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AZD2811

Phase 1

Advanced Solid Tumours | Small molecule | Oncology |AstraZeneca PLC|Last Updated: May 1, 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 Enrollment72
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT02579226A Phase I Study of Safety, Tolerability, and PK of AZD2811 in Patients With Advanced Solid Tumors.PHASE1 COMPLETED 72Oct 28, 2015Apr 3, 2020May 1, 20206 United States
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Study Endpoints
Primary Endpoints
The incidence of dose-limiting toxicites (DLTs)
Patients will be followed for either 21 or 28 days in Cycle 1 to determine the incidence of Dose Limiting Toxicities (DLTs).

Maximum Tolerated Dose (MTD) will be determined in Part A of the study by assessing the incidence of Dose Limiting Toxicities (DLTs), adverse events, and abnormal laboratory results. DLT is defined as: 1. Grade 4 neutropenia for \> 7 days, or febrile neutropenia. 2. Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with bleeding. 3. Concurrent Grade ≥3 total bilirubin, ALT or AST or alkaline phosphatase lasting \> 48 hours, or any change in liver function test results consistent with Hy's Law. 4. Grade ≥3 non-hematologic AE except: a) Grade 3 diarrhoea controlled within 4 days with standard supportive care, b) Grade 3 elevations in ALT/AST that return to meet initial eligibility criteria within 7 days of study drug interruption. 5. Inability to receive all doses in Cycle 1 due to treatment-related toxicity. 6. Non-haematologic toxicity of ≥ Grade 2 (at any time during treatment) that, in the judgment of the Investigator and the Medical Monitor, is dose limiting.

The incidence of adverse events
Patients will be followed for either 21 or 28 days in Cycle 1 to determine the incidence of adverse events

Maximum Tolerated Dose (MTD) will be determined in Part A of the study by assessing the incidence of Dose Limiting Toxicities (DLTs), adverse events, and abnormal laboratory results. At least 3 evaluable patients will be enrolled at each dose level (3+3 design) and will be evaluated for 21 or 28 days before escalation to the next dose level can occur. If one patient experiences a DLT, an additional 3 patients will be treated with the same dose. Therefore, a maximum of up to 6 patients may be enrolled per dose level.

The incidence of abnormal laboratory results
Patients will be followed for either 21 or 28 days in Cycle 1 to determine the incidence of abnormal laboratory results.

Maximum Tolerated Dose (MTD) will be determined in Part A of the study by assessing the incidence of Dose Limiting Toxicities (DLTs), adverse events, and abnormal laboratory results. At least 3 evaluable patients will be enrolled at each dose level (3+3 design) and will be evaluated for 21 or 28 days before escalation to the next dose level can occur. If one patient experiences a DLT, an additional 3 patients will be treated with the same dose. Therefore, a maximum of up to 6 patients may be enrolled per dose level.

Secondary Endpoints
Maximum plasma concentration (Cmax) of encapsulated AZD2811, released AZD2811, and AZD2811 metabolites
Blood will be taken from subjects in Part A Cycle 1/Day 1: pre-dose, 1, 2, 4, 6, 8, 24, and 48 hr post dose; and Day 4: pre-dose, 1, 2, 4, 6, 8, 24, 48, 96, 336, 360, and 504 hr post dose, and Cycle 2/Day 1 pre-dose and 2 hr post dose.
Time to maximum plasma concentration (tmax) for encapsulated AZD2811, released AZD2811, and AZD2811 metabolites.
Blood will be taken from subjects in Part A Cycle 1/Day 1: pre-dose, 1, 2, 4, 6, 8, 24, and 48 hr post dose; and Day 4: pre-dose, 1, 2, 4, 6, 8, 24, 48, 96, 336, 360, and 504 hr post dose, and Cycle 2/Day 1 pre-dose and 2 hr post dose.
Area under the plasma concentration-time curve from zero to the last measurable concentration [AUC(0-t)] for encapsulated AZD2811, released AZD2811, and AZD2811 metabolites.
Blood will be taken from subjects in Part A Cycle 1/Day 1: pre-dose, 1, 2, 4, 6, 8, 24, and 48 hr post dose; and Day 4: pre-dose, 1, 2, 4, 6, 8, 24, 48, 96, 336, 360, and 504 hr post dose.
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Study Design & Arms
AllocationNON_RANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Part AEXPERIMENTALPart A dose-escalation will evaluate the safety and tolerability of AZD2811 monotherapy at increasing doses in patients with advanced solid tumours. Patients will receive AZD2811 on Days 1 and 4 of a 28-day cycle or Day 1 only in cycles of either 21 or 28 days.
Part BEXPERIMENTALPart B will include patients with relapsed or refractory small-cell lung cancer (SCLC). Patients will receive AZD2811 monotherapy at the recommended Phase 2 dose (RP2D).
Interventions
NameTypeDescription
AZD2811DRUGThe study will be conducted in 2 parts, dose-escalation (A) and dose-expansion (B). All patients in both parts of the study with receive AZD2811.
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Eligibility Criteria
Age Range18 Years — 130 Years
SexALL
Healthy VolunteersNo
Study Sites6

Inclusion Criteria: Part A Dose Escalation: 1. Histological or cytological confirmation of a solid tumour and disease progression despite standard therapy(ies), or they must be intolerant to standard therapy(ies), or no standard therapy exists. 2. Patients must have received ≤3 prior chemotherapy ...

Countries:United States
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