New Drug Could Change Treatment Landscape for ER-Positive, HER2-Negative Breast Cancer

Video

Researchers discovered the most common single gene mutation that causes treatment-resistance in first- line ER-positive or HER2-negative breast cancer treatment with a CDK4/6 inhibitor.

Join Pharmacy Times as we talk with Sean Bohen, MD, PhD, CEO of Olema Oncology, about the possibilities of a new treatment that acts as both a complete estrogen receptor antagonist and a selective estrogen receptor degrader for patients with ER-positive HER2-neagtive breast cancer. Bohen presented these findings at the San Antonio Breast Cancer Symposium on December 7.

PT Staff: What is your perspective on the landscape of breast cancer drug development for the selective estrogen receptor degrader (SERD) class, and what may the future hold?

Sean Bohen, MD, PhD: The certain class has already established clinical activity in the second- and third line setting of ER-positive HER2-negative breast cancer. That was established with elacestrant, 1 molecule that had a positive phase 3 trial called EMERALD. The opportunity here is to do even better. We know that elacestrant, while a selective estrogen receptor degrader (SERD), is not a complete estrogen receptor antagonist.

OP-1250 is both a complete estrogen receptor antagonist (CERAN) and a SERD. The opportunity here is to improve upon the elacestrant (EMERALD) result in the second- or third-line setting. And we will begin that first phase 3 trial in the middle of next year. The next opportunity—and perhaps the most exciting— is that (we have learned) over the past year, the most common single gene mutation that occurs with resistance to the treatment of first line ER-positive or HER2-negative breast cancer with a CDK4/6 inhibitor and an aromatase inhibitor (AI), or fulvestrant, an estrogen receptor 1 (ESR1) activating mutation. This results in activation of the estrogen receptor in the absence of the hormone estrogen. This means that most commonly— in about 50% of cases—tumors are growing with a CDK4/6 inhibitor plus an AI (or fulvestrant) by turning on the estrogen receptor.

We have demonstrated that OP-1250 has clinical activity against these ESR1 mutant receptor tumors. And that gives the opportunity, in combination in a first-line setting, to suppress the most common resistance mutation, and thereby extend the progression free survival (PFS) benefit that is inferred by a CDK4/6 inhibitor plus an endocrine agent in the first-line setting.

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