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

Phase 1

Terminated

• Conditions: Advanced or Metastatic ER+ Breast Cancer
• Interventions: Drug: LSZ102; Drug: LEE011; Drug: BYL719

• Registration Number: NCT02734615
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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

Not available

Study Timeline

• Study First Submitted: 2016-03-23
• Study First Submitted QC: 2016-04-06
• Study First Posted: 2016-04-12
• Study Start: 2016-06-14
• Primary Completion: 2021-09-13
• Study Completion: 2021-09-13
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-28
• Last Update Posted: 2022-08-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 199

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B	LEE011	Patients will get LSZ102 in combination with LEE011 during dose escalation.
Arm B	LSZ102	Patients will get LSZ102 in combination with LEE011 during dose escalation.
Arm A	LSZ102	Patients will get LSZ102 single agent during dose escalation.
Arm C	LSZ102	Patients will get LSZ102 in combination with BYL719 during dose escalation.
Arm C	BYL719	Patients will get LSZ102 in combination with BYL719 during dose escalation.
Arm 1	LSZ102	Patients will get LSZ102 single agent during dose expansion
Arm 2	LSZ102	Patients will get LSZ102 + LEE011 (LEE011 intermittent regimen) during dose expansion
Arm 2	LEE011	Patients will get LSZ102 + LEE011 (LEE011 intermittent regimen) during dose expansion
Arm 3	LSZ102	Patients will get LSZ102 + LEE011 (LEE011 continuous regimen) during dose expansion
Arm 3	LEE011	Patients will get LSZ102 + LEE011 (LEE011 continuous regimen) during dose expansion
Arm 4	LSZ102	Patient will get LSZ102 in combination with BYL719 during dose expansion
Arm 4	BYL719	Patient will get LSZ102 in combination with BYL719 during dose expansion

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719	Approximately 3 years	Incidence and severity of adverse events, serious adverse events, clinical laboratory values, vital signs, ECGs, dose interruptions, dose reductions and dose intensity.
Incidence of dose limiting toxicities (DLTs)	Day 1 - Day 28 of Cycle 1 (28 day cycle)	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

Name	Time	Method
Disease control rate (DCR)	3 years	Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719
Plasma concentration under fasted condition and fed condition	Up to 2 cycles (28 day cycle)	Plasma concentration versus time under fasted and fed conditions
Duration of Response (DOR)	3 years	Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719
Progression Free Survival (PFS)	3 years	Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719
Plasma concentration of study medications	1 cycle (28 day cycle)	Plasma concentration versus time
PK parameter Cmin	6 cycles (28 day cycle)	Cmin = Minimum observed plasma concentration after drug administration
Overall response rate (ORR)	Approximately 3 years	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.
Levels of Pharmacodynamic marker Progesterone receptor (PgR)	3 years	To assess the pharmacodynamic effect
Levels of Pharmacodynamic marker Estrogen receptor (ER)	3 years	To assess pharmacodynamics effect
Levels of Pharmacodynamic marker pS6	3 years	To assess the pharmacodynamic effect
Pharmacokinetics (PK) parameter AUC	6 cycles (28 day cycle)	AUC = Area under curve
PK parameter Cmax	6 cycles (28 day cycle)	Cmax = Maximum observed plasma concentration after drug administration
PK parameter Tmax	6 cycles (28 day cycle)	Tmax = Time to reach Cmax

Trial Locations

Locations (4)

MD Anderson Cancer Center SC - LSZ102X2101; 🇺🇸 Houston, Texas, United States

Massachusetts General Hospital Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Novartis Investigative Site; 🇸🇬 Singapore, Singapore