Phase 2/3 study launching of targeted therapy BT8009 in urothelial carcinoma

The phase 2/3 Duravelo-2 trial exploring BT8009 in patients with metastatic urothelial carcinoma is scheduled to launch in the first quarter of 2024, according to Bicycle Therapeutics, the developer of the novel targeted therapy.¹

The Duravelo-2 trial is exploring BT8009 in both treatment-naïve and previously treated patients with urothelial carcinoma.

The investigational agent BT8009 targets the tumor antigen Nectin-4, which has elevated expression levels in urothelial cancer.1 The FDA previously granted BT8009 a Fast Track Designation for the treatment of adult patients with previously treated, locally advanced or metastatic urothelial cancer.² The designation is intended to expedite the review and development of BT8009 in this setting.

"We prepared a robust and innovative clinical development plan for BT8009, with the goal of getting this much-needed therapy to patients as quickly as possible. We are pleased to have reached alignment with the FDA on the registrational trial design, dose selection and clinical trial endpoints that could support potential accelerated approval in a broad metastatic bladder cancer population," Santiago Arroyo, MD, PhD, chief development officer at Bicycle Therapeutics, stated in a press release.¹ "In preparation for this positive outcome, we have put in place the clinical infrastructure that will allow us to start the registrational trial early next year."

The Duravelo-2 trial will have 2 cohorts. Cohort 1 will include patients with metastatic urothelial carcinoma who have not had prior therapy. These patients will receive 1 of 2 dose levels of BT8009 along with standard pembrolizumab (Keytruda). Once the optimal dose of BT8009 has been determined, the BT8009/pembrolizumab combination will be compared with chemotherapy to determine which approach delivers a superior objective response rate (ORR) and progression-free survival in this setting.¹

Cohort 2 of Duravelo-2 will enroll patients with previously treated metastatic urothelial carcinoma who will initially receive 1 of 2 dose levels of single-agent BT8009 to determine the optimal dose. Once this dose is established, an additional arm will be added consisting of BT8009 plus standard pembrolizumab. The efficacy of BT8009/pembrolizumab in this setting will be determined by comparing ORR in the Cohort 2 patients with “historical control data,” according to Bicycle.¹

Previously results for BT8009

Interim phase 1 results from a phase 1/2 trial (NCT04561362) investigating BT8009 in patients with advanced urothelial cancer and other solid tumors were shared in an oral presentation at the 2022 AACR 2022 Annual Meeting.³

Findings indicated that among 4 response evaluable patients with urothelial carcinoma in the 2.5 mg/m² cohort, BT8009 yielded 1 confirmed partial response (PR) and stable disease in 2 other patients. Overall, investigators reported an ORR of 25% and disease control rate (DCR) of 75% in this cohort.³

Among 8 response evaluable patients who received 5.0 mg/m2 of BT8009 weekly, 4 had a confirmed complete response (CR) or PR, which included 1 patient with a CR, 3 patients with a PR, and 2 patients with stable disease. Investigators reported an ORR of 50% and a DCR of 75% for the cohort.³

As of the data cutoff date of March 7, 2022, the median duration of response (DOR) had not been reached in either cohort. All patients in the 5.0 mg/m2 cohort had received at least 2 previous lines of therapy and median of 3 lines.³

“At Bicycle Therapeutics, we are committed to using our novel platform to develop precision targeted therapeutics and improve the lives of patients who are battling devastating diseases. This is why, in line with the philosophy of the FDA’s Project FrontRunner and following the agency’s recent draft guidance on accelerated approval of oncology therapeutics, we have initially focused on defining the regulatory path for BT8009 in untreated patients. We believe today’s announcement is good news for patients, and we are greatly appreciative of the FDA for their collaboration and guidance," Kevin Lee, PhD, CEO of Bicycle Therapeutics, stated in a press release.¹ "As we look to the rest of 2023, we continue to make progress in our research and development programs and look forward to providing updates on BT8009, BT5528 and BT7480 later this year."

References

1. Bicycle Therapeutics Announces Expedited Development Plan for BT8009 in Metastatic Bladder Cancer. Published online and accessed September 11, 2023. https://investors.bicycletherapeutics.com/news-releases/news-release-details/bicycle-therapeutics-announces-expedited-development-plan-bt8009

2. Bicycle Therapeutics announces FDA fast track designation granted to BT8009 for the treatment of adult patients with previously treated locally advanced or metastatic urothelial cancer. News release. Bicycle Therapeutics. January 4, 2023. Accessed January 5, 2023. bit.ly/3VLNl3K

3. Bicycle Therapeutics announces interim BT8009 phase I clinical trial results at the 2022 AACR Annual Meeting. News release. Bicycle Therapeutics. April 11, 2022. Accessed January 5, 2023. bit.ly/3jHmBDZ