Clinical trial NCT02734615: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced or Metastatic ER+ Breast Cancer
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-04-12
Enrollment: 199
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Incidence of dose limiting toxicities (DLTs)
timeFrame: Day 1 - Day 28 of Cycle 1 (28 day cycle)
measure: Safety and tolerability of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719
timeFrame: Approximately 3 years
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: Approximately 3 years
measure: Duration of Response (DOR)
timeFrame: 3 years
measure: Progression Free Survival (PFS)
timeFrame: 3 years
measure: Disease control rate (DCR)
timeFrame: 3 years
measure: Plasma concentration of study medications
timeFrame: 1 cycle (28 day cycle)
measure: Plasma concentration under fasted condition and fed condition
timeFrame: Up to 2 cycles (28 day cycle)
measure: Levels of Pharmacodynamic marker Estrogen receptor (ER)
timeFrame: 3 years
measure: Levels of Pharmacodynamic marker Progesterone receptor (PgR)
timeFrame: 3 years
measure: Levels of Pharmacodynamic marker pS6
timeFrame: 3 years
measure: Pharmacokinetics (PK) parameter AUC
timeFrame: 6 cycles (28 day cycle)
measure: PK parameter Cmax
timeFrame: 6 cycles (28 day cycle)
measure: PK parameter Tmax
timeFrame: 6 cycles (28 day cycle)
measure: PK parameter Cmin
timeFrame: 6 cycles (28 day cycle)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center SC - LSZ102X2101
state: Texas
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Lyon Cedex
country: France
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Koto ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Singapore
country: Singapore
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.