Updated Phase 1/2 Data Highlights Vepdegestrant Benefits for ER+ HER2- Breast Cancer


A Phase 1/2 clinical trial sought to evaluate the potential of vepdegestrant as a therapeutic option for heavily pretreated individuals with estrogen receptor-positive (ER+) and HER2 negative (HER2-) advanced breast cancer. To be included in the study, patients must have previously tried at least one CDK4 or CDK6 inhibitor, two endocrine therapies, and up to 3 lines of chemotherapy. Vepdegestrant is an investigational oral PROTAC® estrogen receptor protein degrader that targets the estrogen receptor; estrogen receptor signaling has been shown to drive many breast cancers.

Within this study, researchers explored the safety, tolerability, antitumor activity, and pharmacokinetics. This study also laid out a maximum tolerated dose via its dose-escalation phase, as well as the ideal dose for further studies.

Kristi Rosa of OncLive reports that updated data from the dose-escalation portion of the study was presented during the 2023 European Society for Medical Oncology (ESMO) Congress. The data highlights the favorable tolerability of vepdegestrant and its promise in treating ER+ HER2- breast cancer. Three people received 30mg vepdegestrant daily, three people received 60mg vepdegestrant, thirteen people received 100mg, seven received 120mg, eight received 200mg, 15 received 360mg, 22 received 500mg, and 4 received 700mg.

Findings from the study, with a median follow-up length of 13.8 months for initial data and an additional 20 months for the presented data, show that:

  • Researchers recommended 200mg vepdegestrant for Phase 2 studies.
  • Vepdegestrant was relatively well-tolerated across all given doses. However, a majority of participants (96.4%) experienced some side effects relating to treatment. Most of these were mild or moderate, including fatigue, headaches, nausea, muscle pain, constipation, and hot flashes. A smaller number of patients discontinued treatment due to side effects.
  • The clinical benefit rate across all doses was 36.1%, and 48.8% in people with ESR1 gene mutations. Clinical benefit rate refers to the number of patients who achieved a partial response, complete response, or disease stability for 6+ months.

Moving forward, vepdegestrant is also being evaluated in the Phase 3 VERITAC-2 and VERITAC-3 studies to evaluate 200mg vepdegestrant as compared to fulvestrant, and vepdegestrant in conjunction with palbociclib as compared to Femara and palbociclib, respectively.

About HER2- Breast Cancer

Breast cancer is, as the name suggests, cancer that forms in breast tissue. Although breast cancer can affect both males and females, it is the 2nd most common cancer in females. There are a number of factors you should know about breast cancer that play a role in treatment and prognosis such as the cancer’s stage, subtype, size, location, and proteins.

WebMD explains that human epidermal growth factor 2 (HER2) is a key protein receptor that plays a role in cell growth. If the cancer is HER+, it’s often more aggressive; the cancer makes extra HER2, contributing to tumor growth. Alternately, shares WebMD:

If your doctor says your breast cancer is HER2-negative, it means your cancer isn’t making a lot of extra HER2. Breast cancer that’s HER2-negative tends to have a better outlook than those that are HER2-positive, since HER2-negative makes the cancer less aggressive.

Symptoms related to HER2- breast cancer may include:

  • Unusual fatigue
  • Unintentional weight loss
  • Dimpled skin (or other skin changes) on the breast
  • Breast swelling, thickening, or pain (or other changes in breast size, shape, or appearance)
  • Nipple pain
  • Clear or bloody nipple discharge
  • Inverted nipples
  • Breast skin pitting, peeling, scaling, crusting, redness, or flaking
  • Swollen lymph nodes near the armpits or collarbones

Right now, there are varied options to treat HER2- breast cancer. These include radiation, chemotherapy, endocrine therapies, surgery, or immunotherapy.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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