A Phase Ib Dose Escalation Study of the Combination of LEE011 With Letrozole and Dose Expansion of LEE011 With Hormonal Therapy for the Treatment of Pre-(With Goserelin) and Postmenopausal Women With Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer

The purpose of the Phase Ib is to: 1. determine the recommended dose of LEE011 in combination with a standard dose of letrozole as well as to provide additional safety and anti-tumor activity data in Asian non-Japanese patients 2. determine the recommended dose of LEE011 in combination with a standard dose of letrozole as well as to provide additional safety and activity data in Japanese patients 3. evaluate the safety and anti-tumor activity of LEE011 at the RP2D established in the dose escalation part in combination with a standard dose of letrozole, fulvestrant or tamoxifen plus goserelin in Japanese patients.

Sex

Female

Minimum age

18 Years

Inclusion Criteria:

* Women with advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy (surgery and/or radiotherapy).
* Patient has a histologically and/or cytologically confirmed diagnosis of estrogen receptor positive and/or progesterone receptor positive breast cancer
* Patient has HER2-negative breast cancer
* Patient has adequate bone marrow and organ function

Exclusion Criteria:

* Patient who received any CDK4/6 inhibitor.
* Patient has a known hypersensitivity to any of the excipients of LEE011 or letrozole
* Patients with inflammatory breast cancer.
* Patient who received any prior systemic anti-cancer therapy (including hormonal therapy and chemotherapy) for advanced breast cancer
* Patient is currently using other anti-cancer therapy
* Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects.
* Patient who has received radiotherapy ≤ 4 weeks
* Patient has a concurrent malignancy or malignancy within 3 years
* Patient has metastases to the central nervous system (CNS).
* Patient has a known history of HIV infection

Other protocol-defined inclusion/exclusion criteria may apply

• DERIVEDChiu J, Su F, Joshi M, Masuda N, Ishikawa T, Aruga T, Zarate JP, Babbar N, Balbin OA, Yap YS. Potential value of ctDNA monitoring in metastatic HR + /HER2 - breast cancer: longitudinal ctDNA analysis in the phase Ib MONALEESASIA trial. BMC Med. 2023 Aug 15;21(1):306. doi: 10.1186/s12916-023-03017-z. PMID 37580773
• DERIVEDYap YS, Chiu J, Ito Y, Ishikawa T, Aruga T, Kim SJ, Toyama T, Saeki T, Saito M, Gounaris I, Su F, Ji Y, Han Y, Gazdoiu M, Masuda N. Ribociclib, a CDK 4/6 inhibitor, plus endocrine therapy in Asian women with advanced breast cancer. Cancer Sci. 2020 Sep;111(9):3313-3326. doi: 10.1111/cas.14554. Epub 2020 Jul 28. PMID 32619077