marked.bio

PI3Kα inhibitor · small molecule

alpelisib

13 active trials across 5 of our biomarkers, targeting PI3Kα. 2 active approvals for a biomarker on marked.bio.

Also known as BYL719, Piqray.

Counts only trials that select patients by one of the biomarkers on marked.bio, not every trial of this drug.

Approvals and pivotal results

Biomarker-selected approvals in the United States and the European Union, with the pivotal trial's results and side effects where we have them. Results from different trials are not directly comparable.

TherapyBiomarkerTumourUnited StatesEuropean Union
alpelisib with fulvestrant
FDA, 2019
advanced or metastatic, PIK3CA-mutated, after endocrine therapy FDA approval 24/05/2019; companion test therascreen PIK3CA RGQ PCR Kit (tissue or plasma). Source
EU (EMA), 2020
locally advanced or metastatic, PIK3CA-mutated, after endocrine therapy as monotherapy EU marketing authorisation 27/07/2020. Source
Piqrayfulvestrant page 		PIK3CA activating mutation breast (HR+/HER2-) Approved 2019 Approved 2020

In the FDA approval summary

SOLAR-1 vs placebo + fulvestrant
PFS 11.0 months vs 5.7 months, HR 0.65 (0.50-0.85)

Trial details and side effects
Patients
PIK3CA-mutant cohort, HR+/HER2- advanced breast cancer after aromatase inhibitor (NCT02437318)
Most common side effects
high blood glucose, raised creatinine, diarrhoea, rash, low lymphocytes, raised GGT, nausea, raised ALT, fatigue, low haemoglobin
Notes
FDA approval summary (2019); 572 patients randomised in total. Hyperglycaemia and rash are the main side effects to manage.
Source
FDA approval summary

In the EU summary (EPAR)

SOLAR-1 vs placebo + fulvestrant, 340 with PIK3CA mutation
PFS 11.0 months vs 5.7 months, HR 0.65 (0.50-0.85)

Trial details and side effects
Patients
PIK3CA-mutant cohort, HR+/HER2- advanced breast cancer after aromatase inhibitor (NCT02437318)
Most common side effects
high blood glucose, raised creatinine, diarrhoea, rash, low lymphocytes, raised GGT, nausea, raised ALT, fatigue, low haemoglobin
Notes
EU figures from the EPAR summary; trial details and side effects from the US approval.
Source
EU summary (EPAR)

Biomarkers

BiomarkerActive trialsAll trialsFurthest active phase
PIK3CA activating mutation 12 33 Phase 2/3
ALK fusion 1 1 Phase 2
BRAF V600E 0 1 –
BRCA1/2 mutation 0 1 –
HER2 (ERBB2) activating mutation 0 1 –

Sponsors

Industry sponsors leading active biomarker-selected trials of alpelisib.

  1. Novartis 5
  2. Roche 1
  3. Stemline Therapeutics 1
  4. Criterium 1

Trials

13 of 36 trials shown

  1. Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation.

    Recruiting Phase 2/3 Novartis Started 2023Primary completion 2028-05 NCT05948943

    alpelisib FDA EU

    Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation.

    PIK3CA activating mutationLymphatic Malformations

  2. A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy

    Recruiting Phase 3 Roche Started 2023Primary completion 2026-11 NCT05646862

    inavolisib FDA EUfulvestrant FDA EUalpelisib FDA EUBupropionOmeprazolemidazolam

    …Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Ther…

    PIK3CA activating mutationBreast Cancer

  3. Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant in Participants With HR-positive (HR+), HER2-negative, Advanced Breast Cancer After Treatment With a CDK4/6 Inhibitor and an Aromatase Inhibitor.

    Active, not recruiting Phase 3 Novartis Started 2021Primary completion 2027-01 NCT05038735

    alpelisib FDA EUfulvestrant FDA EU

    The presence of PIK3CA mutation(s) determined in tumor tissue prior to enrollment either by a Novartis designated laborat…

    PIK3CA activating mutationBreast Cancer

  4. Study of Alpelisib (BYL719) in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy in Patients With HER2-positive Advanced Breast Cancer With a PIK3CA Mutation

    Active, not recruiting Phase 3 Novartis Started 2020Primary completion 2027-02 NCT04208178

    alpelisib FDA EUtrastuzumabpertuzumab

    Applies only to Part 2: Participant has a PIK3CA mutation(s) present in tumor prior to enrollment, locally confirmed per test listed in protocol or…

    PIK3CA activating mutationAdvanced HER2+Breast Cancer

  5. Multidisciplinary Treatment of Stage III ALK+ NSCLC With Neoadjuvant Alectinib and Chemotherapy

    Not yet recruiting Phase 2 Wen-zhao ZHONG Started 2026Primary completion 2030-02 NCT07573696

    alpelisib

    …sults as ordered by a healthcare provider from a high-quality and appropriately validated ALK fusion test on tumor tissue performed in a Clinical Laboratory Improvement Amendments Certified …

    ALK fusionNonsmall Cell Lung Cancer Stage III

  6. A Study of Alpelisib and Fulvestrant to Treat Endometrial Cancer

    Active, not recruiting Phase 2 GOG Foundation Started 2024Primary completion 2028-05 NCT05154487

    alpelisib FDA EUfulvestrant FDA EU

    …based on hysterectomy or biopsy specimen and have positive expression of ER and oncogenic PIK3CA mutation per criteria below.

    PIK3CA activating mutationEndometroid Endometrial Cancer

  7. Open-Label Umbrella Study To Evaluate Safety And Efficacy Of Elacestrant In Various Combination In Participants With Metastatic Breast Cancer

    Active, not recruiting Phase 1/2 Stemline Therapeutics Started 2023Primary completion 2026-12 NCT05563220

    elacestrantalpelisib FDA EUeverolimusribociclibpalbociclib FDA EUcapivasertib FDA EUabemaciclib

    Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation by local laboratory assessment.

    PIK3CA activating mutationBreast Cancer, Metastatic Breast Cancer

  8. Clinical Trial of Alpelisb and Tucatinib in Patients With PIK3CA-Mutant HER2+ Metastatic Breast Cancer.

    Active, not recruiting Phase 1/2 Criterium Started 2022Primary completion 2026-03 NCT05230810

    alpelisib FDA EUtucatinibfulvestrant FDA EU

    Documented presence of activating mutation in PIK3CA in the tumor, based on the analysis of solid or liquid biopsy by an assay approved for cl…

    PIK3CA activating mutationHER2-positive Metastatic Breast Cancer

  9. SEQUence of Endocrine Therapy in Advanced Luminal Breast Cancer (SEQUEL-Breast)

    Active, not recruiting Phase 2 Borstkanker Onderzoek Groep Started 2022Primary completion 2026-05 NCT05392608

    alpelisib FDA EUfulvestrant FDA EU

    The presence of an activating PIK3CA mutation

    PIK3CA activating mutationNeoplasm, Breast, Congenital, Familial and Genetic Disorders

  10. Preventing High Blood Sugar in People Being Treated for Metastatic Breast Cancer

    Active, not recruiting Phase 2 Memorial Sloan Kettering Cancer Center Started 2021Primary completion 2027-10 NCT05090358

    alpelisib FDA EUfulvestrant FDA EUCanagliflozin

    Presence of one or more activating PIK3CA mutations in tumor tissue.

    PIK3CA activating mutationBreast Cancer, Breast Cancer Stage IV, Metastatic Breast Cancer

  11. Study Assessing the Efficacy and Safety of Treatment With Alpelisib Plus Fulvestrant Versus Placebo Plus Fulvestrant in Chinese Men and Postmenopausal Women With Advanced Breast Cancer

    Active, not recruiting Phase 2 Novartis Started 2021Primary completion 2027-01 NCT04544189

    alpelisib FDA EUfulvestrant FDA EU

    Participant has identified PIK3CA mutation (as determined by a Novartis designated laboratory)

    PIK3CA activating mutationBreast Neoplasms

  12. Alpelisib (BYL719) in Combination With Continued Endocrine Therapy Following Progression on Endocrine Therapy in Hormone Receptor Positive, HER2 Negative, PIK3CA Mutant Metastatic Breast Cancer

    Active, not recruiting Phase 2 Marina N Sharifi Started 2021Primary completion 2025-10 NCT04762979

    alpelisib FDA EUfulvestrant FDA EUAromatase inhibitor

    PIK3CA mutation identified via local testing from tumor tissue or blood.

    PIK3CA activating mutationHormone Receptor Positive Breast Carcinoma, HER2-negative Breast Cancer, PIK3CA Mutant Metastatic Breast Cancer

  13. Study Assessing the Efficacy and Safety of Treatment With Alpelisib Plus Fulvestrant in Japanese Men and Postmenopausal Women With Advanced Breast Cancer

    Active, not recruiting Phase 2 Novartis Started 2021Primary completion 2027-02 NCT04524000

    alpelisib FDA EUfulvestrant FDA EU

    Participant has identified PIK3CA mutation (as determined by a Novartis designated laboratory)

    PIK3CA activating mutationAdvanced Breast Cancer