FDA Grants FTD to Vepdegestrant in ER+/HER2– Metastatic Breast Cancer

Investigators are currently assessing second-line vepdegestrant monotherapy as part of the ongoing phase 3 VERITAC-2 trial (NCT056546230). Additionally, the novel agent is under evaluation in combination with palbociclib (Ibrance) as frontline therapy in the phase 3 VERITAC-3 trial (NCT05909397).

The FDA has granted fast track designation to vepdegestrant (ARV-471) monotherapy as a treatment for adult patients with estrogen receptor (ER)–positive, HER2-negative locally advanced or metastatic breast cancer who have received prior treatment with endocrine-based therapy, according to a press release from Arvinas and Pfizer.

According to the press release, findings from preclinical studies highlighted ER degradation rates of up to 97% in tumor cells using vepdegestrant. Additionally, the agent yielded tumor shrinkage among ER-driven xenograft models and demonstrated improvements in anti-tumor activity compared with fulvestrant (Faslodex) when administered as monotherapy or with a CDK4/6 inhibitor.

“We are focused on the persisting unmet needs of people with ER-positive, HER2-negative breast cancer and doing all that we can to expedite the development of vepdegestrant as a novel, oral ER-targeted potential therapy for this patient community,” John Houston, PhD, chairperson, chief executive officer, and president at Arvinas, said in the press release. “We are pleased the FDA has granted fast track designation for vepdegestrant, and we continue to believe this investigational drug has the potential to harness the body’s natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins.”

Investigators are currently assessing second-line vepdegestrant monotherapy as part of the ongoing phase 3 VERITAC-2 trial (NCT056546230). Additionally, the novel agent is under evaluation in combination with palbociclib (Ibrance) as frontline therapy in the phase 3 VERITAC-3 trial (NCT05909397).

VERITAC-2 Trial

In the open-label, multi-center VERITAC-2 trial, an estimated enrollment of 560 patients will be randomly assigned to receive vepdegestrant orally once a day as part of a continuous 28-day schedule or fulvestrant intramuscularly on days 1 and 15 of cycle 1 followed by day 1 of each subsequent cycle.

The trial’s primary end point is progression-free survival (PFS) as determined via blinded independent central review (BICR) using RECIST v1.1 criteria. Secondary end points include overall survival (OS), objective response rate (ORR), duration of response (DOR), clinical benefit rate (CBR), safety, and disease-related quality of life.

Patients 18 years and older with loco-regional recurrent or metastatic breast cancer not amenable to surgery or radiotherapy that is ER positive and HER2 negative are able to enroll on the trial. Additional eligibility criteria include having 1 prior line of CDK4/6 inhibitor therapy plus endocrine therapy, radiological progression on or following the last prior line of treatment, measurable disease based on RECIST v1.1 guidelines, and an ECOG performance status of 0 or 1.

VERITAC-3 Trial

Investigators of the open-label, multi-center VERITAC-3 trial will randomly assign an estimated enrollment of 1180 patients to receive vepdegestrant or letrozole (Femara) orally once a day plus palbociclib orally once a day for 21 days as part of a 28-day cycle.

The trial’s primary end points include the incidence of grade 4 neutropenia during the lead-in portion and PFS during the phase 3 portion. Secondary end points include ORR, DOR, CBR, OS, laboratory abnormalities, and plasma concentration.

Those who are 18 years and older with loco-regional recurrent or metastatic, ER-positive, HER2-negative breast cancer not amenable to curative therapy and no prior lines of systemic treatment are eligible for enrollment on the VERITAC-3 trial. Patients are also eligible to enroll if they have an ECOG performance status of 0 to 2.

“The receipt of fast track designation reinforces the potential of vepdegestrant to provide an important new therapeutic option for people with ER-positive, HER2-negative breast cancer whose disease has progressed. We are proud to continue our legacy of developing innovative treatment options for people [with] metastatic breast cancer and look forward to working with the FDA as we advance our development program for vepdegestrant,” Roger Dansey, MD, chief development officer of Oncology at Pfizer, concluded.

Reference

Arvinas and Pfizer’s vepdegestrant (ARV-471) receives FDA fast track designation for the treatment of patients with ER+/HER2- metastatic breast cancer. News release. Arvinas, Inc. and Pfizer, Inc. February 6, 2024. Accessed February 8, 2024. http://tinyurl.com/4f9c8mfp