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The purpose of the Phase Ib is to:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LEE011 +Letrozole | Experimental | LEE011 - 3 weeks on 1 week off Letrozole 2.5mg - Once daily |
|
| LEE011 + Tamoxifen | Experimental | LEE011 - 3 weeks on 1 week off Tamoxifen 20mg - Once daily |
|
| LEE011 + Fulvestrant | Experimental | LEE011 - 3 weeks on 1 week off Fulvestrant 500 mg - Dosed every 28 days (Day 1 for each cycle) with 1 additional dose on Day 15 of Cycle 1 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LEE011 | Drug | LEE011 as 50 mg and 200 mg hard gelatin oral capsules as individual patient supply packaged in bottles. LEE011 will be taken QD - days 1-21 of each 28 days cycle. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Phase Ib Dose escalation - Frequency of dose limiting toxicities (DLTs) | DLTs at each dose level associated with administration of LEE011 and letrozole | first cycle (28 days) |
| Phase Ib Dose Expansion: Number of participants with adverse events (AEs) | This will be defined by changes in hematology and chemistry values, vital signs and ECGs, frequency and duration of AEs, lab abnormalities and other safety parameters. For LEE011 and letrozole or tamoxifen or fulvestrant | 18 months |
| Phase Ib Dose Expansion: Number of participants with serious adverse events (SAEs) | This will be defined by changes in hematology and chemistry values, vital signs and ECGs, frequency and duration of SAEs, lab abnormalities and other safety parameters. For LEE011 and letrozole or tamoxifen or fulvestrant | 18 months |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with adverse events (AEs) - Phase Ib dose escalation | This will be defined by changes in hematology and chemistry values, vital signs and ECGs, frequency and duration of AEs, lab abnormalities and other safety parameters. For LEE011 and letrozole or tamoxifen or fulvestrant | 18 months |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Hong Kong | Hong Kong | ||||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37580773 | Derived | Chiu 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. | |
| 32619077 | Derived |
| Label | URL |
|---|---|
| Related Info | View source |
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| Letrozole | Drug | 25mg |
|
| Tamoxifen | Drug | 20 mg |
|
| Fulvestrant | Drug | 500 mg |
|
| goserelin | Drug |
|
| Number of participants with serious adverse events (SAEs) - Phase Ib dose escalation |
This will be defined by changes in hematology and chemistry values, vital signs and ECGs, frequency and duration of SAEs, lab abnormalities and other safety parameters. For LEE011 and letrozole or tamoxifen or fulvestrant |
| 18 months |
| Overall Response Rate (ORR) - Phase Ib dose expansion | Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant | 18 months |
| Clinical Benefit Rate (CBR) - Phase Ib dose expansion | Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant | 18 months |
| Composite Plasma pharmacokinetics (PK) parameters of LEE011 (and relevant metabolites) and letrozole - Phase Ib | As assessed by PK parameters such as Cmax, Tmax, AUC0-24hours, accumulation ratio and Ctrough for LEE011 (and relevant metabolites) and letrozole, tamoxifen and fulvestrant | C1D1, C1D2, C1D8, C1D15, C1D21, C1D22, C2D15, C3D15 |
| Progression Free Survival (PFS) as per RECIST v1.1- phase Ib dose expansion | Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant | 18 months |
| Overall Survival (OS) - Phase Ib dose expansion | Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant | 18 months |
| Disease Control Rate (DCR) - Phase Ib dose expansion | Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant | 18 months |
| Duration of Response (DOR) - Phase Ib dose expansion | Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant | 18 months |
| Nagoya |
| Aichi-ken |
| 467-8602 |
| Japan |
| Novartis Investigative Site | Sapporo | Hokkaido | 003-0804 | Japan |
| Novartis Investigative Site | Yokohama | Kanagawa | 241-8515 | Japan |
| Novartis Investigative Site | Osaka | Osaka | 540-0006 | Japan |
| Novartis Investigative Site | Suita | Osaka | 565 0871 | Japan |
| Novartis Investigative Site | Hidaka | Saitama | 350-1298 | Japan |
| Novartis Investigative Site | Kitaadachi-gun | Saitama | 362-0806 | Japan |
| Novartis Investigative Site | Sunto Gun | Shizuoka | 411 8777 | Japan |
| Novartis Investigative Site | Bunkyo Ku | Tokyo | 113-8431 | Japan |
| Novartis Investigative Site | Bunkyo Ku | Tokyo | 113-8677 | Japan |
| Novartis Investigative Site | Koto Ku | Tokyo | 135 8550 | Japan |
| Novartis Investigative Site | Shinagawa-ku | Tokyo | 142-8666 | Japan |
| Novartis Investigative Site | Shinjuku-ku | Tokyo | 160-0023 | Japan |
| Novartis Investigative Site | Singapore | 168583 | Singapore |
| Yap 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. |
| ID | Term |
|---|---|
| C000589651 | ribociclib |
| D000077289 | Letrozole |
| D013629 | Tamoxifen |
| D000077267 | Fulvestrant |
| D017273 | Goserelin |
| ID | Term |
|---|---|
| D009570 | Nitriles |
| D009930 | Organic Chemicals |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004958 | Estradiol |
| D004963 | Estrenes |
| D004962 | Estranes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D007987 | Gonadotropin-Releasing Hormone |
| D010906 | Pituitary Hormone-Releasing Hormones |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
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