Arvinas and Pfizer announced preliminary data from the ongoing Phase 1b portion of the TACTIVE-U sub-study of vepdegestrant in combination with abemaciclib among patients with locally advanced or metastatic estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. These data will be presented in a poster at the 2024 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas.
Preliminary results from 16 patients in the Phase 1b sub-study demonstrated a tolerable safety profile for the combination of abemaciclib 150 mg twice daily (BID) with the recommended Phase 3 monotherapy dose of vepdegestrant (200mg once daily; QD). An encouraging clinical benefit rate of 62.5 per cent was observed among patients with both mutant ESR1 and wild-type ESR1 disease who had all been previously treated with a CDK4/6 inhibitor.
Pharmacokinetic data demonstrated no significant drug-drug interaction between vepdegestrant and abemaciclib and no clinically meaningful effect on abemaciclib exposure was observed. In addition to tolerability, the results demonstrated a safety profile consistent with both the known properties of abemaciclib and observed data in other clinical trials for vepdegestrant. These findings support the ongoing Phase 2 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 Noah Berkowitz, M.D., Ph.D., Chief Medical Officer, 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. We are pleased to continue in the Phase 2 portion of the study evaluating the standard starting dose of abemaciclib in combination with vepdegestrant.”
“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 Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. “We are pleased to see these initial results, which complement previously reported data demonstrating the potential of combination therapy with vepdegestrant to address unmet needs for patients.”
Additional details on the TACTIVE-U poster presentation at SABCS are below:
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
Time: 5:30 – 7:00 p.m. CDT
Poster: P4-12-03
Key findings included in the poster (data cut-off: August 30, 2024):
- 100 per cent 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 grade treatment-emergent adverse events (TEAE) were diarrhoea, 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 that 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 per cent in all CBR-eligible patients (10/16), 62.5 per cent in patients with mutant ESR1 (5/8), and 62.5 per cent in patients with wild-type ESR1 (5/8).
- The objective response rate (ORR) in evaluable patients was 26.7 per cent overall (4/15), 37.5 per cent in patients with mutant ESR1 (3/8), and 14 per cent 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, which includes combinations of vepdegestrant plus abemaciclib, ribociclib or samuraciclib (ClinicalTrials.gov Identifiers: NCT05548127, NCT05573555, and NCT06125522).