Company: ARVN
Filing Date: 2025-02-11
Form Type: 10-K
Source: 0001655759-25-000016
Chunk: 123

Company: ARVINAS, INC.
Filing Date: 2025-02-11
Form: 10-K
Item: Item 1
Chunk 123
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 potential interaction with ROS, concomitant use of ROS was precluded. 

In 2020, we amended the protocol for our Phase 1 clinical trial for bavdegalutamide to include the addition of a Phase 2 expansion cohort. Based on our observations of a molecularly defined, late-line population with a particularly strong response to bavdegalutamide in the Phase 1 portion of the trial, we designed our Phase 2 dose expansion to assess bavdegalutamide in four specific subgroups: patients with tumors with AR T878X (T878X = T878A or T878S) and/or H875Y mutations but excluding other AR variants; patients with tumors with wild-type AR or AR alterations other than T878X, H875Y, L702H, and AR-V7; patients with tumors with AR-V7 or L702H, which are variants of AR that, preclinically, bavdegalutamide did not degrade, or did not degrade potently, respectively; and patients with biomarker agnostic tumors treated with no more than one prior NHA, such as enzalutamide or abiraterone, and had no prior chemotherapy. 

In the fourth quarter of 2020, we initiated the ARDENT Phase 2 expansion portion of the trial at a dose of 420 mg once-daily, the recommended Phase 2 dose, or RP2D. 

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In February 2022, we announced completed Phase 1 and interim ARDENT data for bavdegalutamide with a data cut-off date of December 20, 2021 at the 2022 American Society of Clinical Oncology Genitourinary Cancers Symposium. We reported that bavdegalutamide showed reduced PSA50 in 46% of the 28 patients with tumors harboring AR T878X/H875Y mutations. These results also demonstrated PSA declines and tumor regressions in patients without tumors harboring AR T878X/H875Y mutations, suggesting an opportunity to develop bavdegalutamide more broadly in prostate cancer.

As of the data cut-off date, 195 patients were enrolled across the Phase 1/2 clinical trial (71 in Phase 1; 124 in Phase 2). The Phase 1 dose escalation trial evaluated bavdegalutamide at doses ranging from 35–700 mg, once-daily, or 210–420 mg twice-daily, in patients with m