.
Over the course of 2025, Bicycle Therapeutics plans to initiate several
additional Phase 1/2 trials to assess zelenectide pevedotin in NECTIN4 gene-amplified breast cancer, lung cancer and multiple other
cancers. Through this strategy, the company believes it has the opportunity to become the leader in addressing Nectin-4 associated cancers
and potentially transform the treatment landscape for thousands of patients in the United States.
Conference Call Details