Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2015-004016-38 | EudraCT Number |
Not provided
Not provided
Not provided
Sponsor's decision
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
To characterize the safety and tolerability, identify recommended doses and regimens for future studies, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of LSZ102 as a single agent and in combination with either LEE011 or BYL719 in adult patients with locally advanced or metastatic ER+ breast cancer who have progressed after endocrine therapy.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A | Experimental | Patients will get LSZ102 single agent during dose escalation. |
|
| Arm B | Experimental | Patients will get LSZ102 in combination with LEE011 during dose escalation. |
|
| Arm C | Experimental | Patients will get LSZ102 in combination with BYL719 during dose escalation. |
|
| Arm 1 | Experimental | Patients will get LSZ102 single agent during dose expansion |
|
| Arm 2 | Experimental | Patients will get LSZ102 + LEE011 (LEE011 intermittent regimen) during dose expansion |
|
| Arm 3 | Experimental | Patients will get LSZ102 + LEE011 (LEE011 continuous regimen) during dose expansion |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LSZ102 | Drug | LSZ102 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of dose limiting toxicities (DLTs) | The dose escalation part of the study will be guided by well-established statistical methods/models to estimate the maximum tolerated doses (MTD)and/or recommended doses for expansion (RDE). Safety, pharmacokinetic and pharmacodynamics data will guide dose escalation decisions. | Day 1 - Day 28 of Cycle 1 (28 day cycle) |
| Safety and tolerability of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719 | Incidence and severity of adverse events, serious adverse events, clinical laboratory values, vital signs, ECGs, dose interruptions, dose reductions and dose intensity. | Approximately 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Overall response rate (ORR) | Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719. ORR is defined as the proportion of patients with a best overall response of complete response or partial response. | Approximately 3 years |
| Duration of Response (DOR) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Other protocol defined inclusion/exclusion criteria may apply.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34433648 | Result | Jhaveri K, Juric D, Yap YS, Cresta S, Layman RM, Duhoux FP, Terret C, Takahashi S, Huober J, Kundamal N, Sheng Q, Balbin A, Ji Y, He W, Crystal A, De Vita S, Curigliano G. A Phase I Study of LSZ102, an Oral Selective Estrogen Receptor Degrader, with or without Ribociclib or Alpelisib, in Patients with Estrogen Receptor-Positive Breast Cancer. Clin Cancer Res. 2021 Nov 1;27(21):5760-5770. doi: 10.1158/1078-0432.CCR-21-1095. Epub 2021 Aug 25. |
| Label | URL |
|---|---|
| Study Results | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Arm 4 | Experimental | Patient will get LSZ102 in combination with BYL719 during dose expansion |
|
| LEE011 | Drug | LEE011 |
|
|
| BYL719 | Drug | BYL719 |
|
|
Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719 |
| 3 years |
| Progression Free Survival (PFS) | Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719 | 3 years |
| Disease control rate (DCR) | Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719 | 3 years |
| Plasma concentration of study medications | Plasma concentration versus time | 1 cycle (28 day cycle) |
| Plasma concentration under fasted condition and fed condition | Plasma concentration versus time under fasted and fed conditions | Up to 2 cycles (28 day cycle) |
| Levels of Pharmacodynamic marker Estrogen receptor (ER) | To assess pharmacodynamics effect | 3 years |
| Levels of Pharmacodynamic marker Progesterone receptor (PgR) | To assess the pharmacodynamic effect | 3 years |
| Levels of Pharmacodynamic marker pS6 | To assess the pharmacodynamic effect | 3 years |
| Pharmacokinetics (PK) parameter AUC | AUC = Area under curve | 6 cycles (28 day cycle) |
| PK parameter Cmax | Cmax = Maximum observed plasma concentration after drug administration | 6 cycles (28 day cycle) |
| PK parameter Tmax | Tmax = Time to reach Cmax | 6 cycles (28 day cycle) |
| PK parameter Cmin | Cmin = Minimum observed plasma concentration after drug administration | 6 cycles (28 day cycle) |
| Memorial Sloan Kettering Cancer Center |
| New York |
| New York |
| 10065 |
| United States |
| MD Anderson Cancer Center SC - LSZ102X2101 | Houston | Texas | 77030 | United States |
| Novartis Investigative Site | Brussels | 1200 | Belgium |
| Novartis Investigative Site | Lyon | 69373 | France |
| Novartis Investigative Site | Ulm | 89081 | Germany |
| Novartis Investigative Site | Milan | MI | 20133 | Italy |
| Novartis Investigative Site | Milan | MI | 20141 | Italy |
| Novartis Investigative Site | Koto Ku | Tokyo | 135 8550 | Japan |
| Novartis Investigative Site | Singapore | 169610 | Singapore |
| ID | Term |
|---|---|
| C000712982 | LSZ102 |
| C000589651 | ribociclib |
| C585539 | Alpelisib |
Not provided
Not provided
Not provided