oestrogen receptor degrader · small molecule

fulvestrant

38 active trials across 11 of our biomarkers, targeting ER. 6 active approvals for a biomarker on marked.bio.

Also known as Faslodex.

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.

Therapy	Biomarker	Tumour	United States	European Union
capivasertib with fulvestrant EU (EMA), 2024 locally advanced or metastatic, one or more PIK3CA/AKT1/PTEN alterations, after an endocrine-based regimen EU marketing authorisation 17/06/2024. Source TruqapBroader labelcapivasertib page	PIK3CA activating mutation	breast (ER+/HER2-)	Not approved	Approved 2024
CAPItello-291 vs placebo + fulvestrant, 289 with an alteration PFS 7.3 months vs 3.1 months, HR 0.50 (0.38-0.65) Trial details and side effects Patients HR+/HER2- advanced breast cancer with PIK3CA/AKT1/PTEN alteration (NCT04305496) Most common side effects diarrhoea, skin reactions, high blood glucose, low lymphocytes, low haemoglobin, nausea, fatigue, raised triglycerides, vomiting, stomatitis Notes EU figures from the EPAR summary; trial details and side effects from the US approval. Source EU summary (EPAR)
inavolisib with palbociclib + fulvestrant EU (EMA), 2025 PIK3CA-mutated, locally advanced or metastatic, recurrence on or within 12 months of completing adjuvant endocrine therapy EU marketing authorisation 18/07/2025. Source Itovebiinavolisib page palbociclib page	PIK3CA activating mutation	breast (ER+/HER2-)	Not approved	Approved 2025
INAVO120 vs placebo + palbociclib + fulvestrant, 325 randomised (1:1) PFS 15.0 months vs 7.3 months, HR 0.43 (0.32-0.59)Response 58% vs 25% Trial details and side effects Patients PIK3CA-mutated, endocrine-resistant HR+/HER2- breast cancer (NCT04191499) Most common side effects low neutrophils, low haemoglobin, high fasting glucose, low platelets, stomatitis, diarrhoea, fatigue, nausea, rash, decreased appetite Notes EU figures from the EPAR summary; trial details and side effects from the US approval. Source EU summary (EPAR)
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 Piqrayalpelisib 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)
capivasertib with fulvestrant FDA, 2023 locally advanced or metastatic, one or more PIK3CA/AKT1/PTEN alterations, after endocrine therapy FDA approval 16/11/2023; companion test FoundationOne CDx. The label covers PIK3CA, AKT1 or PTEN alterations. Source TruqapBroader labelcapivasertib page	PIK3CA activating mutation	breast (HR+/HER2-)	Approved 2023	Not approved
CAPItello-291 vs placebo + fulvestrant, 289 with an alteration PFS 7.3 months vs 3.1 months, HR 0.50 (0.38-0.65) Trial details and side effects Patients HR+/HER2- advanced breast cancer with PIK3CA/AKT1/PTEN alteration (NCT04305496) Most common side effects diarrhoea, skin reactions, high blood glucose, low lymphocytes, low haemoglobin, nausea, fatigue, raised triglycerides, vomiting, stomatitis Notes FDA approval summary (2023); figures are for patients with an alteration. Source FDA approval summary
inavolisib with palbociclib + fulvestrant FDA, 2024 endocrine-resistant, PIK3CA-mutated, locally advanced or metastatic, recurrence on or after adjuvant endocrine therapy FDA approval 10/10/2024; companion test FoundationOne Liquid CDx. Source Itovebiinavolisib page palbociclib page	PIK3CA activating mutation	breast (HR+/HER2-)	Approved 2024	Not approved
INAVO120 vs placebo + palbociclib + fulvestrant, 325 randomised (1:1) PFS 15.0 months vs 7.3 months, HR 0.43 (0.32-0.59)Response 58% vs 25%OS HR 0.64 (0.43-0.97), interim Trial details and side effects Patients PIK3CA-mutated, endocrine-resistant HR+/HER2- breast cancer (NCT04191499) Most common side effects low neutrophils, low haemoglobin, high fasting glucose, low platelets, stomatitis, diarrhoea, fatigue, nausea, rash, decreased appetite Notes FDA approval summary (2024); later OS analysis reported a significant benefit (published 2025, not yet in our data). Source FDA approval summary

Biomarkers

Biomarker	Active trials	All trials	Furthest active phase
PIK3CA activating mutation	29	51	Phase 3
BRCA1/2 mutation	4	6	Phase 3
HER2 (ERBB2) activating mutation	2	4	Phase 2
HER2-low / ultralow (IHC 1+ or 2+/ISH-)	2	5	Phase 1
ESR1 mutation	1	5	Phase 3
KRAS G12C	1	2	Phase 1
KRAS G12D	1	1	Phase 1
ALK fusion	0	1	–
EGFR exon 19 deletion / L858R	0	2	–
FGFR2 fusion or rearrangement	0	2	–
FGFR3 alteration (mutation or fusion)	0	2	–

Trials

38 of 75 trials shown

JYP0035 Capsules Plus Fulvestrant in PIK3CA-Mutant HR+/HER2- Advanced Breast Cancer

Not yet recruiting Phase 3 Chengdu JOYO pharma Started 2026Primary completion 2028-11 NCT07784036

fulvestrant FDA EU

JYP0035 Capsules Plus Fulvestrant in PIK3CA-Mutant HR+/HER2- Advanced Breast Cancer

PIK3CA activating mutationBreast Cancer
A Study of Tersolisib (LY4064809/STX-478) With Other Anti-Cancer Treatments in Participants With Advanced Breast Cancer With a Genetic Change (PIK3CA)

Recruiting Phase 3 Eli Lilly Started 2025Primary completion 2029-05 NCT07174336

STX-478ribociclibpalbociclib FDA EUabemaciclibanastrozoleletrozoleExemestanefulvestrant FDA EU

Have evidence of an activating PIK3CA mutation, detected in tumor or blood samples using an appropriate assay.

PIK3CA activating mutationBreast Neoplasms, Neoplasm Metastasis
A Randomised, Open-label, Multicentre Phase III Clinical Study to Evaluate the Efficacy and Safety of JS105 Combined With Dalpiciclib and Fulvestrant Compared With Dalpiciclib and Fulvestrant in Patients With PIK3CA-mutated, HR-positive, HER2-negative Recurrent or Metastatic Breast Cancer.

Recruiting Phase 3 Risen (Suzhou) Pharma Tech Started 2025Primary completion 2029-05 NCT07207070

JS105Dalpiciclibfulvestrant FDA EU

Patients with unresectable PIK3CA-mutated HR-positive HER2-negative recurrent or metastatic breast cancer;

PIK3CA activating mutationBreast Cancer
Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer

Recruiting Phase 3 Relay Therapeutics Started 2025Primary completion 2028-04 NCT06982521

Zovegalisibcapivasertib FDA EUfulvestrant FDA EU

One or more known primary oncogenic PIK3CA mutation(s)

PIK3CA activating mutationPIK3CA Mutation, HER2- Negative Breast Cancer, Hormone Receptor Positive Tumor, Breast Cancer
Capivasertib+Fulvestrant asTreatment for Locally Advanced(Inoperable) or Metastatic HR+/HER2- Breast Cancer in Chinese Patients

Active, not recruiting Phase 3 AstraZeneca Started 2024Primary completion 2026-10 NCT06635447

capivasertib FDA EUfulvestrant FDA EU

Patients with PIK3CA/AKT1/PTEN alterations confirmed by central laboratory NGS testing. (Note: Applicable exclusively to patients en…

PIK3CA activating mutationBreast Cancer
Saruparib (AZD5305) Plus Camizestrant or Plus Endocrine Therapy, Compared With CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant in HR-Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified), BRCA1, BRCA2, or PALB2m Advanced Breast Cancer

Recruiting Phase 3 AstraZeneca Started 2024Primary completion 2029-12 NCT06380751

saruparibcamizestrantabemaciclibribociclibpalbociclibfulvestrantletrozoleanastrozoleExemestane

Documented germline tumour loss of function mutation in BRCA1, BRCA2, or PALB2

BRCA1/2 mutationAdvanced Breast Cancer
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
Evaluation of Lasofoxifene Combined With Abemaciclib Compared With Fulvestrant Combined With Abemaciclib in Locally Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation

Recruiting Phase 3 LeonaBio Started 2023Primary completion 2027-04 NCT05696626

lasofoxifeneabemaciclib FDAfulvestrant

At least 1 or more ESR1 point mutations in the ESR1 ligand binding domain as assessed in cell- free ctDNA obtained from a blood or breast can…

ESR1 mutationMetastatic Breast Cancer
Study to Evaluate Efficacy & Safety of Afuresertib Plus Fulvestrant in Patients With Locally Advanced or Metastatic HR+/HER2- Breast Cancer

Active, not recruiting Phase 3 Laekna Started 2022Primary completion 2026-10 NCT04851613

afuresertibfulvestrant FDA EU

Only patients with PIK3CA/AKT1/PTEN alterations could include.

PIK3CA activating mutationBreast Cancer
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
A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Participants With PIK3CA-Mutant, Hormone Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer

Active, not recruiting Phase 2/3 Roche Started 2020Primary completion 2023-09 NCT04191499

inavolisib FDA EUpalbociclib FDA EUfulvestrant FDA EU

…b + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Participants With PIK3CA-Mutant, Hormone Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer

PIK3CA activating mutationBreast Cancer
Study of AMXT 1501 and DFMO in Combination With Standard Therapies in Advanced Solid Tumors

Recruiting Phase 1/2 Aminex Therapeutics Started 2026Primary completion 2028-02 NCT07287917

AMXT 1501 DicaprateDFMOfulvestrant FDA EUcapivasertib FDA EUpembrolizumab

…cancer patients: locally advanced or metastatic breast cancer with one or more actionable PIK3CA/AKT1/PTEN-alterations following progression on at least 2 endocrine-based regimens in the metastatic setting or…

PIK3CA activating mutationMelanoma (Skin Cancer), HER2-low Hormone Receptor Positive Breast Cancer
A Phase 1/2a Study of K-1728 in Advanced Solid Tumors

Not yet recruiting Phase 1/2 KymaThera Started 2026Primary completion 2028-09 NCT07861932

K-1728fulvestrant FDA EUpalbociclib FDA EU

Documented activating PIK3CA mutation

PIK3CA activating mutationBreast Neoplasms, Solid Tumors, PIK3CA Gene Mutation
Rash & Diarrhea Prophylaxis With Capivasertib

Recruiting Phase 2 Maryam Lustberg Started 2026Primary completion 2027-04 NCT07426822

capivasertib FDA EULoperamidefulvestrant FDA EUCeterizine

Participants with metastatic breast cancer with one or more PIK3CA/AKT1/PTEN-alterations, as confirmed by local or central testing of tumor tissue and/or circulating tumor DNA (c…

PIK3CA activating mutationMetastatic HR+/HER2- Breast Cancer
A Phase ll, Interventional, Single-arm Study Evaluating the Efficacy and Safety of Inavolisib Plus Ribociclib and Fulvestrant in Chinese Patients With PIK3CA-mutant, HR-positive, HER2-negative Locally Advanced or Metastatic Breast Cancer.

Not yet recruiting Phase 2 Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University Started 2026Primary completion 2028-12 NCT07618390

inavolisib FDA EUribociclibfulvestrant FDA EU

…fficacy and Safety of Inavolisib Plus Ribociclib and Fulvestrant in Chinese Patients With PIK3CA-mutant, HR-positive, HER2-negative Locally Advanced or Metastatic Breast Cancer.

PIK3CA activating mutationBreast Cancer
To Study the Effect of Inavolisib in Combination With Fulvestrant in Participants With Breast Cancer

Recruiting Phase 2 Roche Started 2026Primary completion 2028-10 NCT07368998

inavolisib FDA EUfulvestrant FDA EU

Confirmation of biomarker eligibility: presence of \>= 1 study-eligible PIK3CA mutation

PIK3CA activating mutationBreast Cancer
A Phase II Study of Zongertinib Plus Fulvestrant in Participants With HR-positive/HER2-negative Advanced Breast Cancer Harboring HER2 Mutations.

Not yet recruiting Phase 2 MedSIR Started 2026Primary completion 2028-09 NCT07619066

zongertinib FDAfulvestrant

Known activating HER2 mutation.

HER2 (ERBB2) activating mutationAdvanced Breast Cancer, Hormone Receptor Positive / HER2-negative Breast Cancer, HER2 Mutation
Phase 1/2 Study of ETX-636 in Participants With Advanced Solid Tumors

Recruiting Phase 1/2 Ensem Therapeutics Started 2025Primary completion 2027-06 NCT06993844

ETX-636 dose escalationfulvestrant FDA EU

Tumor harboring an activating PIK3CA mutation detected in either tumor tissue or ctDNA.

PIK3CA activating mutationAdvanced Solid Tumors, Advanced Breast Cancer
SNV4818 in Participants With Advanced Solid Tumors

Recruiting Phase 1/2 Pikavation Therapeutics Started 2025Primary completion 2027-04 NCT06736704

SNV4818fulvestrant FDA EUpalbociclib FDA EU

Advanced or metastatic solid tumor with an activating PIK3CA mutation.

PIK3CA activating mutationAdvanced Solid Tumors
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
I/II Phase Study Evaluating M1774 in Combination With Fulvestrant in HR+ and HER2- Advanced Breast Cancers

Not yet recruiting Phase 1/2 Institut Paoli-Calmettes Started 2024Primary completion 2027-04 NCT05986071

M1774fulvestrant

Germline or somatic BRCA1, BRCA2 or PALB2 mutations and prior exposure and resistance to PARP inhibitors (cohort 1…

BRCA1/2 mutationStatus may be outdated, last updated 2024-03-29Breast Cancer
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
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
Evaluating the Efficacy and Safety of Fulvestrant Plus DNA Damage Repair Inhibitors After a CDK4/6 Inhibitor

Recruiting Phase 2 Seoul National University Hospital Started 2022Primary completion 2025-12 NCT05536128

olaparib FDA EUfulvestrant

13. \<For cohort A\> Patients with known germline or somatic mutations of BRCA1 or BRCA2

BRCA1/2 mutationAdvanced Breast Cancer
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
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
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
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
Basket Study of Tucatinib and Trastuzumab in Solid Tumors With HER2 Alterations

Active, not recruiting Phase 2 Pfizer Started 2021Primary completion 2023-11 NCT04579380

tucatinibtrastuzumabfulvestrant

Known activating HER2 mutations detected in fresh or archival tumor tissue or blood

HER2 (ERBB2) activating mutationUterine Neoplasms, Uterine Cervical Neoplasms, Biliary Tract Neoplasms, Urologic Neoplasms
Durvalumab, With Olaparib and Fulvestrant in Advanced ER+, HER2- Breast Cancer Patients.

Active, not recruiting Phase 2 UNICANCER Started 2019Primary completion 2023-11 NCT04053322

durvalumabolaparib FDA EUfulvestrant

Documented personal germline alteration in BRCA1 or BRCA2 that is predicted to be deleterious.

BRCA1/2 mutationER-positive and HER2-negative Metastatic or Locally Advanced Breast Cancer, a Germline or Somatic BRCA Mutation, or a Deleterious Alteration of Other Genes Involved in Homologous Recombination Repair (HRR) or in MSI Status
A Study to Learn About the Study Medicine Called PF-08165784 in People With PIK3CA-Mutated Advanced or Metastatic Solid Tumors

Not yet recruiting Phase 1 Pfizer Started 2026Primary completion 2030-03 NCT07897721

PF-08165784fulvestrant FDA EUAtirmociclibcetuximabletrozole

Phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) mutation

PIK3CA activating mutationAdvanced Breast Cancer, Advanced or Metastatic Breast Cancer, Metastatic Breast Cancer (HR+/ HER2-), Metastatic Colorectal Adenocarcinoma
Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors

Recruiting Phase 1 BridgeBio Oncology Therapeutics Started 2024Primary completion 2028-11 NCT06625775

BBO-10203trastuzumabfulvestrantribociclibFOLFOXbevacizumab

…-positive advanced breast cancer (aBC), HR-positive/HER2-negative advanced breast cancer, KRAS mutant advanced colorectal cancer (aCRC), or KRAS mutant advanced non-small cell lung cancer (aN…

KRAS G12CKRAS G12DPIK3CA activating mutationSolid Tumor, Adult, Metastatic Breast Cancer, Advanced Breast Cancer, HER2 Mutation-Related Tumors
First-in-Human Study of OKI-219 in Advanced Solid Tumors and Advanced Breast Cancer

Active, not recruiting Phase 1 OnKure Started 2024Primary completion 2026-12 NCT06239467

OKI-219fulvestranttrastuzumabtucatinibAtirmociclibribociclib

Participants with HER2-low breast cancer must have received prior trastuzumab deruxtecan.

HER2-low / ultralow (IHC 1+ or 2+/ISH-)Advanced Cancer, Breast Cancer, Advanced Solid Tumors, PI3K Gene Mutation
A Study to Evaluate the Safety and Tolerability of TOS-358 in Women With HR+ HER2- Breast Cancer

Recruiting Phase 1 Totus Medicines Started 2023Primary completion 2027-12 NCT05683418

TOS-358fulvestrant FDA EUpalbociclib FDA EUribociclib

Known PIK3CA mutations or amplifications as determined at a CAP/CLIA-certified or equivalently accredited diagno…

PIK3CA activating mutationHR+/HER2-negative Breast Cancer
A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors

Active, not recruiting Phase 1 Eli Lilly Started 2022Primary completion 2025-04 NCT05307705

LOXO-783fulvestrant FDA EUimlunestrantabemaciclibanastrozoleletrozolepaclitaxel

… H1047R mutation (or other Sponsor and safety review committee (SRC)-approved, activating PIK3CA mutations other than H1047R mutation)

PIK3CA activating mutationBreast Cancer
First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, as a Single Agent in Patients With Advanced Solid Tumors and in Combination With Endocrine Therapy +/- a CDK4/6 or CDK4 Inhibitor in Patients With Advanced Solid Tumors or Advanced Breast Cancer

Recruiting Phase 1 Relay Therapeutics Started 2021Primary completion 2027-04 NCT05216432

RLY-2608fulvestrant FDA EUpalbociclib FDA EUribociclibPF-07220060 100mgPF-07220060 300 mg

One or more documented primary oncogenic PIK3CA mutation(s) in blood and/or tumor per local assessment

PIK3CA activating mutationPIK3CA Mutation, Solid Tumor, Adult, HER2-negative Breast Cancer, Breast Cancer
A Phase 1b Study of T-DXd Combinations in HER2-low Advanced or Metastatic Breast Cancer

Active, not recruiting Phase 1 AstraZeneca Started 2020Primary completion 2023-08 NCT04556773

trastuzumab deruxtecan FDA EUdurvalumabpaclitaxelcapivasertibanastrozolefulvestrantcapecitabine

Has a history of HER2-low expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) with a validated assay

HER2-low / ultralow (IHC 1+ or 2+/ISH-)Metastatic Breast Cancer
To Evaluate the Safety, Tolerability, and Pharmacokinetics of Inavolisib Single Agent in Participants With Solid Tumors and in Combination With Endocrine and Targeted Therapies in Participants With Breast Cancer

Active, not recruiting Phase 1 Roche Started 2016Primary completion 2026-12 NCT03006172

inavolisib FDA EUfulvestrant FDA EUletrozolepalbociclib FDA EUmetformintrastuzumabpertuzumab

Locally advanced, recurrent, or metastatic, PIK3CA mutant, incurable solid tumor malignancy, including breast cancer

PIK3CA activating mutationBreast Cancer, Solid Tumor
Study to Assess the Safety of Alpelisib Plus Fulvestrant, in Men and Post-menopausal Women With HR-positive, HER2-negative, Advanced Breast Cancer (aBC) With PIK3CA Mutation, Whose Disease Progressed on or After Endocrine Treatment

Completed Phase 4 Novartis Started 2022 NCT05631795

alpelisib FDA EUfulvestrant FDA EU

Participants with confirmed PIK3CA mutant advanced or metastatic breast cancer

PIK3CA activating mutationAdvanced Breast Cancer
The Neoadjuvant Combined Hormone Therapy in Premenopausal Women With Locally Advanced ER+/HER2- Breast Cancer

Unknown status Phase 2/3 Saint Petersburg State Budgetary Healthcare Institution, City Clinical Oncology Dispensary Started 2021 NCT04753177

fulvestrant FDA EUdoxorubicincyclophosphamidepaclitaxel

Providing histological materials to determine the status of mutations in the PIK3CA gene

PIK3CA activating mutationThe Neoadjuvant Therapy
Trastuzumab + Alpelisib +/- Fulvestrant vs Trastuzumab + CT in PIK3CA-mutated HER2+ Advanced BC (ALPHABET)

Terminated Phase 3 Spanish Breast Cancer Research Group Started 2021 NCT05063786

trastuzumabalpelisib FDA EUfulvestrant FDA EUvinorelbinecapecitabineeribulin

Trastuzumab + Alpelisib +/- Fulvestrant vs Trastuzumab + CT in PIK3CA-mutated HER2+ Advanced BC (ALPHABET)

PIK3CA activating mutationHER2 (ERBB2) activating mutationAdvanced Breast Cancer
Study of the Molecular Features of Postmenopausal Women With HR+ HER2-negative aBC on First-line Treatment With Ribociclib and Letrozole and, in Patients With a PIK3CA Mutation, on Second-line Treatment With Alpelisib Plus Fulvestrant

Terminated Phase 3 Novartis Started 2018 NCT03439046

ribociclibletrozolealpelisib FDA EUfulvestrant FDA EU

Patient has PIK3CA mutation as determined in tumor tissue and/or plasma by a Novartis designated laboratory.

PIK3CA activating mutationBreast Cancer
A Study of Taselisib + Fulvestrant Versus Placebo + Fulvestrant in Participants With Advanced or Metastatic Breast Cancer Who Have Disease Recurrence or Progression During or After Aromatase Inhibitor Therapy

Terminated Phase 3 Roche Started 2015 NCT02340221

taselisibfulvestrant FDA EU

A valid cobas PIK3CA mutation result by central testing is required

PIK3CA activating mutationBreast Cancer
Detection of Tumor DNA in the Blood of Patients Receiving Standard Therapy for Hormone Receptor-positive (HR+) Non-HER2 Expressing (HER2-) Metastatic Breast Cancer as a Tool to Select Those Who May Benefit From the Next Course of Fulvestrant in Combination With Alpelisib or Ribociclib

Terminated Phase 2 UNICANCER Started 2023 NCT05625087

alpelisib FDA EUfulvestrant FDA EUribociclib

…lvestrant to Ribociclib Combined With Fulvestrant, in Patients With Persistent Targetable PIK3CA Mutations

PIK3CA activating mutationBreast Cancer Stage IV
A Study to Prevent Rash in People Starting Alpelisib for the Treatment of Breast Cancer

Terminated Phase 2 Memorial Sloan Kettering Cancer Center Started 2023 NCT05966584

Benralizumabfulvestrant FDA EUalpelisib FDA EU

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

PIK3CA activating mutationBreast Cancer
A Phase Ⅰb/Ⅱ Clinical Study of SHR-A1811 Combined With Other Therapies in Patients With HER2 Low Advanced or Metastatic Breast Cancer.

Unknown status Phase 1/2 Jiangsu Hengrui Started 2023 NCT05792410

trastuzumab rezetecanfulvestrantbevacizumab

…18-75 years old (including both ends), female patients who have pathologically documented HER2 low breast cancer

HER2-low / ultralow (IHC 1+ or 2+/ISH-)HER2 Low Advanced or Metastatic Breast Cancer
Dalpiciclib Plus Fulvestrant With Pyrotinib in Hormone Receptor-positive, HER2-low Advanced Breast Cancer That Progressed on Previous CDK4/6i Plus AI Therapy

Unknown status Phase 2 Tianjin Medical University Cancer Institute and Hospital Started 2023 NCT05806671

Dalpiciclibpyrotinibfulvestrant

HER2-low breast cancer defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested). (as per the ASCO-CAP g…

HER2-low / ultralow (IHC 1+ or 2+/ISH-)Breast Cancer
Study of Safety and Efficacy of Dapagliflozin + Metformin XR Versus Metformin XR in Participants With HR+, HER2-, Advanced Breast Cancer While on Treatment With Alpelisib and Fulvestrant

Terminated Phase 2 Novartis Started 2022 NCT04899349

alpelisib FDA EUfulvestrant FDA EUmetforminDapagliflozin

Participant had a PIK3CA mutation(s) present in the tumor prior to enrollment.

PIK3CA activating mutationBreast Cancer
Pilot Decentralized Clinical Trial in Men and Pre and Post-menopausal Women With Breast Cancer and a Specific Mutation (PIK3CA) Treated With Alpelisib in Combination With Fulvestrant

Terminated Phase 2 Novartis Started 2022 NCT04862143

alpelisib FDA EUfulvestrant FDA EUGoserelin

…edicine Platform in Patients With HR-positive/HER2-negative Advanced Breast Cancer With a PIK3CA Mutation Treated With Alpelisib - Fulvestrant TELEPIK Trial

PIK3CA activating mutationAdvanced Breast Cancer
Fulvestrant Plus Anlotinib in HR(+)/HER2(-) Metastatic Breast Cancer With FGFR Mutation

Unknown status Phase 2 Sun Yat-sen University Started 2021 NCT04936295

fulvestrantanlotinib

There are FGFR mutations, which meets any of the following: ①Immunohistochemical method: any subtype of FGFR1/2/3/…

FGFR3 alteration (mutation or fusion)FGFR2 fusion or rearrangementBreast Cancer
Study to Evaluate the Effect of Metformin in the Prevention of HG in HR[+]/HER2[-] PIK3CA-mut Advanced BC Patients

Completed Phase 2 MedSIR Started 2020 NCT04300790

alpelisib FDA EUmetforminfulvestrant FDA EUletrozoleExemestaneVildagliptinTamoxifen

Presence of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-mutated (PIK3CAMut) determined on the most recent tumor tissue specimen (frozen or formalin-fixed…

PIK3CA activating mutationBreast Cancer
A Study of TQ-B3525 Tablets Combined With Fulvestrant Injection in Subjects With HR-positive, HER2-negative and PIK3CA Mutation Advanced Breast Cancer

Unknown status Phase 1/2 Chia Tai Tianqing (Sino Biopharm) Started 2020 NCT04355520

TQ-B3525fulvestrant FDA EU

…issue obtained within 2 years (surgery or biopsy) for genetic mutation detection and with PIK3CA mutation positive.

PIK3CA activating mutationHR-positive, HER2-negative and PIK3CA Mutation Advanced Breast Cancer
Study of eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies

Unknown status Phase 1/2 Effector Therapeutics Started 2019 NCT04092673

eFT226sotorasib FDA EUfulvestrantabemaciclibtrastuzumab

Tumor has a known G12C KRAS-activating mutation.

KRAS G12CSolid Tumor, Adult
A Study of a New Drug Combination, Copanlisib and Fulvestrant, in Advanced Breast Cancer

Withdrawn Phase 1/2 National Cancer Institute (NCI) Started 2019 NCT03803761

copanlisibfulvestrant FDA EU

Patients must have had tumor sequencing for evaluation of actionable PIK3CA or PTEN mutations performed in a Clinical Laboratory Improvement Act (CLIA) certified, College of American …

PIK3CA activating mutationAnatomic Stage IV Breast Cancer AJCC v8, Metastatic Breast Carcinoma, Metastatic Malignant Neoplasm in the Brain, Prognostic Stage IV Breast Cancer AJCC v8
Evaluation of Lasofoxifene Versus Fulvestrant in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation

Completed Phase 2 Sermonix Pharmaceuticals Started 2019 NCT03781063

lasofoxifenefulvestrant

At least one or more of the following point ESR1 mutations as assessed in cell-free circulating tumor DNA (ctDNA) obtained from a blood (plasma) or …

ESR1 mutationLocally Advanced or Metastatic Breast Cancer
Aromatase Inhibitor Therapy With or Without Fulvestrant for the Treatment of HR Positive Metastatic Breast Cancer With an ERS1 Activating Mutation, the INTERACT Study

Terminated Phase 2 M.D. Anderson Cancer Center Started 2019 NCT04256941

abemaciclib FDAanastrozolefulvestrantletrozolepalbociclibribociclib

Activating ESR1 mutation (e.g.

ESR1 mutationAnatomic Stage IV Breast Cancer AJCC v8, Metastatic Breast Carcinoma, Prognostic Stage IV Breast Cancer AJCC v8
SAFIR-PI3K A Phase II Randomized Maintenance Trial Comparing Alpelisib and Fulvestrant Versus Chemotherapy in PIK3CA Mutated Advanced Breast Cancer

Terminated Phase 2 UNICANCER Started 2018 NCT03386162

alpelisib FDA EUfulvestrant FDA EUChemotherapy

Presence of PIK3CA mutation on exon 9 or 20, determined on metastatic tissue specimen (frozen or FFPE) or plasma (ctD…

PIK3CA activating mutationBreast Cancer, PI3K, Alpelisib
MCLA-128 With Trastuzumab/Chemotherapy in HER2+ and With Endocrine Therapy in ER+ and Low HER2 Breast Cancer.

Completed Phase 2 Merus Started 2018 NCT03321981

zenocutuzumabtrastuzumabvinorelbinefulvestrantletrozole

…apy in HER2-positive MBC and MCLA-128/Endocrine Therapy in Estrogen Receptor Positive and Low HER2 Expression MBC

HER2-low / ultralow (IHC 1+ or 2+/ISH-)Breast Cancer Metastatic
Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole, Based on Prior Endocrine Therapy, in Patients With PIK3CA Mutant, HR+, HER2- Advanced Breast Cancer Who Have Progressed on or After Prior Treatments

Completed Phase 2 Novartis Started 2017 NCT03056755

alpelisib FDA EUfulvestrant FDA EUletrozoleGoserelinLeuprolide

…th gene encoding the p110alpha catalytic subunit of PI3K (phosphatidylinositol-3-kinase) (PIK3CA) mutation.

PIK3CA activating mutationBreast Cancer
The Efficacy of Fulvestrant in ESR1(Estrogen Receptor 1) Mutated Metastatic Breast Cancer

Unknown status Phase 2 Fudan University Started 2017 NCT03202862

fulvestrant

The blood sample is clarified to be ESR1 mutated, The mutation should be: Y537C, Y537N, Y537S, S463P and D538G.

ESR1 mutationBreast Neoplasms
Lung Cancer in Women Treated With Anti-oestrogens anD Inhibitors of EGFR

Completed Phase 2 Intergroupe Francophone de Cancerologie Thoracique Started 2012 NCT01556191

gefitinib FDA EUfulvestranterlotinib FDA EU

The presence of analysable tissue for the research of EGFR activating mutation.

EGFR exon 19 deletion / L858RStage IV Lung Cancer
Neratinib +/- Fulvestrant in Metastatic HER2 Non-amplified But HER2 Mutant Breast Cancer

Completed Phase 2 Washington University School of Medicine Started 2012 NCT01670877

neratinibfulvestranttrastuzumab

for Registration (for patients with HER2 mutation identified at an outside CLIA certified location):

HER2 (ERBB2) activating mutationBreast Neoplasms
First-in-Human Study of RLY-5836 in Advanced Breast Cancer and Other Solid Tumors

Completed Phase 1 Relay Therapeutics Started 2023 NCT05759949

RLY-5836fulvestrant FDA EUpalbociclib FDA EUribociclibabemaciclib

One or more documented primary oncogenic PIK3CA mutation(s) in blood and/or tumor per local assessment

PIK3CA activating mutationPIK3CA Mutation, Solid Tumor, Adult, HER2-negative Breast Cancer, Breast Cancer
A Phase Ib Study of HS-10352 Plus Fulvestrant in Patients With Advanced Breast Cancer

Unknown status Phase 1 Hansoh Pharma Started 2022 NCT05504213

fulvestrant FDA EU

At dose expansion stage, participants should be identified as PIK3CA-mutation positive before enrollment.

PIK3CA activating mutationBreast Cancer
Study of CYH33 in Combination With Endocrine Therapy With or Without Palbociclib in Patients With HR+, HER2- Advanced Breast Cancer

Unknown status Phase 1 Haihe Biopharma Started 2021 NCT04856371

CYH33fulvestrant FDA EUletrozolepalbociclib FDA EU

For Stage 2 dose expansion phase, patients with PIK3CA mutations are required.

PIK3CA activating mutationAdvanced Breast Cancer
HOPE: Olaparib, Palbociclib and Fulvestrant in Patients With BRCA Mutation-associated, HR+, HER2-metastatic Breast Cancer

Completed Phase 1 Abramson Cancer Center at Penn Medicine Started 2020 NCT03685331

palbociclibolaparib FDA EUfulvestrant

Germline or somatic deleterious or suspected deleterious mutation in BRCA1 or BRCA2

BRCA1/2 mutationMetastatic Breast Cancer, Locally Advanced Breast Cancer, Advanced Breast Cancer, BRCA2 Mutation
Rogaratinib, Palbociclib y Fulvestrant in Patients With Breast Cancer.

Completed Phase 1 Fundacion CRIS de Investigación para Vencer el Cáncer Started 2020 NCT04483505

rogaratinibpalbociclibfulvestrant

Rogaratinib, Palbociclib and Fulvestrant in Advanced Hormone Receptor Positive, FGFR1/2/3-positive Breast Cancer: Phase I Clinical Trial Plus an Expansion Cohort

FGFR3 alteration (mutation or fusion)FGFR2 fusion or rearrangementBreast Cancer Metastatic, Hormone Receptor Positive Malignant Neoplasm of Breast
MEN1611 With Trastuzumab (+/- Fulvestrant) in Metastatic Breast Cancer

Completed Phase 1 Menarini Group Started 2018 NCT03767335

MEN1611trastuzumabfulvestrant FDA EU

Advanced or metastatic breast cancer harbouring PIK3CA mutation on tissue sample

PIK3CA activating mutationAdvanced or Metastatic Breast Cancer
This Study in Patients With Different Types of Cancer (Solid Tumours) Aims to Find a Safe Dose of Xentuzumab in Combination With Abemaciclib With or Without Hormonal Therapies. The Study Also Tests How Effective These Medicines Are in Patients With Lung and Breast Cancer

Completed Phase 1 Boehringer Ingelheim Started 2017 NCT03099174

Xentuzumababemaciclibletrozoleanastrozolefulvestrant

…anaplastic lymphoma kinase (ALK) inhibitors is mandatory in participants whose tumour has EGFR-activating mutations or ALK translocations.

EGFR exon 19 deletion / L858RALK fusionNeoplasms, Breast Neoplasms
Vevorisertib (ARQ 751) as a Single Agent or in Combination With Other Anti-Cancer Agents, in Solid Tumors With PIK3CA / AKT / PTEN Mutations (MK-4440-001)

Terminated Phase 1 ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) Started 2016 NCT02761694

Vevorisertibfulvestrant FDA EUpaclitaxel

Documented AKT genetic alterations or known actionable PIK3CA/PTEN mutations by genetic testing

PIK3CA activating mutationCancer, Solid Tumors
Phase I, Dose Study to Look at the Safety and Pharmacokinetics of AZD8835 in Patients With Advanced Solid Tumours

Completed Phase 1 AstraZeneca Started 2014 NCT02260661

AZD8835fulvestrant FDA EU

…tive, HER2 negative breast cancer and disease progression or any other solid tumor with a PIK3CA gene mutation.

PIK3CA activating mutationAdvanced Solid Malignancies, Breast Cancer - ER+, HER2 -, Breast Cancer - ER+, HER2-, PIK3CA Gene Mutation
A Dose Escalation Study Evaluating the Safety and Tolerability of GDC-0032 in Participants With Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma (NHL) and in Combination With Endocrine Therapy in Locally Advanced or Metastatic Hormone Receptor-Positive Breast Cancer

Terminated Phase 1 Roche Started 2011 NCT01296555

fulvestrant FDA EUtaselisibletrozolemidazolam

Phase I (Cohort X): Participants with PIK3CA-mutant tumors and measurable disease per RECIST v1.1

PIK3CA activating mutationSolid Cancers, Non-Hodgkin's Lymphoma
A Study of BYL719 in Adult Patients With Advanced Solid Malignancies, Whose Tumors Have an Alteration of the PIK3CA Gene

Completed Phase 1 Novartis Started 2010 NCT01219699

alpelisib FDA EUfulvestrant FDA EU

… Study of BYL719 in Adult Patients With Advanced Solid Malignancies, Whose Tumors Have an Alteration of the PIK3CA Gene

PIK3CA activating mutationAdvanced Solid Tumors With an Alteration of the PIK3CA Gene, Estrogen Receptor Positive Breast Cancer
SMMART Adaptive Clinical Treatment (ACT) Trial

Withdrawn Early Phase 1 OHSU Knight Cancer Institute Started 2023 NCT05238831

alectinibalpelisibanastrozoleatezolizumabbevacizumab FDA EUcapecitabinecarboplatincobimetinibentrectiniberibulinfulvestrantpertuzumab

… least one prior line of therapy with a PARP inhibitor for triple negative disease with a BRCA1/2 mutation.

BRCA1/2 mutationAdvanced Breast Carcinoma, Advanced Malignant Solid Neoplasm, Advanced Ovarian Carcinoma, Advanced Pancreatic Carcinoma
Treatment of Metastatic Breast Cancer With Fulvestrant Plus Palbociclib or Tamoxifen Plus Palbociclib

Completed Early Phase 1 Shannon Puhalla Started 2018 NCT02913430

fulvestrantTamoxifenpalbociclib

…Fulvestrant Plus Palbociclib or Tamoxifen Plus Palbociclib: A Randomized Pilot Trial With ESR1 Mutation Tested in Circulating Tumor DNA.

ESR1 mutationMetastatic Breast Cancer

Approvals and pivotal results

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