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ZD6474

Phase 3

Non-Small-Cell Lung Carcinoma | Small molecule | Oncology |Sanofi|Last Updated: Sep 24, 2025

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials1
Total Enrollment1,140

FDA Designations

No designations recorded

Clinical trial landscape

ZD6474 · 16 trials · 18 indications

Phase 3 2Phase 2 9Phase 1 5
NCT00410761An Efficacy Study Comparing ZD6474 to Placebo in Medullary Thyroid CancerThyroid Cancer
COMPLETED331 Analytics
NCT00404924ZD6474 (ZACTIMA™) Phase III Study in EGFR FailuresNon-Small-Cell Lung Carcinoma
COMPLETED1,140 Analytics
PHASE3COMPLETED
An Efficacy Study Comparing ZD6474 to Placebo in Medullary Thyroid Cancer
Thyroid CancerUnlock trial analytics
PHASE3COMPLETED
ZD6474 (ZACTIMA™) Phase III Study in EGFR Failures
Non-Small-Cell Lung CarcinomaUnlock trial analytics

Study Endpoints

Primary Endpoints

Progression-Free Survival(PFS)
RECIST tumour assessments were performed at screening (within 3 weeks before date of randomisation), then once every 12 weeks up to and including discontinuation of blinded study treatment, unless patients had withdrawn consent.

Median time to progression (months) from randomisation until objective disease progression (determined by RECIST assessments) or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment. Values here are estimated (from a Weibull model) as the medians were not met.

Overall Survival (OS)
Time to death in months

Overall Survival (OS) is defined as the time from date of randomization until death. Any blinded/unknown patient which have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie, their status must be known at the censored date and should not be lost to follow up or unknown).

Prostate Specific Antigen (PSA) Progression Free Rate at 4 Months
4 months

To assess the effect of vandetanib on biological progression free rate based on PSA level (assessable set). PSA progression free rate defined as the number of participants with : * After decline from baseline: a 25% increase above the nadir * No decline from baseline: a 25% increase above the baseline (min. increase of 2 ng/mL)

Objective Response Rate (ORR)
RECIST assessed at screening (up to 3 weeks prior to first dose), then every 12 weeks (± 2 weeks), from date of first dose to objective progression, up to and including discontinuation of study treatment.

The ORR is the number of patients that are responders ie those patients with a confirmed best objective response of complete response (CR) or partial response (PR) as defined by RECIST criteria. The categories for best objective response are CR, PR, stable disease (SD)\>= 12 weeks, progressive disease (PD) or NE.

To assess the objective response rates (by RECIST) to ZD6474 100, 200 and 300 mg/day respectively
Every 4 weeks for the first 24 weeks of treatment and then every 8 weeks until PD is determined or withdrawal due to any reasons other than PD. If PR or CR is observed, tumour assessment will be repeated 4 weeks after for confirmation of the response
Objective Response Rate
Pre-dose and every 12 weeks up to RECIST progression as defined according to RECIST 1.0.

The ORR is the number of patients that are responders ie those patients with a confirmed best objective response of complete response (CR) or partial response (PR) defined according to RECIST 1.0.

Primary Outcomes:
Part A
i. Time to progression
ii. Incidence, CTC grade and type of Aes, clinically significant laboratory abnormalities or changes in vital signs, and ECG changes
Part B
Outcome Progression free survival
To determine the maximum tolerated dose of vandetanib given in combination with radiation or radiation and chemotherapy in patients with late stage head and neck cancer
assessed at each visit
Assess by dynamic contrast-enhanced magnetic resonance imaging the effect of once daily dosing with ZD6474 on tumour perfusion and vascular permeability in patients with advanced colorectal cancer and liver metastases.
Up to 57 days.
Safety and tolerability of ZD6474 in combination with 5-Fluorouracil, Leucovorin and Oxaliplatin
Assessed at each visit
Establish the safety & efficacy of ZD6474 w/5-fluorouracil,leucovorin & oxaliplatin to patients with advanced colorectal adenocarcinoma, by assessment of AEs, vital signs, clinical chemistry, hematology, urinalysis, ECG and physical examinations
assessed at each visit
To establish the safety & tolerability of ZD6474 when administered in combination w/Pemetrexed (Alimta) to patients w/locally advanced or metastatic NSCLC after failure of prior chemo, by assessment of AEs, vital signs, lab, ECG and physical exam.
assessed at each visit

Secondary Endpoints

Objective Response Rate (ORR)
RECIST assessments performed at screening (within 3 weeks before randomisation), then every 12 weeks. For patients with objective response of CR or PR, an additional confirmatory scan was performed ≥4 weeks following the date of first response.
Disease Control Rate (DCR)
RECIST tumour assessments were performed at screening (within 3 weeks before date of randomisation), then once every 12 weeks up to and including discontinuation of blinded study treatment, unless patients had withdrawn consent
Duration of Response (DoR)
RECIST tumour assessments were performed at screening (within 3 weeks before date of randomisation), then once every 12 weeks up to and including discontinuation of blinded study treatment, unless patients had withdrawn consent
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
1NO_INTERVENTIONPlacebo vandetanib
2EXPERIMENTALVandetanib
ZD6474 100mgEXPERIMENTALDaily dose
ZD6474 200mgEXPERIMENTALdaily dose
ZD6474 300mgEXPERIMENTALdaily dose
Caprelsa (vandetanib) 300 mgEXPERIMENTALDaily oral dose of Caprelsa (vandetanib) 300mg
ZD6474 (vandetanib) 100mgEXPERIMENTAL -
ZD6474 (vandetanib) 300mgEXPERIMENTAL -

Interventions

NameTypeDescription
ZD6474 (Vandetanib)DRUGonce daily oral tablet
Best Supportive CareOTHERstandard of care
BicalutamideDRUG150mg orally, once daily
PlaceboDRUGorally, once daily
ZD6474 (vandetanib) 100mgDRUGonce daily oral dose
ZD6474 (vandetanib) 200mgDRUGonce daily oral dose
ZD6474 (vandetanib) 300mgDRUGonce daily oral dose
ZD6474DRUG -
PaclitaxelDRUG -
CarboplatinDRUG -
ZD1839DRUG -
VEGF-receptor tyrosine kinase (KDR)DRUG -
DocetaxelDRUG -
CisplatinDRUGintravenous infusion
RadiationRADIATIONradiation of head and neck
ZD6474 (Zactima) 100mgDRUG -
Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MR)PROCEDURE -
Biomarker DrawsPROCEDURE -
ZD6474 (Zactima) 300mgDRUG -
5-FluorouracilDRUGintravenous infusion
LeucovorinDRUGintravenous infusion
OxaliplatinDRUGintravenous infusion
IrinotecanDRUGintravenous infusion
pemetrexedDRUGintravenous infusion
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites127

Inclusion Criteria: * Confirmed diagnosis of unresectable, locally advanced or metastatic hereditary or sporadic Medullary Thyroid Cancer. * Presence of measurable tumor * Able to swallow medication Exclusion Criteria: * Major surgery within 4 weeks before randomization * Last dose of prior chemo...

Countries:United StatesAustraliaAustriaBelgiumBrazilCanadaCzechiaDenmarkFranceGermanyHungaryIndiaItalyMexicoNetherlandsPolandPortugalRomaniaRussiaSerbiaSouth KoreaSpainSwedenSwitzerlandArgentinaChinaHong KongIsraelPeruPhilippinesSingaporeTaiwanThailandUnited KingdomJapanFinlandSouth Africa
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Frequently asked questions about ZD6474

What is ZD6474 used for?

ZD6474 is an investigational small molecule being studied for the treatment of several cancers, including non-small cell lung cancer, prostate cancer, and advanced colorectal carcinoma. It has been evaluated in clinical trials for these oncology indications, though it remains in clinical development and is not approved.

What does ZD6474 target?

ZD6474 is a small molecule that targets vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) pathways. By inhibiting these receptors, it aims to block tumor angiogenesis and cancer cell growth, which is relevant to its study in solid tumors like non-small cell lung cancer.

Who makes ZD6474?

ZD6474 is being developed by Sanofi, a global pharmaceutical company listed on the stock exchange under the ticker SNY. Sanofi has sponsored clinical trials of ZD6474 in oncology indications, including non-small cell lung cancer and prostate cancer.

What phase is ZD6474 in?

ZD6474 is in Phase 1 of clinical development, though completed trials have been conducted at Phase 2. It is an investigational drug, meaning it has not received FDA approval and is still being studied for safety and efficacy in cancer patients.

What clinical trials is ZD6474 in?

ZD6474 has been studied in several completed clinical trials, including NCT00059722, which compared ZD6474 with ZD1839 in non-small cell lung cancer, and NCT00252746, a Phase IIa dose-finding study in non-small cell lung carcinoma. Other trials include NCT00071188 and NCT00659438.

Is ZD6474 the same as Zactima?

Yes, ZD6474 is also known as Zactima, as referenced in a clinical trial title for patients with castration-refractory metastatic prostate cancer. This alternative name is used in some research contexts, so readers searching for Zactima will find information about ZD6474.