Arvinas/Pfizer reveal Phase 1b data at SABCS 2024

These data were presented in a poster at the 2024 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas  as follows. Title: Vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) Estrogen Receptor (ER) Degrader, Plus Abemaciclib in ER-Positive/Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Advanced or Metastatic Breast Cancer: TACTIVE-U Preliminary Phase 1b Results •  Date: Thursday, December 12, 2024.  

Key findings included in the poster (data cut-off: August 30, 2024):   • 100% of patients had prior treatment with a CDK4/6 inhibitor. • Tolerability is generally consistent with the profile of abemaciclib and with results previously observed in other clinical trials of vepdegestrant. The most common any grade treatment-emergent adverse events (TEAE) were diarrhea, nausea and fatigue.  There were no dose-limiting toxicities and no grade 4 or 5 TEAEs.  • There was no significant drug-drug interaction  and data reflected vepdegestrant has no clinically meaningful effect on abemaciclib exposure.  • Encouraging preliminary antitumor activity is observed with a clinical benefit rate (CBR, defined as the rate of confirmed complete response, partial response, or stable disease ≥ 24 weeks) of 62.5% in all CBR-eligible patients (10/16), 62.5% in patients with mutant ESR1 (5/8), and 62.5% in patients with wild-type ESR1 (5/8).   • The objective response rate (ORR) in evaluable patients was 26.7% overall (4/15), 37.5% in patients with mutant ESR1 (3/8), and 14% in patients with wild-type ESR1 (1/7).   •  Five patients remained on study treatment as of the August 30, 2024 data cut-off.

Arvinas and Pfizer are continuing to evaluate data from the ongoing TACTIVE-U clinical trial program , which includes combinations of vepdegestrant plus abemaciclib, ribociclib or samuraciclib (NCT05548127, NCT05573555, and NCT06125522). These findings support the ongoing Phase II portion of the study, which is evaluating full dose abemaciclib (150mg BID) in combination with vepdegestrant (200 mg QD) in post-CDK4/6 advanced breast cancer.

“The preliminary results from this Phase 1b sub-study in patients whose cancer had previously progressed after receiving a CDK4/6 inhibitor are encouraging,” said Dr. Noah Berkowitz, Chief Medical Officer at Arvinas. “These data further reinforce our belief that vepdegestrant can be used in multiple combination regimens across the metastatic breast cancer setting and has the potential to become a best-in-class backbone ER therapy.

"With vepdegestrant, we aim to develop a novel agent that has the potential to become a new backbone endocrine therapy in ER+ metastatic breast cancer,” said Dr. Roger Dansey,  Chief Development Officer, Oncology, Pfizer.“