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Part A: AZD8186 monotherapy

Phase 1

Advanced Castrate-resistant Prostate Cancer CRPC | Small molecule | Oncology |AstraZeneca PLC|Last Updated: May 29, 2020

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
CONTROLLEDBiomarker
Total Trials1
Total Enrollment147
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01884285AZD8186 First Time In Patient Ascending Dose StudyPHASE1 COMPLETED 147Jul 9, 2013Feb 7, 2020May 29, 202013 United States, Canada +2
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Study Endpoints
Primary Endpoints
Safety and tolerability
Routine safety assessments, throughout the period that patients receive AZD8186 up to 30 days following discont of last dose of study treatment.

Assess safety and tolerability of AZD8186 when given as monotherapy or in combination with abiraterone acetate (with prednisone) or with AZD2014 by measuring AEs, SAE (incl death), safety measures incl ECG, physical exam, pulse, blood pressure, weight, lab variables

Secondary Endpoints
Part A: The number of evaluable patients with dose limiting toxicities (DLTs).
DLTs assessed during the first 21 days of multiple dosing.
Part A, B, C + D: Antitumor activity of AZD8186 monotherapy or in combination
Every 12 weeks (non prostate patients) or every 6 weeks (prostate patients) from baseline up to disease progression or withdrawal of consent
Part A, B, C and D: Anti-tumour activity of AZD8186 monotherapy or in combination
PSA at Screening, Days 1, 8 & 15 then every 28 days, discontinuation of treatment (on average after 4 months), 30-day follow-up: CTC enumeration Days 1, 56 & 84, then every 12 weeks, at discontinuation (on average after 4 months).
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Study Design & Arms
AllocationNON_RANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Part A: AZD8186 monotherapyEXPERIMENTALPatients will receive a single dose on Day 1 followed by ongoing multiple dosing. The initial schedule will use intermittent dosing of AZD8186.
Part C2: AZD8186/abirateroneEXPERIMENTALPatients will receive a week of abiraterone acetate with prednisone followed by combination dosing with AZD8186.
Part D1: AZD8186 and AZD2014EXPERIMENTALCombination dosing with AZD8186 and AZD2014 both given on an intermittent schedule at escalating dose levels of each IMP for combination dose finding
Part B: AZD8186 monotherapyEXPERIMENTALPart B - multiple dosing of intermittent dose schedule
Part D2: AZD8186/ AZD2014EXPERIMENTALExpanded cohort of patients will be treated at a tolerated combination dose level established in Part D1
Part C1: AZD8186 & abirateroneEXPERIMENTALPatients will receive a week of abiraterone acetate with prednisone followed by combination dosing with AZD8186 at escalating doses of AZD8186 for the purpose of dose finding
Interventions
NameTypeDescription
Part A: AZD8186 monotherapyDRUGThe initial schedule will use intermittent dosing of AZD8186. Dose, frequency and schedule in subsequent cohorts may be modified in response to safety, tolerability, pharmacokinetic and preclinical data.
Part B: AZD8186 monotherapyDRUGPart B will be at a dose(s) and schedule(s) at or below from Part A
Part C1: Abiraterone acetate combination with AZD8186DRUGDose and schedule finding of AZD8186 added to approved labelled dose of abiraterone acetate (with prednisone).
Part D1: AZD2014 combination with AZD8186DRUGDose \& schedule finding of AZD8186 in combination with AZD2014
Part D2 AZD2014 combination with AZD8186DRUGCombination AZD8186/ AZD2014 dose expansion at dose determined in Part D1
Part C2: Abiraterone acetate combination with AZD8186DRUGDose expansion of AZD8186 at dose determined in Part C1 added to approved dose of abiraterone acetate (with prednisone)
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Eligibility Criteria
Age Range18 Years — 130 Years
SexALL
Healthy VolunteersNo
Study Sites13

Inclusion Criteria: * Provision of signed and dated, written informed consent prior to any study specific procedures * Male or female, aged 18 years and older * Histologically or cytologically proven diagnosis of prostate cancer, sqNSCLC, TNBC, or known PTEN-deficient solid malignancy, and is refra...

Countries:United StatesCanadaSpainUnited Kingdom
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