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BEZ235

Phase 2

Pancreatic Neuroendocrine Tumors (pNET) | Small molecule | Oncology |Novartis AG|Last Updated: Dec 9, 2020

Success Probability

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Trial Design

UNCONTROLLEDDMC
Total Trials1
Total Enrollment31

FDA Designations

No designations recorded

Clinical trial landscape

BEZ235 · 4 trials · 6 indications

Phase 2 1Phase 1 3
NCT01658436BEZ235 Phase II Trial in Patients With Advanced Pancreatic Neuroendocrine Tumors (pNET) After Failure of mTOR Inhibitor Therapy.Pancreatic Neuroendocrine Tumors (pNET)
COMPLETED31 Analytics
PHASE2COMPLETED
BEZ235 Phase II Trial in Patients With Advanced Pancreatic Neuroendocrine Tumors (pNET) After Failure of mTOR Inhibitor Therapy.
Pancreatic Neuroendocrine Tumors (pNET)Unlock trial analytics

Study Endpoints

Primary Endpoints

Stage 1 - Progression Free Survival (PFS) Rate Analysis at 16 Weeks as Per Local Radiology Review
16 weeks after the first BEZ235 administration.

PFS rate at 16 weeks was defined as a binary variable. Patients were considered as 'progression free' after 16 weeks if they had an overall lesion response of complete response (CR) partial response ('PR) or stable disease (SD)' and "progressed" if they had an overall lesion response of 'Progressive disease (PD) at the scan which occurred on day 105 after start of treatment, or later. Patients whose 16 weeks tumor assessment was unknown, missing or outside the window was not considered as 'progression free' and was considered a "failure" and counted only in the denominator for the estimation of the 16 week progression free rate.

Incidence of dose limiting toxicities (DLTs)
from days 1-35 in BEZ235/abiraterone acetate arm and from days 1-28 in BKM120/abiraterone acetate arm

Dose escalation part: Determine MTD and /or RDE of the combinations abiraterone acetate + BEZ235 and abiraterone acetate + BKM120 by assessing the incidence of DLTs in cycle 1

Prostate specific antigen (PSA) decline ≥ 30%
At week 12 or later after treatment discontinuation

Dose expansion part: Assess anti-tumor activity of the combinations (abiraterone acetate + BEZ235 and abiraterone acetate + BKM120) in castration-resistant prostate cancer patients with abiraterone acetate failure as on treatment PSA progression according to prostate cancer working group criteria 2 (PCWG2) by assessing PSA decline ≥ 30% at Week 12 or later.

To establish Maximum tolerate dose (MTD)
Every week
determine the maximum Tolerated Dose (MTD) of BEZ235 as single agent and in combination with trastuzumab (Dose escalation part)
at end of study
assess the safety & tolerability of BEZ235 SDS as single agent and in combination with trastuzumab administered to patients at the MTD level (Safety expansion part)
at end of study

Secondary Endpoints

Stage 1- Overall Response Rate (ORR)
Baseline, every 8 weeks up to 31 months
Stage 1 - Disease Control Rate
Baseline, every 8 weeks up to 31 months
Number of patients with at least one adverse event
Treatment start until 30 days after the last dose
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
BEZ235 300 mg/400 mg bid (Stage 1)EXPERIMENTALStage 1 consisted of a single arm where patients received BEZ235 300mg or 400mg bid. Initially the study started with a dose of 400mg bid. However, following an amendment after the preliminary safety and tolerability data from the first 3 patients treated at the 400mg dose, the dosage was changed to 300mg bid.
Dose escalation: BEZ235 + Zytiga®EXPERIMENTALBEZ235 oral twice daily: 200 mg, 300 mg, and 400 mg dose levels to be tested in the dose escalation part in combination with abiraterone acetate Zytiga® abiraterone acetate oral once daily: 1000 mg taken with low dose prednisone as per the label
Dose escalation: BKM120 + Zytiga®EXPERIMENTALBKM120 oral once daily: 60 mg, 80 mg and 100 mg dose levels to be tested in the dose escalation part in combination with abiraterone acetate Zytiga® abiraterone acetate oral once daily: 1000 mg taken with low dose prednisone as per the label
Dose expansion: BEZ235 + Zytiga®EXPERIMENTALBEZ235 oral twice daily: 200 mg, 300 mg, and 400 mg dose levels to be tested in the dose escalation part in combination with abiraterone acetate Zytiga® abiraterone acetate oral once daily: 1000 mg taken with low dose prednisone as per the label
Dose Expansion: BKM120 + Zytiga®EXPERIMENTALBKM120 oral once daily: 60 mg, 80 mg and 100 mg dose levels to be tested in the dose escalation part in combination with abiraterone acetate Zytiga® abiraterone acetate oral once daily: 1000 mg taken with low dose prednisone as per the label
BEZ235 Dose Escalation once dailyEXPERIMENTALoral BEZ235 once daily (q.d.)
BEZ Dose escalation twice dailyEXPERIMENTALoral BEZ235 twice daily (b.i.d.)
BEZ235 Alone, Dose EscalationEXPERIMENTAL -
BEZ235 + trastuzumab, Dose EscalationEXPERIMENTAL -
BEZ235 Alone, MTD ExpansionEXPERIMENTAL -
BEZ235 + Trastuzumab, MTD ExpansionEXPERIMENTAL -

Interventions

NameTypeDescription
BEZ235 (Stage 1)DRUGThe investigational study drug used in this trial was BEZ235, which was supplied as 50mg, 200mg, 300mg, and 400mg solid dispersion sachets. Supply as 200mg and 50mg were provided for dose reduction. Patients were instructed to take the contents of one sachet of BEZ235 twice a day in the morning within 30 minutes after a light meal (breakfast).
BEZ235DRUGBEZ235 will be supplied as 50mg, 100mg, 200mg, 300mg and 400mg SDS sachets. At each patient's visit, patient will reecive a prescription of an adequate drug supply for self administration at home.
BKM120DRUGBKM120 will be supplied as 10mg and 50mg hard gelatin capsules. At each patient's visit, patient will reecive a prescription of an adequate drug supply for self administration at home.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites17

Inclusion Criteria: * Unresectable or metastatic, histologically confirmed low or intermediate grade pancreatic neuroendocrine tumor with radiological evidence of disease progression since last treatment * Refractory disease to treatment with mTOR inhibitor * Measurable disease per RECIST Version 1...

Countries:United StatesAustriaBelgiumFranceGermanyItalyNetherlandsSpainUnited KingdomCanadaJapan
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Frequently asked questions about BEZ235

What is BEZ235 used for?

BEZ235 is an investigational small molecule being studied in oncology for multiple tumor types, including pancreatic neuroendocrine tumors (pNET), advanced solid tumors, breast cancer, locally advanced breast cancer (LABC), castration-resistant prostate cancer, and metastatic or locally advanced solid tumors. It is not approved and remains in clinical development.

Who makes BEZ235?

BEZ235 is being developed by Novartis AG, a global pharmaceutical company traded on the New York Stock Exchange under the ticker NVS. The drug is an investigational small molecule in the oncology therapeutic area.

What phase is BEZ235 in?

BEZ235 is in Phase 1 clinical development. All completed trials for the drug are Phase 1 studies. It is investigational and has not received FDA approval, as it remains under clinical investigation for various solid tumor indications.

What clinical trials is BEZ235 in?

BEZ235 has been studied in several completed Phase 1 trials, including NCT00620594 in advanced solid malignancies and breast cancer, NCT01195376 in Japanese patients with advanced solid tumors, NCT01471847 in HER2-positive breast cancer with trastuzumab, and NCT01634061 in castration-resistant prostate cancer with abiraterone acetate.

Is BEZ235 the same as other names?

BEZ235 is the primary name for this investigational drug. No alternative names have been established in the clinical trial data, so it is consistently referred to as BEZ235 across studies.