The first patient has been dosed in a phase 2 clinical trial of the treatment combination of samuraciclib and Orserdu (elacestrant) for patients with CDK4/6i resistant hormone receptor (HR)-positive, HER2-negative metastatic breast cancer, according to an announcement from Carrik Therapeutics Ltd., the manufacturer company of samuraciclib.
The trial is aiming to confirm the safest dose of samuraciclib plus Orserdu for patients with metastatic or locally advanced HR-positive, HER2-negative breast cancer. The trial is also evaluating the potential longer-term progression-free survival benefits.
Progression-free survival (PFS) is defined as the length of time between treatment and after treatment when a patient lives with the disease, but it does not worsen, according to National Cancer Institute.
The trial has an estimated 48 participants, according to clinicaltrials.gov, and is expected to be completed in 2025.
Samuraciclib, according to the news release, is a CDK7 inhibitor. CDK7 is an enzyme that “regulates the transcription of cancer-causing genes” that could promote the resistance of anti-hormone therapy, according to the news release.
Orsendu is an oral drug that binds onto proteins, called estrogen receptors, that are found on some breast cancer cells and could cause the growth of these cancer cells, as defined by National Cancer Institute. The drug blocks the estrogen receptors, which controls the cancer cells and prevents growth.
“Dosing the first patient in our phase 2 clinical trial evaluating the combination of samuraciclib and (Orserdu) is an important milestone in our goal of improving outcomes for women fighting metastatic breast cancer,” said Tim Pearson, chief executive officer of Carrick Therapeutics, in the news release. “Our prior studies have validated the biology for (Orserdu) with CDK7, and we are eager to evaluate the potential synergistic benefit of this fully oral combination therapy in patients with advanced breast cancer.”
The study also aims to investigate the level of benefit for patients who do not have a detectable ESR1-mutation and patient selection regarding biomarker potential of TP53-mutation status, according to the news release.
In terms of safety for Orserdu, the drug could cause dyslipidemia (imbalance of lipids, such as cholesterol and triglycerides [fats]) and embryo-fetal toxicities in pregnant women.
Serious side effects occurred in 12% of patients who received Orserdu. The most common serious side effects for more than 1% of patients who received Orserdu were musculoskeletal pain (chronic pain in bones, muscles, ligaments, tendons and nerves) (1.7%) and nausea (1.3%).
The most common side effects overall that occurred in more than 10% of patients included (but were not limited to) musculoskeletal pain (41%), nausea (35%), increased cholesterol (30%), increased aspartate transaminase (low levels of white blood cells) (29%), increased triglycerides (27%), fatigue (26%), decreased hemoglobin (protein in red blood cells that promotes delivery of oxygen to tissues) (26%), vomiting (19%), decreased appetite (15%), diarrhea (13%), headache (12%), constipation (12%), abdominal pain (11%) and hot flush (11%).
Orsendu was approved by the Food and Drug Administration in January 2023 for the treatment of ER-positive, HER2-negative, ESR1-mutated advanced metastatic breast cancer who previously had disease progression after at least one line of endocrine therapy in premenopausal women and adult men.
The drug was approved based on the results from the EMERALD trial, which demonstrated a median progression-free survival of 3.8 months for patients with ESR-1 mutations receiving the drug, compared to a median of 1.9 months when patients received fulvestrant or aromatase inhibitors.
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