ALPELISIB for Hormone receptor-positive HER2-negative advanced breast cancer

Inclusion criteria

• {"criterion_text":"- Participant is an adult ≥ 18 years old at the time of informed consent and has signed informed consent before any trial related activities and according to local guidelines.\n- Participant has a histologically and/or cytologically confirmed diagnosis of ER+ and/or PgR+ breast cancer by local laboratory.\n- Participant has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (Fluorescent in situ hybridization (FISH), Chromogenic in situ hybridization (CISH), or Silver-enhanced in situ hybridization (SISH)) test is required by local laboratory testing.\n- Participant has at least one measurable lesion as per RECIST v1.1 criteria as assessed by Investigator (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation).\n- Participant has recurrence or progression of disease during or after combined AI (i.e. letrozole, anastrozole, exemestane) and CDK4/6 inhibitor therapy. The combined AI and CDK4/6 inhibitor therapy does not need to be the latest treatment regimen (including adjuvant setting).\n- Participant has received ≤2 prior lines of systemic therapies overall in the metastatic setting, of which a maximum of 1 line of prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy) is permitted.\n- The presence of PIK3CA mutation(s) determined in tumor tissue prior to enrollment either by a Novartis designated laboratory or in tumor tissue or plasma ctDNA by a local laboratory using a Food and Drug Administration (FDA)-approved PIK3CA Companion Diagnostics (CDx) test for alpelisib or the CE-IVD QIAGEN Therascreen® PIK3CA RGQ PCR test.\n- If female, then the participant must be in postmenopausal status"}

Exclusion criteria

• {"criterion_text":"- Participant with symptomatic visceral disease or any disease burden that makes the participant ineligible for endocrine therapy (ET) per the investigator's best judgment.\n- Participant who relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine/endocrine-based therapy with no treatment for metastatic disease\n- Participant has received prior treatment with fulvestrant, any oral selective estrogen receptor degrader (SERD), any Phosphatidylinositol-3-Kinase (PI3K), mammalian Target of Rapamycin (mTOR) or Protein Kinase B (AKT) inhibitor"}

Primary endpoints

• {"endpoint_text":"- Progression-free survival (PFS) based on BIRC assessments and using RECIST v1.1 criteria","definition_or_measurement_approach":"PFS assessed by Blinded Independent Review Committee (BIRC) using RECIST v1.1 criteria"}

Secondary endpoints

• {"endpoint_text":"- Overall survival","definition_or_measurement_approach":"Overall survival (OS) — time from randomization to death from any cause"}
• {"endpoint_text":"- Overall response rate (ORR) with confirmed response, clinical benefit rate (CBR) with confirmed response, duration of response (DOR) with confirmed response, and time to response (TTR) based on BIRC assessment and RECIST v1.1","definition_or_measurement_approach":"ORR, CBR, DOR, TTR assessed by BIRC using RECIST v1.1 criteria; responses must be confirmed"}
• {"endpoint_text":"- PFS based on BIRC assessment and using RECIST v1.1 criteria for participants by PIK3CA mutation status assessed in ctDNA at baseline","definition_or_measurement_approach":"PFS assessed by BIRC using RECIST v1.1, analyzed by baseline ctDNA PIK3CA mutation status"}
• {"endpoint_text":"- Incidence, type and severity of adverse events per CTCAE v4.03 criteria","definition_or_measurement_approach":"Adverse events recorded and graded according to CTCAE v4.03"}
• {"endpoint_text":"- Time to definitive deterioration of ECOG performance status from baseline","definition_or_measurement_approach":"Time from baseline to definitive deterioration in ECOG performance status"}
• {"endpoint_text":"- Time to definitive (10%) deterioration in the global health status/Quality of Life (QoL) and symptom scale scores of the EORTC QLQ-C30 Change from baseline in global health status/QoL and symptom scale scores of the EORTC QLQ-C30","definition_or_measurement_approach":"Patient-reported outcomes measured by EORTC QLQ-C30 (10% definitive deterioration) and other PRO instruments (EQ-5D-5L, BPI-SF referenced)"}
• {"endpoint_text":"- Time from randomization to objective tumour progression on next line treatment or death from any cause (PFS2)","definition_or_measurement_approach":"PFS2 defined as time from randomization to objective tumour progression on next-line treatment or death from any cause"}

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

IQVIA Limited

Name

Icon Clinical Research Limited

Name

Syneos Health Inc.

Name

Parexel International (IRL) Limited

Name

Navigate Biopharma Services Inc.

Responsibilities

Biomarker sample processing and Biomarker analysis on newly obtained or archival tumor biopsy and circulating DNA analysis

Name

Fisher Clinical Services UK Limited

Responsibilities

Destruction or returns for BYL719

Name

Eresearchtechnology Inc.

Responsibilities

Imaging, BIRC review

Third parties

• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Creapharm Clinical Supplies","duties_or_roles":"Drug distribution, storage, relabeling, return and destruction","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"RWS Life Sciences Inc.","duties_or_roles":"Translations of ePROs","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Navigate Biopharma Services Inc.","duties_or_roles":"Biomarker sample processing and Biomarker analysis on newly obtained or archival tumor biopsy and circulating DNA analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Fisher Clinical Services UK Limited","duties_or_roles":"Destruction or returns for BYL719","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Imaging, BIRC review","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"Provider of electronic devices and ePRO database for PRO questionnaires","organisation_type":"Non-Pharmaceutical company"}