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ABT-263

Phase 2

Chronic Lymphocytic Leukemia | Small molecule | Oncology |AbbVie Inc.|Last Updated: Jun 13, 2023

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
RandomizedCONTROLLEDBiomarker
Total Trials3
Total Enrollment210
FDA Designations
No designations recorded
Clinical Trials (3)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01087151A Study of ABT-263 in Combination With Dose-Intensive Rituximab, or Dose-Intensive Rituximab Alone, in Previously Untreated Patients With B-Cell, Chronic Lymphocytic Leukemia (CLL)PHASE2 COMPLETED 118Aug 1, 2010Jun 1, 2012Nov 2, 2016103 United States, Australia +10
NCT00868413Study of ABT-263 When Administered in Combination With Either Fludarabine/Cyclophosphamide/Rituximab or Bendamustine/Rituximab in Relapsed or Refractory Chronic Lymphocytic LeukemiaPHASE1 COMPLETED 32Nov 1, 2009May 1, 2013Jun 7, 20136 United States
NCT00481091A Study of ABT-263 in Participants With Relapsed or Refractory Chronic Lymphocytic LeukemiaPHASE1 COMPLETED 60Jul 25, 2007May 12, 2022Jun 13, 202310 United States, Australia +2
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Study Endpoints
Primary Endpoints
Progression-free survival
From randomization to the first occurrence of progression, relapse, or death on study (approximately 40 months from First Patient In [FPI])
Assess the safety profile, characterize pharmacokinetics, and determine the MTD and recommended Phase 2 dose (RPTD) of ABT-263 when administered in combination with either FCR or BR in subjects with relapsed or refractory CLL.
Safety assessments = 1 wk, Pharmacokinetic (PK) Sampling = 1 wk for 1st 2 cycles, then, every other cycle starting Cycle 3 to Cycle 9, Determination of MTD & RPTD = Every 60 days
Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to Adverse Events (AEs)
From first dose of study drug to 30 days post-last dose. Participants enrolled in the 14/21-day cycle received a mean of 21.7 treatment cycles; participants enrolled in the 21/21-day cycle received a mean of 19.4 treatment cycles.

An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An SAE is one that: results in death, hospitalization, prolongation of hospitalization, or persistent or significant disability/incapacity; is life-threatening, a congenital anomaly, or other important medical event. Events were graded as 1=mild, 2=moderate, 3=severe, 4=life-threatening, or 5=death. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A treatment-emergent adverse event is defined as any adverse event with onset or worsening reported by a subject from the time that the first dose of study drug is administered until 30 days have elapsed following discontinuation of study drug administration. Deaths category included non treatment emergent deaths.

Phase 1: Number of Participants With DLTs in the Dose Escalation Phase
Cycle 1 (Up to 21 days) plus 7 days

DLTs were graded according to NCI CTCAE version 3.0 (grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life threatening; grade 5=death). Any of the following events, considered possibly or probably related to the administration of navitoclax, were considered a DLT: Grade 4 thrombocytopenia (\< 25,000/mm\^3); platelet counts \< 25,000/mm\^3, Grade 2 or higher bleeding associated with thrombocytopenia; all other Grade 3, 4 or 5 adverse events were considered a DLT. Exceptions included: Grade 3, 4 febrile neutropenia less than 7 days; Grade 3, 4 leukopenia; Grade 3, 4 lymphopenia; Grade 3 nausea, vomiting and/or diarrhea unless unresponsive to treatment; Grade 2 toxicity that requires dose modification or delay of \> 1 week.

Phase 1: Maximum Tolerated Dose (MTD) in the Dose Escalation Phase
Cycle 1 (Up to 21 days) plus 7 days

The MTD was defined as the dose at which 30% of participants experienced a DLT during the first cycle. DLTs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 (grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life threatening; grade 5=death). Any of the following events, considered possibly or probably related to the administration of navitoclax, were considered a DLT: Grade 4 thrombocytopenia (\< 25,000/mm\^3); platelet counts \< 25,000/mm\^3, Grade 2 or higher bleeding associated with thrombocytopenia; all other Grade 3, 4 or 5 adverse events were considered a DLT. Exceptions included: Grade 3, 4 febrile neutropenia less than 7 days; Grade 3, 4 leukopenia; Grade 3, 4 lymphopenia; Grade 3 nausea, vomiting and/or diarrhea unless unresponsive to treatment; Grade 2 toxicity that requires dose modification or delay of \> 1 week.

Phase 1: Recommended Phase 2 Dose (RPTD) Determined in the Dose Escalation Phase
Cycle 1 (Up to 21 days) plus 7 days

The RPTD was determined based on observed DLTs and/or determination of the MTD in phase 1. (See Outcome Measures 2 and 3 above for definition of DLT and MTD.)

Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Navitoclax
Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Phase 1: Maximum Observed Plasma Concentration (Cmax)
Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Phase 1: Area Under the Plasma Concentration-Time Curve From Time 0 to Hour 8 (AUC8)
Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Phase 1: Area Under the Plasma Concentration-Time Curve From Time 0 to Hour 24 (AUC24)
Cycle 1 Day 1: pre-dose, 2, 4, 6, 8, and 24 hours post-dose; Cycle 1 Days 14: pre-dose, 2, 4, 6, 8

The AUC24 was derived and reported from Cycle 1 Day 1 values and Cycle 1 Day 14 values; the pre-dose value taken on Day 14 was utilized as 24-hour timepoint on Day 14 to generate AUC24 for Day 14.

Phase 1: Cmax/Dose
Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Phase 1: AUC8/Dose
Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Phase 1: AUC24/Dose
Cycle 1 Day 1: pre-dose, 2, 4, 6, 8, and 24 hours post-dose; Cycle 1 Days 14: pre-dose, 2, 4, 6, 8

The AUC24 was derived and reported from Cycle 1 Day 1 values and Cycle 1 Day 14 values; the pre-dose value taken on Day 14 was utilized as 24-hour timepoint on Day 14 to generate AUC24 for Day 14.

Phase 1: Terminal Phase Elimination Rate Constant (β) for Navitoclax
Cycle 1 Day 1: pre-dose, 2, 4, 6, 8 hours post-dose
Phase 1: Terminal Phase Elimination Half-life (t1/2) of Navitoclax
Cycle 1 Day 1: pre-dose, 2, 4, 6, 8 hours post-dose

For t1/2, the harmonic mean and psuedo-standard deviation are used.

Phase 2: Number of Participants With TEAEs, SAEs, and Discontinuations Due to AEs
From first dose of study drug to 30 days post-last dose. Participants enrolled in Phase 2 received a mean of 15.6 treatment cycles.

An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An SAE is one that: results in death, hospitalization, prolongation of hospitalization, or persistent or significant disability/incapacity; is life-threatening, a congenital anomaly, or other important medical event. Events were graded as 1=mild, 2=moderate, 3=severe, 4=life-threatening, or 5=death. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A treatment-emergent adverse event is defined as any adverse event with onset or worsening reported by a subject from the time that the first dose of study drug is administered until 30 days have elapsed following discontinuation of study drug administration. Deaths category included non treatment emergent deaths.

Phase 2: Dose-Normalized Plasma Concentrations After Navitoclax Once Daily Dosing
Cycle 1 Day 1: 4-8 h postdose; Cycle 1 Day 15: predose; Cycle 3 Day 1: predose, 4-8 h postdose; Cycle 5 Day 1: predose, 4-8 h postdose; Cycle 7 Day 1: predose, 4-8 h postdose; Cycle 9 Day 1: predose, 4-8 h postdose
Secondary Endpoints
Overall response rate (ORR)
Approximately 40 months from FPI
Duration of response
Approximately 40 months from FPI
Complete response (CR) rate
Approximately 40 months from FPI
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Study Design & Arms
AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
AACTIVE_COMPARATOR -
BEXPERIMENTAL -
CEXPERIMENTAL -
Navitoclax 14/21 Day Cycle: 10 mgEXPERIMENTALNavitoclax 10 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle.
Navitoclax 14/21 Day Cycle: 110 mgEXPERIMENTALNavitoclax 110 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle.
Navitoclax 14/21 Day Cycle: 200 mgEXPERIMENTALNavitoclax 200 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle.
Navitoclax 14/21 Day Cycle: 250 mgEXPERIMENTALNavitoclax 250 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle.
Navitoclax 21/21 Day Cycle: 125 mgEXPERIMENTALNavitoclax 125 mg administered for 21 consecutive days to complete a 21-day cycle.
Navitoclax 21/21 Day Cycle: 200 mgEXPERIMENTALNavitoclax 200 mg administered for 21 consecutive days to complete a 21-day cycle.
Navitoclax 21/21 Day Cycle: 250 mgEXPERIMENTALNavitoclax 250 mg administered for 21 consecutive days to complete a 21-day cycle.
Navitoclax 21/21 Day Cycle: 300 mgEXPERIMENTALNavitoclax 300 mg administered for 21 consecutive days to complete a 21-day cycle.
Phase 2: Navitoclax 100 mgEXPERIMENTALNavitoclax 100 mg in participants with CLL who had relapsed following any (but no more than 5) prior myelosuppressive/chemotherapy treatment regimen(s).
Phase 2: Navitoclax 250 mgEXPERIMENTALNavitoclax 250 mg in participants with CLL who had relapsed following any (but no more than 5) prior myelosuppressive/chemotherapy treatment regimen(s).
Interventions
NameTypeDescription
ABT-263DRUGOral repeating dose
rituximabDRUGIntravenous repeating dose
FCRDRUGRituximab will be given by intravenous infusion for 1 day out of each 28 day cycle; Fludarabine will be given by intravenous infusion for 3 days out of each 28 day cycle; and Cyclophosphamide will be given by intravenous infusion for 3 days out of each 28 day cycle
BRDRUGRituximab will be given by intravenous infusion for 2 days out of each 28 day cycle and Bendamustine will be given by intravenous infusion for 2 days out of each 28 day cycle
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites103

Inclusion Criteria: * Previously untreated, CD20-positive B-cell CLL * ECOG performance status of 0 or 1 * Life expectancy \> 6 months * Willingness and capability to be accessible for follow-up until study termination or death * For patients of reproductive potential (both males and females), use ...

Countries:United StatesAustraliaBrazilCzechiaFranceIsraelItalyPolandPuerto RicoRussiaUkraineUnited KingdomGermany
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