Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
ABT-263 · 11 trials · 13 indications
Assess the oral bioavailability of Formulation B1, Formulation B2, Formulation C, and Formulation D relative to that of Formulation A being assessed in ongoing Phase 1/2a ABT-263 studies
• assess the safety profile of ABT-263 in combination with erlotinib; • study the pharmacokinetic interaction between ABT-263 and erlotinib; • determine the maximum tolerated dose (MTD) of ABT-263 when administered with erlotinib
• assess the safety profile of ABT-263 in combination with irinotecan; • study the pharmacokinetic interaction between ABT-263 and irinotecan; • determine the maximum tolerated dose (MTD) of ABT-263 when administered with irinotecan.s
• assess the safety profile of ABT-263 as a monotherapy
Evaluate safety at the defined recommended Phase 2 dose (RPTD) and schedule of ABT-263 in combination with Paclitaxel
Evaluate preliminary data regarding objective response rate (ORR), progression free survival (PFS), time to tumor progression (TTP), overall survival (OS), duration of overall response, and, ECOG performance status
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.
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.
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.
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.)
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.
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.
For t1/2, the harmonic mean and psuedo-standard deviation are used.
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.
1a: Determination of dose limiting toxicity (DLT) and maximum tolerated dose (MTD) under a 14/21 day dosing schedule
Phase 1b: Determination of ABT-263 dose limiting toxicity (DLT) and maximum tolerated dose (MTD) under a 21 day continuous dosing schedule.
Phase 2a: Continued assessment of the safety profile of ABT-263 at the Recommended Phase 2 Dose (RPTD) and schedule under a 21 day continuous dosing.
Phase 2a: Assessment of the preliminary efficacy signals of ABT-263, including biomarker assessment, at the Recommended Phase 2 Dose (RPTD) and schedule under a 21 day continuous dosing.
Continued assessment of the safety profile of ABT-263.
Continued assessment of the preliminary efficacy signals of ABT-263.
| Arm | Type | Description |
|---|---|---|
| A | ACTIVE_COMPARATOR | - |
| B | EXPERIMENTAL | - |
| C | EXPERIMENTAL | - |
| ABT-263 + etoposide/cisplatin | EXPERIMENTAL | - |
| Sequence I | EXPERIMENTAL | - |
| Sequence II | EXPERIMENTAL | - |
| Sequence III | EXPERIMENTAL | - |
| Sequence IV | EXPERIMENTAL | - |
| Sequence V | EXPERIMENTAL | - |
| Sequence VI | EXPERIMENTAL | - |
| Sequence VII | EXPERIMENTAL | - |
| Sequence VIII | EXPERIMENTAL | - |
| Sequence IX | EXPERIMENTAL | - |
| Sequence X | EXPERIMENTAL | - |
| Sequence XI | EXPERIMENTAL | - |
| Sequence XII | EXPERIMENTAL | - |
| Sequence XIII | EXPERIMENTAL | - |
| Sequence XIV | EXPERIMENTAL | - |
| Sequence XVI | EXPERIMENTAL | - |
| Sequence XV | EXPERIMENTAL | - |
| Arm A (ABT-263 and erlotinib) | EXPERIMENTAL | - |
| Arm B (ABT-263 and irinotecan) | EXPERIMENTAL | - |
| Arm C (ABT-263 monotherapy) | EXPERIMENTAL | - |
| gemcitabine +ABT-263 | EXPERIMENTAL | - |
| ABT-263 + rituximab | EXPERIMENTAL | - |
| Paclitaxel and ABT-263 | EXPERIMENTAL | - |
| Navitoclax 14/21 Day Cycle: 10 mg | EXPERIMENTAL | Navitoclax 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 mg | EXPERIMENTAL | Navitoclax 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 mg | EXPERIMENTAL | Navitoclax 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 mg | EXPERIMENTAL | Navitoclax 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 mg | EXPERIMENTAL | Navitoclax 125 mg administered for 21 consecutive days to complete a 21-day cycle. |
| Navitoclax 21/21 Day Cycle: 200 mg | EXPERIMENTAL | Navitoclax 200 mg administered for 21 consecutive days to complete a 21-day cycle. |
| Navitoclax 21/21 Day Cycle: 250 mg | EXPERIMENTAL | Navitoclax 250 mg administered for 21 consecutive days to complete a 21-day cycle. |
| Navitoclax 21/21 Day Cycle: 300 mg | EXPERIMENTAL | Navitoclax 300 mg administered for 21 consecutive days to complete a 21-day cycle. |
| Phase 2: Navitoclax 100 mg | EXPERIMENTAL | Navitoclax 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 mg | EXPERIMENTAL | Navitoclax 250 mg in participants with CLL who had relapsed following any (but no more than 5) prior myelosuppressive/chemotherapy treatment regimen(s). |
| Phase 1 and Phase 2a | EXPERIMENTAL | - |
| Phase 1a and 1b | EXPERIMENTAL | Relapsed or refractory lymphoid malignancies |
| Arm A (Phase 2a) | EXPERIMENTAL | Relapsed or refractory follicular lymphoma |
| Arm B (Phase 2a) | EXPERIMENTAL | Relapsed or refractory mantle cell, peripheral T-cell, cutaneous T-cell lymphoma including mycosis fungoides and Sezary syndrome, or other indolent B-cell lymphomas such as marginal zone lymphoma |
| Extension Study | EXPERIMENTAL | Relapsed or refractory follicular lymphoma or Relapsed or refractory mantle cell, peripheral T-cell, cutaneous T-cell lymphoma including mycosis fungoides and Sezary syndrome, or other indolent B-cell lymphomas such as marginal zone lymphoma |
| Name | Type | Description |
|---|---|---|
| ABT-263 | DRUG | Oral repeating dose |
| rituximab | DRUG | Intravenous repeating dose |
| FCR | DRUG | Rituximab 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 |
| BR | DRUG | Rituximab 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 |
| etoposide/cisplatin | DRUG | etoposide = 100 mg/m2 Days 1-3 of each Cycle; Max duration 6 cycles. cisplatin = 75 mg/m2 Day 1 of each Cycle; Max duration 6 cycles |
| erlotinib | DRUG | 150 mg of erlotinib is taken orally once daily. |
| irinotecan (3-week schedule) | DRUG | 180 mg/m2 over 90 minutes, irinotecan will be given by intravenous infusion on Day 1 of each 21 day cycle. Note - The dose and schedule is subject to change based on the toxicities observed. |
| irinotecan (weekly schedule) | DRUG | 75 mg/m2 over 45 minutes, irinotecan will be given by intravenous infusion on Days 1 and 8 of each 21 day cycle. Note - The dose and schedule is subject to change based on the toxicities observed. |
| gemcitabine | DRUG | Gemcitabine 1000 mg/m2 will be given by intravenous infusion on Day 1 and Day 8 of each 21 day cycle. Gemcitabine 1000 mg/m2 will be given by intravenous infusion on days 1, 8 and 15 of each 28 day cycle. |
| paclitaxel | DRUG | 175 mg/m2 over 3 hours of paclitaxel will be given by intravenous infusion on Day 1 of each 21 day cycle. Note - The dose and schedule is subject to change based on the toxicities observed. |
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 ...
ABT-263 is an investigational small molecule being studied for the treatment of chronic lymphocytic leukemia, small cell lung cancer, CD20-positive lymphoid malignancies, chronic lymphoid leukemia, solid tumors, and lymphoid malignancy. It is being developed by AbbVie Inc. and is currently in Phase 1 clinical development.
ABT-263 is a small molecule that targets BCL-2 family proteins, which are involved in regulating apoptosis. By inhibiting these proteins, ABT-263 is designed to promote cell death in cancer cells. This mechanism is being evaluated in clinical trials for various hematologic malignancies and solid tumors.
ABT-263 is being developed by AbbVie Inc., a biopharmaceutical company traded on the New York Stock Exchange under the ticker ABBV. The drug is currently in Phase 1 clinical trials for multiple oncology indications, including chronic lymphocytic leukemia and small cell lung cancer.
ABT-263 is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA. Four clinical trials have been completed, with a total enrollment of 210 participants, all of which were uncontrolled, non-randomized, and open-label studies.
ABT-263 has completed four clinical trials. NCT00406809 studied relapsed or refractory lymphoid malignancies. NCT00481091 evaluated relapsed or refractory chronic lymphocytic leukemia. NCT00868413 tested ABT-263 in combination with fludarabine/cyclophosphamide/rituximab or bendamustine/rituximab. NCT01087151 assessed ABT-263 with dose-intensive rituximab in previously untreated B-cell chronic lymphocytic leukemia.
ABT-263 is also known as navitoclax. It is an investigational BCL-2 inhibitor being developed by AbbVie Inc. for the treatment of various cancers, including chronic lymphocytic leukemia and small cell lung cancer. The drug is currently in Phase 1 clinical trials.