Advanced or Metastatic ER+ Breast CancerPhase 1NCT02734615
Phase I/Ib Trial of LSZ102 Single Agent or LSZ102 + LEE011 or LSZ102 + BYL719 in ER+ Breast Cancers
A Phase 1 study testing LSZ102, LEE011 and BYL719 in people with Advanced or Metastatic ER+ Breast Cancer, run by Novartis Pharmaceuticals at 10 sites in 7 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced or Metastatic ER+ Breast Cancer
- What is being tested?
- LSZ102, LEE011 and BYL719
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 199 participants
- Where
- 10 sitesin 7 countries
- Study dates
- 14 Jun 2016to 13 Sep 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
10 sites in 7 countries.
10 sites in 7 countries
United States3 sites
Massachusetts General Hospital Massachusetts General Hospital
Boston, Massachusetts, 02114
MD Anderson Cancer Center SC - LSZ102X2101
Houston, Texas, 77030
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Italy2 sites
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Milan, MI, 20141
About this study
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
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
- Being tested
- LSZ102, LEE011, BYL719
- 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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LSZ102Drug
LSZ102
LEE011Drug
Also called ribociclib, Kisqali
LEE011
BYL719Drug
Also called alpelisib
BYL719
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Patients will get LSZ102 single agent during dose escalation. Receives: Drug: LSZ102 |
| Arm B | Experimental | Patients will get LSZ102 in combination with LEE011 during dose escalation. Receives: Drug: LSZ102; Drug: LEE011 |
| Arm C | Experimental | Patients will get LSZ102 in combination with BYL719 during dose escalation. Receives: Drug: LSZ102; Drug: BYL719 |
| Arm 1 | Experimental | Patients will get LSZ102 single agent during dose expansion Receives: Drug: LSZ102 |
| Arm 2 | Experimental | Patients will get LSZ102 + LEE011 (LEE011 intermittent regimen) during dose expansion Receives: Drug: LSZ102; Drug: LEE011 |
| Arm 3 | Experimental | Patients will get LSZ102 + LEE011 (LEE011 continuous regimen) during dose expansion Receives: Drug: LSZ102; Drug: LEE011 |
| Arm 4 | Experimental | Patient will get LSZ102 in combination with BYL719 during dose expansion Receives: Drug: LSZ102; Drug: BYL719 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Approximately 3 years
Secondary outcomes (13)
Overall response rate (ORR)
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.
Measured: Approximately 3 years
Duration of Response (DOR)
Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719
Measured: 3 years
Progression Free Survival (PFS)
Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719
Measured: 3 years
Disease control rate (DCR)
Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719
Measured: 3 years
Plasma concentration of study medications
Plasma concentration versus time
Measured: 1 cycle (28 day cycle)
Plasma concentration under fasted condition and fed condition
Plasma concentration versus time under fasted and fed conditions
Measured: Up to 2 cycles (28 day cycle)
Levels of Pharmacodynamic marker Estrogen receptor (ER)
To assess pharmacodynamics effect
Measured: 3 years
Levels of Pharmacodynamic marker Progesterone receptor (PgR)
To assess the pharmacodynamic effect
Measured: 3 years
Levels of Pharmacodynamic marker pS6
To assess the pharmacodynamic effect
Measured: 3 years
Pharmacokinetics (PK) parameter AUC
AUC = Area under curve
Measured: 6 cycles (28 day cycle)
PK parameter Cmax
Cmax = Maximum observed plasma concentration after drug administration
Measured: 6 cycles (28 day cycle)
PK parameter Tmax
Tmax = Time to reach Cmax
Measured: 6 cycles (28 day cycle)
PK parameter Cmin
Cmin = Minimum observed plasma concentration after drug administration
Measured: 6 cycles (28 day cycle)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2016 (estimated)
- Study start14 Jun 2016
- Primary completion13 Sep 2021
- Study completion13 Sep 2021
Why it stopped: Sponsor's decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced or Metastatic ER+ Breast CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 199 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02734615
- Sponsor's protocol ID
- CLSZ102X2101
- Other IDs
- 2015-004016-38, 2015
- Status last verified
- Jul 2022
- First submitted
- 23 Mar 2016
- Last updated
- 1 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34433648
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02734615
- Acronym / sponsor ID
- CLSZ102X2101
- Conditions
- Advanced or Metastatic ER+ Breast Cancer
- Keywords
- LSZ102, LEE011, ribociclib, Kisqali, BYL719, alpelisib, ER+ breast cancer, advanced ER+ breast cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor's decision
- Enrolment
- 199 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 14 Jun 2016 (actual)
- Primary completion
- 13 Sep 2021 (actual)
- Study completion
- 13 Sep 2021 (actual)
- First posted
- 12 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: LSZ102Patients will get LSZ102 single agent during dose escalation. |
| Arm B | Experimental | Drug: LSZ102, Drug: LEE011Patients will get LSZ102 in combination with LEE011 during dose escalation. |
| Arm C | Experimental | Drug: LSZ102, Drug: BYL719Patients will get LSZ102 in combination with BYL719 during dose escalation. |
| Arm 1 | Experimental | Drug: LSZ102Patients will get LSZ102 single agent during dose expansion |
| Arm 2 | Experimental | Drug: LSZ102, Drug: LEE011Patients will get LSZ102 + LEE011 (LEE011 intermittent regimen) during dose expansion |
| Arm 3 | Experimental | Drug: LSZ102, Drug: LEE011Patients will get LSZ102 + LEE011 (LEE011 continuous regimen) during dose expansion |
| Arm 4 | Experimental | Drug: LSZ102, Drug: BYL719Patient will get LSZ102 in combination with BYL719 during dose expansion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LSZ102LSZ102 | Drug | Arm 1, Arm 2, Arm 3, Arm 4, Arm A, Arm B, Arm C |
| LEE011Also: ribociclib, KisqaliLEE011 | Drug | Arm 2, Arm 3, Arm B |
| BYL719Also: alpelisibBYL719 | Drug | Arm 4, Arm C |
Primary outcome
Incidence of dose limiting toxicities (DLTs)
Time frame: 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.
Safety and tolerability of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719
Time frame: 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.
13 secondary outcomes
Overall response rate (ORR)
Time frame: Approximately 3 years
Duration of Response (DOR)
Time frame: 3 years
Progression Free Survival (PFS)
Time frame: 3 years
Disease control rate (DCR)
Time frame: 3 years
Plasma concentration of study medications
Time frame: 1 cycle (28 day cycle)
Plasma concentration under fasted condition and fed condition
Time frame: Up to 2 cycles (28 day cycle)
Levels of Pharmacodynamic marker Estrogen receptor (ER)
Time frame: 3 years
Levels of Pharmacodynamic marker Progesterone receptor (PgR)
Time frame: 3 years
Levels of Pharmacodynamic marker pS6
Time frame: 3 years
Pharmacokinetics (PK) parameter AUC
Time frame: 6 cycles (28 day cycle)
PK parameter Cmax
Time frame: 6 cycles (28 day cycle)
PK parameter Tmax
Time frame: 6 cycles (28 day cycle)
PK parameter Cmin
Time frame: 6 cycles (28 day cycle)
Results and safety
The study was stopped early (reason given: Sponsor's decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2022.
- Results publication: PubMed 34433648Jhaveri 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.
- Study ResultsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
10 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LSZ102, LEE011 and BYL719 in people with Advanced or Metastatic ER+ Breast Cancer, run by Novartis Pharmaceuticals at 10 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Italy, Belgium, France, Germany and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor's decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose limiting toxicities (DLTs) (time frame: Day 1 - Day 28 of Cycle 1 (28 day cycle)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02734615, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2022.