On February 6, 2024, AVinas and Pfizer developed Vepdegestrant (ARV-471), an oral estrogen receptor PROTAC protein degraderGranted Express Entry status by the US FDAfor estrogen receptor (ER)-positive human growth epidermal growth factor 2 (HER2)-negative (ER+ HER2-) locally advanced or metastatic breast cancer** patients.
VepdeGestrant is a novel oral, ER-targeted protein degrader (PROTAC) jointly developed by Arvinas and PfizerDesigned to specifically target and degrade ER
In preclinical studies, Vepdegestrant showed up to 97% ER degradation in tumor cells, when administered as a single agent in multiple ER-driven xenograft modelsInduces robust tumor shrinkage。and showed enhanced antitumor activity compared to the standard-of-care agent fulvestrant, either as a single agent or in combination with a CDK4 6 inhibitor.
Common Name:vepdegestrant
Codename:arv-471
Manufacturer:Arvinas and Pfizer
Target:er
First approved in the United States:Not yet approved.
Approved for the first time in China:Not yet approved.
Clinical data
In the Phase I II Veritac study, the safety and efficacy of Vepdegestrant (ARV-471) in combination with the CDK4 6 inhibitor iBrance (palbociclib, palbociclib) in severely pretreated patients with locally advanced or metastatic ER+ HER2- breast cancer (n=46) were evaluated. These patients have received at least 1 endocrine-based** regimen and 2 chemotherapy regimens for advanced disease.
Data from the study was shared at the 2023 San Antonio Breast Cancer Symposium with a data cut-off date of June 6, 2023.
The results of the study showed a clinical benefit rate (CBR) of 10 per cent in all evaluable patients (n=46).；In patients (n=21) who received the recommended dose (RP3D) of 200 mg** in the phase III trial, the CBR was
In addition, CBR in patients with ESR1 mutations (n=29) was；At an RP3D of 200 mg, the CBR was（n=11/14）。In the subgroup of patients with ESR1 wild-type disease (n=15), CBR was；In patients given RP3D** (n=7), the CBR was:
Among the 31 evaluable patients with measurable disease at baseline, the objective response rate (ORR) was；Patients who received RP3D** had a higher ORR, for:。In patients with ESR1 mutations and ESR1 wild-type, the ORRs werewith；In patients who received RP3D**, the ORRs were:with
In addition, the median progression-free survival (PFS) of all 46 patients was11.1 month。In the ESR1 mutant and wild-type subgroups, the median PFS was 11., respectively0 months and 111 monthIn patients who had previously received a CDK4 6 inhibitor (n=40), the median PFS was 110 months; In patients (n=6) who had not previously received a CDK4 6 inhibitor, the median PFS was 193 months.
In terms of safety, the Vepdegestrant in combination with ibrance** has a controlled toxicity profile.
Summary
If approved, VepdeGestrant could provide a valuable new ** option for patients with ER+ HER2- breast cancer who have progressed after endocrine**.
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