First Patients Dosed in Phase 1 Trial Testing ARV-471 in Advanced, ER-Positive Breast Cancer

The first patients have been dosed in a Phase 1 trial evaluating Arvinas‘ experimental therapy ARV-471 for locally-advanced or metastatic ER-positive, HER2-negative breast cancer.

Approximately 80% of newly-diagnosed breast cancers produce a protein called an estrogen receptor (ER). In these cancers, the hormone estrogen binds to its receptor, causing the cells to grow and multiply. Therefore, anti-estrogen therapies — such as tamoxifen and fulvestrant (brand name Faslodex by AstraZeneca) — that reduce estrogen production or block the ER are standard-of-care for this type of cancer.

However, many patients become resistant to these therapies, which results in advanced cancers that are more difficult to treat, so new therapeutic options are needed.

Arvinas is a biopharmaceutical company developing therapies that degrade disease-causing proteins. It developed a platform called PROTAC, which can target any protein for degradation by the body’s natural mechanisms.

ARV-471 is an oral investigational therapy that uses PROTAC technology to target the ER for degradation.

“ARV-471 is a potent ER degrader that has demonstrated significant anti-tumor activity in preclinical models, and we are hopeful it will address an important need for patients with advanced ER-positive breast cancer not adequately treated with current standards of care,” Ronald Peck MD, chief medical officer of Arvinas, said in a news release.

The ongoing Phase 1 trial (NCT04072952) will evaluate the effects of ARV-471 for the first time in humans. The study, which is still recruiting participants, plans to enroll 36 people with locally-advanced or metastatic ER-positive, HER2-negative breast cancer.

To be eligible, patients must have received at least two prior hormone therapies — given for either local or advanced disease — a CDK4/6 inhibitor such as Verzenio (abemaciclib) or Ibrance (palbociclib), and up to three prior chemotherapies in the locally advanced or metastatic setting.

Primary endpoints include safety, tolerability, and pharmacokinetics — how the substance is absorbed, processed, and degraded by the body — of the investigational therapy.

Secondary endpoints include pharmacodynamics — the effects of the substance in the body — and anti-tumor activity.

In preclinical models, ARV-471 degraded nearly all ER proteins from cancer cells, which resulted in a superior anti-tumor activity than that of standard-of-care therapies. ARV-471 showed similar results when tested alone or in combination with CDK 4/6 inhibitors, such as Ibrance.

In future trials, Arvinas plans to investigate the efficacy of ARV-471 as a monotherapy and in combination with other treatments, such as CDK 4/6 inhibitors.

“ARV-471 is Arvinas’ second targeted protein degrader to enter the clinic, making this another exciting and significant development for our company and the field,” Peck said.

Arvinas anticipates preliminary data to be released from the Phase 1 trial in 2020.

ARV-110, the company’s first protein degrader that targets the androgen receptor, recently received fast-track designation by the U.S. Food and Drug Administration. An ongoing Phase 1 trial (NCT03888612) is testing the therapy in men with metastatic castration-resistant prostate cancer.