Pfizer Inc. will submit a New Drug Application (NDA) with the United States Food and Drug Administration (FDA) for palbociclib, combined with letrozole, as first-line systemic treatment of post-menopausal women with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) locally advanced or metastatic breast cancer. Pfizer expects to submit the NDA early in the third quarter of this year. This decision was based on discussions with the FDA regarding the final results of PALOMA-1, a randomized, phase 2 trial comparing palbociclib plus letrozole versus letrozole alone in this population of patients.

Palbociclib received Breakthrough Therapy designation from the FDA in April 2013, for the first-line systemic treatment of women with advanced or metastatic ER+, HER2- breast cancer. This designation was based on interim data from the PALOMA-1 trial.

Palbociclib is an investigational oral targeted agent that selectively inhibits cyclin-dependent kinases (CDKs) 4 and 6 to regain cell cycle control and block tumor cell proliferation.

Loss of cell cycle control is a hallmark of cancer and CDK 4/6 are overactivated in numerous cancers, leading to loss of proliferative control. CDK 4/6 are key regulators of the cell cycle that trigger cellular progression from growth phase (G1) into phases associated with DNA replication (S). CDK 4/6, whose increased activity is frequent in estrogen receptor-positive (ER+) breast cancer (BC), are key downstream targets of ER signaling in ER+ BC. Preclinical data suggest that dual inhibition of CDK 4/6 and ER signaling is synergistic, and it has been shown to stop growth of ER+ BC cell lines in the G1 phase.

Palbociclib is not approved for any indication in any market.

PALOMA-1 (also known as Study 1003 and TRIO-18) is a phase 2 trial designed to assess progression-free survival in post-menopausal women with ER+, HER2- advanced breast cancer receiving palbociclib (125 mg once daily for three out of four weeks in repeated cycles) in combination with letrozole versus letrozole alone (2.5 mg once daily on a continuous regimen). Final results from PALOMA-1 were presented at the American Association for Cancer Research (AACR) Annual Meeting 2014. PALOMA-1 is conducted in collaboration with the Jonsson Cancer Center’s Revlon/UCLA Women’s Cancer Research Program, led by Dr. Dennis Slamon.

Pfizer has worked closely with investigators and international breast cancer experts to establish a robust development program for palbociclib in ER+, HER2- breast cancer across stages and treatment settings.

Pfizer has initiated two phase 3 studies of palbociclib in advanced/metastatic breast cancer. PALOMA-2 (also known as Study 1008) is a randomized (2:1), multi-center, double blind phase 3 study that evaluates palbociclib in combination with letrozole versus letrozole plus placebo as a first-line treatment for post-menopausal patients with ER+, HER2- advanced breast cancer. PALOMA-3 (also known as Study 1023) is a randomized (2:1), multi-center, double blind phase 3 study that evaluates palbociclib in combination with fulvestrant versus fulvestrant plus placebo in women with hormone receptor-positive (HR+), HER2- metastatic breast cancer whose disease has progressed after prior endocrine therapy.