Description:
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.
Title
- Brief Title: Phase I/Ib Trial of LSZ102 Single Agent or LSZ102 + LEE011 or LSZ102 + BYL719 in ER+ Breast Cancers
- Official Title: A Phase I/Ib, Open Label Study of LSZ102 Single Agent and LSZ102 in Combination With Either LEE011 (LSZ102 + LEE011) or BYL719 (LSZ102 + BYL719) in Patients With Advanced or Metastatic ER+ Breast Cancer Who Have Progressed After Endocrine Therapy
Clinical Trial IDs
- ORG STUDY ID:
CLSZ102X2101
- SECONDARY ID:
2015-004016-38
- NCT ID:
NCT02734615
Conditions
- Advanced or Metastatic ER+ Breast Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| LSZ102 | | Arm 1 |
| LEE011 | ribociclib, Kisqali | Arm 2 |
| BYL719 | alpelisib | Arm 4 |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 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 | |
| Arm 4 | Experimental | Patient will get LSZ102 in combination with BYL719 during dose expansion | |
Eligibility Criteria
Inclusion Criteria:
- Written informed consent must be obtained prior to any procedures
- Histologically and/or cytologically confirmed diagnosis of ER+/HER2- breast cancer
- Advanced or metastatic breast cancer
- Must be able to swallow tablets and capsules
Exclusion Criteria:
- Symptomatic CNS metastases
- Patients whose laboratory values do not meet protocol criteria
- Clinically significant cardiac disease
- Impaired gastrointestinal function (GI) or GI disease that may significantly alter the
absorption of oral medications
Other protocol defined inclusion/exclusion criteria may apply.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Incidence of dose limiting toxicities (DLTs) |
| Time Frame: | Day 1 - Day 28 of Cycle 1 (28 day cycle) |
| Safety Issue: | |
| Description: | 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. |
Secondary Outcome Measures
| Measure: | Overall response rate (ORR) |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Duration of Response (DOR) |
| Time Frame: | 3 years |
| Safety Issue: | |
| Description: | Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719 |
| Measure: | Progression Free Survival (PFS) |
| Time Frame: | 3 years |
| Safety Issue: | |
| Description: | Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719 |
| Measure: | Disease control rate (DCR) |
| Time Frame: | 3 years |
| Safety Issue: | |
| Description: | Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719 |
| Measure: | Plasma concentration of study medications |
| Time Frame: | 1 cycle (28 day cycle) |
| Safety Issue: | |
| Description: | Plasma concentration versus time |
| Measure: | Plasma concentration under fasted condition and fed condition |
| Time Frame: | Up to 2 cycles (28 day cycle) |
| Safety Issue: | |
| Description: | Plasma concentration versus time under fasted and fed conditions |
| Measure: | Levels of Pharmacodynamic marker Estrogen receptor (ER) |
| Time Frame: | 3 years |
| Safety Issue: | |
| Description: | To assess pharmacodynamics effect |
| Measure: | Levels of Pharmacodynamic marker Progesterone receptor (PgR) |
| Time Frame: | 3 years |
| Safety Issue: | |
| Description: | To assess the pharmacodynamic effect |
| Measure: | Levels of Pharmacodynamic marker pS6 |
| Time Frame: | 3 years |
| Safety Issue: | |
| Description: | To assess the pharmacodynamic effect |
| Measure: | Pharmacokinetics (PK) parameter AUC |
| Time Frame: | 6 cycles (28 day cycle) |
| Safety Issue: | |
| Description: | AUC = Area under curve |
| Measure: | PK parameter Cmax |
| Time Frame: | 6 cycles (28 day cycle) |
| Safety Issue: | |
| Description: | Cmax = Maximum observed plasma concentration after drug administration |
| Measure: | PK parameter Tmax |
| Time Frame: | 6 cycles (28 day cycle) |
| Safety Issue: | |
| Description: | Tmax = Time to reach Cmax |
| Measure: | PK parameter Cmin |
| Time Frame: | 6 cycles (28 day cycle) |
| Safety Issue: | |
| Description: | Cmin = Minimum observed plasma concentration after drug administration |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- LSZ102
- LEE011
- ribociclib
- Kisqali
- BYL719
- alpelisib
- ER+ breast cancer
- advanced ER+ breast cancer
- metastatic ER+ breast cancer
- SERD
- SERM
- fulvestrant
- tamoxifen
- aromatase inhibitor
- ESR1
- mtESR1
- wtESR1
- estrogen receptor
- endocrine therapy
Last Updated
June 22, 2021
