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

NCT02734615 | Terminated Phase 1 FDA Drug

• 2 other identifiers: CLSZ102X21012015-004016-38
• Study Type: interventional
• Target: 199
• Locations: 7 countries
• Sites: 10

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.

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

Outcome Measures

Primary Outcomes (2)

• Incidence of dose limiting toxicities (DLTs)

  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.

  Day 1 - Day 28 of Cycle 1 (28 day cycle)

• Safety and tolerability of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719

  Incidence and severity of adverse events, serious adverse events, clinical laboratory values, vital signs, ECGs, dose interruptions, dose reductions and dose intensity.

  Approximately 3 years

Secondary Outcomes (13)

• Overall response rate (ORR)

  Approximately 3 years

• Duration of Response (DOR)

  3 years

• Progression Free Survival (PFS)

  3 years

• Disease control rate (DCR)

  3 years

• Plasma concentration of study medications

  1 cycle (28 day cycle)

Study Arms (7)

Arm A

EXPERIMENTAL

Patients will get LSZ102 single agent during dose escalation.

Drug: LSZ102

Arm B

EXPERIMENTAL

Patients will get LSZ102 in combination with LEE011 during dose escalation.

Drug: LSZ102; Drug: LEE011

Arm C

EXPERIMENTAL

Patients will get LSZ102 in combination with BYL719 during dose escalation.

Drug: LSZ102; Drug: BYL719

Arm 1

EXPERIMENTAL

Patients will get LSZ102 single agent during dose expansion

Drug: LSZ102

Arm 2

EXPERIMENTAL

Patients will get LSZ102 + LEE011 (LEE011 intermittent regimen) during dose expansion

Drug: LSZ102; Drug: LEE011

Arm 3

EXPERIMENTAL

Patients will get LSZ102 + LEE011 (LEE011 continuous regimen) during dose expansion

Drug: LSZ102; Drug: LEE011

Arm 4

EXPERIMENTAL

Patient will get LSZ102 in combination with BYL719 during dose expansion

Drug: LSZ102; Drug: BYL719

Interventions

LSZ102 DRUG

LSZ102

Arm 1; Arm 2; Arm 3; Arm 4; Arm A; Arm B; Arm C

LEE011 DRUG

LEE011

Also known as: ribociclib, Kisqali

Arm 2; Arm 3; Arm B

BYL719 DRUG

BYL719

Also known as: alpelisib

Arm 4; Arm C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (10)

Massachusetts General Hospital Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MD Anderson Cancer Center SC - LSZ102X2101

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Brussels, 1200, Belgium

Location

Novartis Investigative Site

Lyon, 69373, France

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Milan, MI, 20141, Italy

Location

Novartis Investigative Site

Koto Ku, Tokyo, 135 8550, Japan

Location

Novartis Investigative Site

Singapore, 169610, Singapore

Location

Related Publications (1)

• 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.

  PMID: 34433648 RESULT

Related Links

• Study Results

MeSH Terms

Interventions

LSZ102; ribociclib; Alpelisib

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2016
• First Posted: April 12, 2016
• Study Start: June 14, 2016
• Primary Completion: September 13, 2021
• Study Completion: September 13, 2021
• Last Updated: August 1, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2); US (3); FR (1); DE (1); JP (1); BE (1); SG (1)