Novel CDK2/4 Inhibitor Under Study in Metastatic Breast Cancer

By: Vanessa A. Carter, BS
Posted: Tuesday, October 22, 2024

Timothy Anthony Yap, MBBS, PhD, FRCP, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues conducted a first-in-class novel combination trial of the next-generation CDK2-selective inhibitor PF-07104091 and the CDK4-selective inhibitor PF-07220060—now known as atirmociclib—in patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer. Presented during the European Society for Medical Oncology (ESMO) Congress 20224 (Abstract 618MO), the results of this trial indicate this treatment combination has antitumor activity.

“In 26 heavily pretreated patients with metastatic breast cancer, the objective response rate was 27.8%, the disease control rate was 55.6%, and the median progression-free survival was 8.3 months,” Dr. Yap stated in an institutional press release. “The combination was well tolerated and had a manageable safety profile overall, with neutropenia being the most common grade 3 or higher adverse event. Dose-expansion arms of the trial are ongoing.”

This phase Ib/II trial administered various dose combinations of atirmociclib/PF-07104091 (100/225 mg, 200/75 mg, 200/150 mg, 300/75 mg, 300/150 mg), twice daily in 28-day cycles, to 33 patients with HR-positive, HER2-negative metastatic breast cancer (n = 26) and advanced solid tumors (n = 7). At cycle 3, patients were allowed to receive fulvestrant.

All but one patient in the intent-to-treat cohort reported treatment-emergent adverse events, the majority of which were grade 3 or higher (63.6%); neutropenia (66.7%), nausea (66.7%), and diarrhea (63.6%) were the most common. Discontinuation of treatment was reported in one patient because of treatment-related adverse events. Dose-limiting toxicities were uncommon, affecting two patients on 200/150 mg and three patients on 300/150 mg.

Using the safety data, the two recommended doses for expansion are 100/225 mg and 300/75 mg of atirmociclib/PF-07104091, twice daily, and in combination with endocrine therapy. Of 18 patients with measurable disease, 5 had a partial response with a duration of response up to 12.1 months, and 5 had stable disease.

Disclosure: For full disclosures of the study authors, visit cslide.ctimeetingtech.com.

ESMO Congress 2024

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