Arvinas And Pfizer Present Phase 1b Data For Breast Cancer Combo Therapy

Arvinas, Inc. and Pfizer Inc., have shared preliminary data from the ongoing Phase 1b segment of the TACTIVE-U sub-study. The trial is examining vepdegestrant in combination with abemaciclib in patients with locally advanced or metastatic estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. These results will be presented as a poster at the 2024 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas.

In this preliminary analysis of 16 patients, the combination of abemaciclib (150 mg twice daily) and the recommended Phase 3 dose of vepdegestrant (200 mg once daily) showed a tolerable safety profile. The clinical benefit rate was encouraging, reaching 62.5% in patients with both mutant ESR1 and wild-type ESR1 disease, all of whom had previously been treated with a CDK4/6 inhibitor.

Noah Berkowitz, M.D., Ph.D., Chief Medical Officer at Arvinas, said in a statement, “The preliminary results from this Phase 1b sub-study in patients whose cancer had previously progressed after receiving a CDK4/6 inhibitor are encouraging. 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.”

Pharmacokinetic data revealed no significant drug-drug interaction between vepdegestrant and abemaciclib, with no meaningful effect on the exposure to abemaciclib. The safety profile observed was in line with what is known for abemaciclib and consistent with data from previous vepdegestrant trials. These results support the ongoing Phase 2 portion of the study, which is evaluating the combination of full-dose abemaciclib (150 mg BID) and vepdegestrant (200 mg QD) in advanced breast cancer patients who have previously been treated with CDK4/6 inhibitors.

“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. 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,” said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. 

The presentation details are 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

Time – 5:30 - 7:00 p.m. CDT