NEW YORK – Carrick Therapeutics on Wednesday began treating patients with CDK4/6 inhibitor-resistant, hormone receptor (HR)-positive, HER2-negative metastatic breast cancer in a Phase II trial evaluating its CDK7 inhibitor samuraciclib with Menarini Group's oral selective estrogen receptor degrader (SERD) Orserdu (elacestrant).
The US Food and Drug Administration earlier this year approved Orserdu as a second-line treatment for estrogen receptor (ER)-positive HER2-negative advanced breast cancer patients harboring ESR1 mutations.
In the first portion of Carrick's Phase II trial, researchers will evaluate tolerability and pharmacokinetics and determine the recommended dose of samuraciclib and Orserdu. Once the dose is identified, researchers will enroll an additional 30 patients to evaluate progression-free survival and other efficacy endpoints.
Researchers will also perform circulating tumor DNA (ctDNA) analysis to evaluate the samuraciclib-Orserdu combination in patients without a detectable ESR1-mutation and whether TP53 mutation status could be used to select patients for treatment.
Carrick, based in Boston, is also studying samuraciclib in combination with hormone therapy in HR-positive, HER2-negative breast cancer and evaluating it with Roche's SERD giredestrant, with Pfizer and Arvinas' estrogen receptor protein degrader vepdegestrant, and with the hormone therapy fulvestrant.
In 2021, the FDA granted fast-track designation to the samuraciclib-fulvestrant combination for advanced HR-positive, HER2-negative breast cancer patients whose cancers are resistant to CDK4/6 inhibitors.