Following a phase 2 analysis of OP-1250 with palbociclib, researchers recommend an OP-1250 dose level of 120 mg/day for future trials.
Join Sean Bohen, MD, PhD, CEO, Olema Oncology, as he discusses the safety outcome of a study on OP-1250, an oral complete estrogen receptor antagonist (CERAN)/selective estrogen receptor degrader (SERD), as a combination therapy with the cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib for patients with advances and/or metastatic receptor (ER)-positive, HER2-negative breast cancer. Findings will be presented in a poster at the San Antonio Breast Cancer Symposium 2022.
PT Staff: The What was the goal of this trial investigating OP-1250 in combination with palbociclib in patients with advanced and/or metastatic estrogen receptor-positive, HER2-negative breast cancer?
Sean Bohen, MD, PhD: The objective of the phase 1a trial of OP-1250 with palbociclib in (ER)-positive tive HER2 negative breast cancer was to establish the combination ability of OP-1250 and palbociclib, which is a CDK4/6 inhibitor. This is really a safety trial at this point. And, we show the pharmacokinetics of the combination that there is no drug-drug interaction between the 2 agents.
PT Staff: What were the endpoints of this trial, and how were the outcomes measured?
Sean Bohen, MD, PhD: The primary endpoint of the trial is safety. So what you measure with increasing doses of OP-1250 with palbociclib is adverse events and tolerability.
What we found as we dose escalated OP-1250, which is a complete estrogen receptor antagonist, and a potent selective estrogen receptor degrader, was that the overall tolerability of the combination even at our highest dose level 120 mg/day of OP-1250 was comparable to what has been established as the tolerability profile of palbociclib plus an AI or fulvestrant, which is the current standard of care palbociclib endocrine agent combination.
We did not see any enhanced toxicity with OP-1250 and palbociclib. The primary adverse event that occurs with palbociclib is neutropenia, and that neutropenia was seen in this trial— but there were no dose limiting toxicities, the neutropenia was manageable and reversible with dose reduction (or was manageable and reversible with doses being held or dose reduction) as is typically the case when palbociclib is combined with an AI or fulvestrant.
The other endpoint that was measured in the trial was to look at the pharmacokinetics of both palbociclib and OP-1250 in the context of the combination. This is important because some other agents in the third class have been found to have a drug-drug interaction where they induce the metabolism of the palbociclib. In our case, in this trial, we did not see a difference in the exposure of OP-1250 or palbociclib as a combination versus what would be expected if they were given as a single agent.
PT Staff: Were there any other results worth noting regarding dose escalation and dose expansion for this combination of OP-1250 and palbociclib? What the future may hold?
Sean Bohen, MD, PhD: It's too early to look at response in this population at this point in time. Well, what will happen next is that we will expand at 120 mg of OP-1250 with palbociclib. The important point of this trial is that we are able to give our recommended single agent phase 2 dose of OP-1250. Again 120 mg orally per day with palbociclib—and that gives us the basis to be able to further explore the tolerability and anti-tumor activity of this combination with the goal of establishing safety and tolerability to be able to begin a first line ER positive her two negative breast cancer pivotal trial.Single Agent Phase 2 Dose Recommended for Novel HER2 Breast Cancer Therapeutic, OP-1250.