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AZD9496

Phase 1

Breast Cancer | Small molecule | Oncology |AstraZeneca PLC|Last Updated: Aug 25, 2021

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Trial Design

UNCONTROLLED
Total Trials1
Total Enrollment14

FDA Designations

No designations recorded

Clinical trial landscape

AZD9496 · 3 trials · 3 indications

Phase 1 3
NCT03236974Study to Compare the Effects of AZD9496 vs Fulvestrant in Breast Cancer.Postmenopausal Women With ER+ HER2- Primary Breast Cancer
COMPLETED49 Analytics
NCT02780713A Study to Assess the Pharmacokinetics and Safety of Different Forms and Formulations of AZD9496 in Healthy SubjectsBreast Cancer
COMPLETED14 Analytics
NCT02248090AZD9496 First Time in Patients Ascending Dose StudyER+ HER2- Advanced Breast Cancer
COMPLETED45 Analytics
PHASE1COMPLETED
Study to Compare the Effects of AZD9496 vs Fulvestrant in Breast Cancer.
Postmenopausal Women With ER+ HER2- Primary Breast CancerUnlock trial analytics
PHASE1COMPLETED
A Study to Assess the Pharmacokinetics and Safety of Different Forms and Formulations of AZD9496 in Healthy Subjects
Breast CancerUnlock trial analytics
PHASE1COMPLETED
AZD9496 First Time in Patients Ascending Dose Study
ER+ HER2- Advanced Breast CancerUnlock trial analytics

Study Endpoints

Primary Endpoints

Pharmacodynamics changes to estrogen receptor (ER) expression following treatment with AZD9496 or fulvestrant
Tumour biopsy taken at baseline within 6 weeks of planned start of study treatment; on-treatment tumour biopsy taken following 5-14 day on study treatment

Evaluation of AZD9496 and fulvestrant activity in the tumour by assessment of pharmacodynamics biomarker changes i.e. ER expression

Pharmacokinetics: Maximum Plasma Concentration (Cmax) for AZD9496 and Its Metabolites at Each Treatment Period.
Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period

To evaluate maximum observed plasma concentration (Cmax) for AZD9496 and its metabolites M3 and M5 following administration of different AZD9496 formulations and compare with a reference formulation.

Pharmacokinetics: Area Under the Curve From Time Zero to Time With Last Observation (AUC0-t) for AZD9496 and Its Metabolites at Each Treatment Period
Regular Pharmacokinetic measurement: At Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period

To evaluate the area under the plasma concentration-curve from time zero to time of last quantifiable concentration (AUC (0-t) of AZD9496 and its metabolites M3 and M5 following administration of different AZD9496 formulations and compare with a reference formulation

Pharmacokinetics: Maximum Plasma Concentration (Cmax) for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference
Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period

To evaluate maximum plasma concentration (Cmax) of capsule variants by comparing with reference AZD9496

Pharmacokinetics: Area Under the Curve From Time Zero to Time With Last Observation (AUC0-t) for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference
Regular Pharmacokinetic measurement Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period

To evaluate area under curve from time zero to time with last observation (AUC0-t) of variants by comparing with reference AZD9496

Pharmacokinetics: Area Under the Curve From Time Zero to Infinity for Variant A, B and C of AZD9496 Compared to the AZD9496 Reference
Regular Pharmacokinnetic measurement Pre-dose, 0.5, 1, 1.5, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24, and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period

To evaluate area under the curve from time zero to time infinity (AUC 0-infinity) of variants by comparing with reference AZD9496

Pharmacokinetics: Area Under the Curve From Time Zero to Infinity (AUC 0-infinity) for AZD9496 and Metabolites at Each Treatment Period
Regular pharmacokinetic measurement pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 12, hours post-dose on Day 1, 24 and 36 hours post-dose (Day 2), 48 hours post-dose (Day 3), 72 hours post-dose (Day 4) of each treatment period

To evaluate area under the curve from time zero to infinity (AUC 0-infinity) for AZD9496 and its metabolites

Safety and tolerability
Routine safety assessments, throughout the period that patients receive AZD9496 up to 28 days following discontinuation of last dose of study treatment.

Safety and tolerability in terms of adverse events, serious adverse events (including death) and safety measures: ECG, physical examination, vital signs and laboratory variables. Definition of maximum tolerated dose (MTD) or maximum feasible dose (MFD) by measuring the number of evaluable patients with dose-limiting toxicities.Time frame DLT period 28 days

Secondary Endpoints

Pharmacodynamics changes to progesterone receptor (PgR) expression following treatment with AZD9496 or fulvestrant
Tumour biopsy taken at baseline within 6 weeks of planned start of study treatment; on-treatment tumour biopsy taken following 5-14 day on study treatment
Pharmacodynamics changes to Ki67 protein biomarker expression following treatment with AZD9496 or fulvestrant
Tumour biopsy taken at baseline within 6 weeks of planned start of study treatment; on-treatment tumour biopsy taken following 5-14 day on study treatment
Safety and tolerability of AZD9496
From first dose until 28 days after last dose of AZD9496
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Standard armACTIVE_COMPARATORFulvestrant, 500 mg
AZD9496EXPERIMENTAL250 mg bd taken orally for 5-14 days

Interventions

NameTypeDescription
Standard Arm - FulvestrantDRUG500 mg Fulvestrant administered as two consecutive 5 ml intramuscular injections on Day 1, one in each buttock
AZD9496DRUGAdministered at 250 mg bd orally for 5-14 days commencing on Day 1, and continuing up to the day of biopsy
AZD9496 (Reference)DRUGAZD9496 (Reference)
AZD9496 Variant ADRUGAZD9496 Variant A.
AZD9496 Variant BDRUGAZD9496 Variant B
AZD9496 Variant CDRUGAZD9496 Variant C
AZD9496 Variant DDRUGAZD9496 Variant D
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Eligibility Criteria

Age Range18 Years to 120 Years
SexFEMALE
Healthy VolunteersNo
Study Sites12

Inclusion criteria: 1. Signed and dated informed consent form (ICF) 2. Women \>=18 years 3. Patients with newly diagnosed resectable primary breast cancer scheduled to undergo treatment with curative intent by surgery 4. Histologically confirmed invasive breast cancer involving a palpable tumor of ...

Countries:GermanyUnited KingdomUnited StatesSouth Korea
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Competitive Landscape -Breast Cancer 402 trials

Top 20 of 92 competitors

CompanyTickerTrialsLead PhaseDrugs
AstraZeneca PLCAZN47PHASE3Fulvestrant, Capivasertib
Merck & Co., Inc.MRK12PHASE3Pembrolizumab, Paclitaxel, Doxorubicin, Epirubicin, Cyclophosphamide
Eli Lilly and CompanyLLY27PHASE3Abemaciclib, Standard Adjuvant Endocrine Therapy
BioNTech SE Sponsored ADRBNTX7PHASE3DB-1303/BNT323, T-DM1
Gilead Sciences, Inc.GILD13PHASE3Sacituzumab Govitecan-hziy, Eribulin, Capecitabine Product, Gemcitabine, Vinorelbine
Novartis AG Sponsored ADRNVS30PHASE3Ribociclib
Pfizer Inc.PFE34PHASE3ARV-471, Fulvestrant
BeOne Medicines Ltd. Sponsored ADRONC5PHASE3BGB-43395, Letrozole, Abemaciclib, Palbociclib, Ribociclib
Olema Pharmaceuticals, Inc.OLMA5PHASE3Palazestrant, Fulvestrant, Anastrozole, Letrozole, Exemestane
Jazz Pharmaceuticals Public Limited CompanyJAZZ3PHASE3Zanidatamab, Trastuzumab, Eribulin, Vinorelbine, Gemcitabine
Celcuity Inc.CELC3PHASE3Gedatolisib, Palbociclib, Fulvestrant, Alpelisib
Relay Therapeutics, Inc.RLAY2PHASE3Zovegalisib, Capivasertib, Fulvestrant
GSK plc Sponsored ADRGSK2PHASE3Niraparib
Greenwich LifeSciences, Inc.GLSI1PHASE3GLSI-100
Bristol-Myers Squibb CompanyBMY5PHASE2Iza-bren, Nab-paclitaxel, Paclitaxel, Capecitabine, Carboplatin
BriaCell Therapeutics CorpBCTX2PHASE3SV-BR-1-GM, Cyclophosphamide, Interferon infiltration of the inoculation site, Retifanlimab, Treatment of Physician's Choice
Incyte CorporationINCY4PHASE2Ruxolitinib, Capecitabine, Regorafenib
Natera, Inc.NTRA3PHASE2Discontinuation of the anti-HER2 maintenance therapy
Puma Biotechnology, Inc.PBYI3PHASE2Neratinib, Loperamide, Colesevelam
Atossa Therapeutics, Inc.ATOS1PHASE2endoxifen, goserelin
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Frequently asked questions about AZD9496

What is AZD9496 used for?

AZD9496 is an investigational small molecule being studied for the treatment of breast cancer, specifically in postmenopausal women with ER+ HER2- primary breast cancer and in ER+ HER2- advanced breast cancer. It is being developed by AstraZeneca PLC (AZN) and is currently in Phase 1 clinical development.

What does AZD9496 target?

AZD9496 is an oral small molecule that targets and degrades the estrogen receptor (ER). It is being studied in ER+ HER2- breast cancer, where it aims to block estrogen receptor signaling. The drug is designed to be given orally and is being evaluated in postmenopausal women.

Who makes AZD9496?

AZD9496 is being developed by AstraZeneca PLC, a global biopharmaceutical company. AstraZeneca's stock ticker is AZN. The drug is currently in Phase 1 clinical trials for the treatment of ER+ HER2- breast cancer.

What phase is AZD9496 in?

AZD9496 is in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. All clinical trials for AZD9496 have been completed, and it is not currently in active trials.

What clinical trials is AZD9496 in?

AZD9496 has been studied in three completed Phase 1 clinical trials. NCT02248090 was a first-in-patient ascending dose study in ER+ HER2- advanced breast cancer. NCT02780713 assessed pharmacokinetics and safety in healthy subjects. NCT03236974 compared AZD9496 to fulvestrant in postmenopausal women with ER+ HER2- primary breast cancer.

Is AZD9496 the same as fulvestrant?

No, AZD9496 is not the same as fulvestrant. AZD9496 is an investigational oral small molecule that degrades the estrogen receptor, while fulvestrant is an approved injectable estrogen receptor antagonist. They were compared in a Phase 1 clinical trial (NCT03236974) in postmenopausal women with ER+ HER2- primary breast cancer.