Clinical Trials /

Phase I/Ib Trial of LSZ102 Single Agent or LSZ102 + LEE011 or LSZ102 + BYL719 in ER+ Breast Cancers

NCT02734615

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

DrugSynonymsArms
LSZ102Arm A
LEE011ribociclib, KisqaliArm B
BYL719alpelisibArm C

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

NameTypeDescriptionInterventions
Arm AExperimentalPatients will get LSZ102 single agent during dose escalation.
  • LSZ102
Arm BExperimentalPatients will get LSZ102 in combination with LEE011 during dose escalation.
  • LSZ102
  • LEE011
Arm CExperimentalPatients will get LSZ102 in combination with BYL719 during dose escalation.
  • LSZ102
  • BYL719
Arm 1ExperimentalPatients will get LSZ102 single agent during dose expansion
  • LSZ102
Arm 2ExperimentalPatients will get LSZ102 + LEE011 (LEE011 intermittent regimen) during dose expansion
  • LSZ102
  • LEE011
Arm 3ExperimentalPatients will get LSZ102 + LEE011 (LEE011 continuous regimen) during dose expansion
  • LSZ102
  • LEE011
Arm 4ExperimentalPatient will get LSZ102 in combination with BYL719 during dose expansion
  • LSZ102
  • BYL719

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: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

October 15, 2019