TIP103 Randomized Phase 3 Clinical Trial Evaluating Atirmociclib Plus Letrozole Versus a CDK4/6 Inhibitor Plus Letrozole as First-Line Treatment for Patients With HR+/HER2− Advanced/Metastatic Breast Cancer

Background

CDK4/6 inhibitors, in combination with endocrine therapy, have improved survival outcomes when used as first-line treatment for patients with hormone receptor–positive (HR+)/HER2-negative (HER2–) advanced or metastatic breast cancer. However, there is still a need for more effective and tolerable treatment options. Atirmociclib (PF-07220060) is an oral, potent, and selective CDK4 inhibitor, with sparing of CDK6. An ongoing first-in-human phase 1/2a study has reported promising data of efficacy, safety, and tolerability of atirmociclib plus endocrine therapy in patients with HR+/HER2– advanced breast cancer.

Methods

This international, open-label, randomized, multicenter phase 3 trial is evaluating atirmociclib plus letrozole vs a CDK4/6 inhibitor plus letrozole in adults (≥18 years) with HR+/HER2− advanced breast cancer with no prior systemic anticancer treatment for their advanced breast cancer. Additional inclusion criteria include measurable disease or non-measurable bone-only disease, and an ECOG performance status of 2 or less. Patients with recurrence during or within 12 months after the last dose of prior (neo)adjuvant endocrine therapy or CDK4/6 inhibitor will be excluded. Approximately 1020 patients will be randomly assigned (1:1) to receive either atirmociclib (300 mg by mouth twice daily (PO BID), continuously in 28-day cycles) plus letrozole (2.5 mg PO QD) or investigator’s choice of a CDK4/6 inhibitor plus letrozole. Patients will be stratified by disease site, de novo advanced/metastatic disease, and investigator’s intended choice of CDK4/6 inhibitor. No crossover to experimental therapy is permitted in the control group. The primary end point is progression-free survival by blinded independent central review (BICR), defined as the time from randomization to first documented objective disease progression as determined by BICR per RECIST v1.1 or death due to any cause, whichever occurs first. Overall survival is a key secondary end point; other secondary endpoints include objective response, duration of response, clinical benefit rate, safety, patient-reported outcomes, and changes in circulating tumor DNA. Enrollment is ongoing in the US, Europe and Asia, with additional global sites planned (NCT06760637).

ClinicalTrials.gov Identifier: NCT06760637

Funding source: This study is sponsored by Pfizer Inc.

Acknowledgments: Medical writing support was provided by Diana Avery, PhD, of Oxford PharmaGenesis Inc., Wilmington, DE, USA, and was funded by Pfizer Inc.