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

Trial Conditions

  • Advanced or Metastatic ER+ Breast Cancer

Trial Interventions

DrugSynonymsArms
LSZ102Arm A
LEE011ribociclibArm B
BYL719alpelisibArm C

Trial 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.

Detailed Description

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 1aExperimentalPatients with wildtype ESR1 genes will get LSZ102 single agent during dose expansion.
      • LSZ102
        Arm 1bExperimentalPatients with mutant ESR1 genes will get LSZ102 single agent during dose expansion.
        • LSZ102

          Eligibility Criteria

          Inclusion Criteria:

          - Written informed consent must be obtained prior to any procedures

          - Histologically and/or cytologically confirmed diagnosis of ER+ breast cancer

          - Advanced or metastatic breast cancer

          - Objective evidence of either progression after endocrine therapy for metastatic or locally advanced disease OR recurrence while on, or within 12 months of the end of adjuvant treatment with letrozole or anastrozole

          - 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:Both
          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:Yes
          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:No
          Description:Assessment of preliminary anti-tumor activity of LSZ102. 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:No
          Description:Assessment of preliminary anti-tumor activity of LSZ102
          Measure:Progression Free Survival (PFS)
          Time Frame:3 years
          Safety Issue:No
          Description:Assessment of preliminary anti-tumor activity of LSZ102
          Measure:Disease control rate (DCR)
          Time Frame:3 years
          Safety Issue:No
          Description:Assessment of preliminary anti-tumor activity of LSZ102
          Measure:Plasma concentration of study medications
          Time Frame:1 cycle (28 day cycle)
          Safety Issue:No
          Description:Plasma concentration versus time
          Measure:Plasma concentration of LSZ102 under fasted condition and fed condition
          Time Frame:Up to 2 cycles (28 day cycle)
          Safety Issue:No
          Description:Plasma concentration versus time under fasted and fed conditions
          Measure:Levels of Pharmacodynamic marker Estrogen receptor (ER)
          Time Frame:3 years
          Safety Issue:No
          Description:To assess pharmacodynamics effect
          Measure:Levels of Pharmacodynamic marker Progesterone receptor (PR)
          Time Frame:3 years
          Safety Issue:No
          Description:To assess the pharmacodynamic effect
          Measure:Levels of Pharmacodynamic marker Ki67
          Time Frame:3 years
          Safety Issue:No
          Description:To assess pharmacodynamic effect
          Measure:Levels of Pharmacodynamic marker pAKT
          Time Frame:3 years
          Safety Issue:No
          Description:To assess the pharmacodynamic effect
          Measure:Levels of Pharmacodynamic marker pS6
          Time Frame:3 years
          Safety Issue:No
          Description:To assess the pharmacodynamic effect
          Measure:Pharmacokinetics (PK) parameter AUC
          Time Frame:6 cycles (28 day cycle)
          Safety Issue:No
          Description:AUC = Area under curve
          Measure:PK parameter Cmax
          Time Frame:6 cycles (28 day cycle)
          Safety Issue:No
          Description:Cmax = Maximum observed plasma concentration after drug administration
          Measure:PK parameter Tmax
          Time Frame:6 cycles (28 day cycle)
          Safety Issue:No
          Description:Tmax = Time to reach Cmax
          Measure:PK parameter Cmin
          Time Frame:6 cycles (28 day cycle)
          Safety Issue:No
          Description:Cmin = Minimum observed plasma concentration after drug administration

          Trial Keywords

          • LSZ102
          • ER+ breast cancer
          • advanced ER+ breast cancer
          • metastatic ER+ breast cancer
          • SERD
          • SERM
          • fulvestrant
          • tamoxifen
          • aromatase inhibitor
          • ESR1
          • estrogen receptor
          • endocrine therapy