Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Veliparib (ABT-888), ABT-888, velaparib
Veliparib · 26 trials · 35 indications
Overall survival is defined as the time from the date that the participant was randomized to the date of the participant's death. Overall survival was estimated using Kaplan-Meier methodology. Participants still alive at the data cut-off date were censored at the date they were last known to be alive.
Time to death for a given subject will be defined as the number of days from the date that the subject was randomized to the date of the subject's death.
Time to PFS is defined as the number of days from the date the participant was randomized to the date the participant experiences radiographic disease progression (as determined by the investigators), or to the date of death (all causes of mortality) if disease progression is not reached. All events of disease progression occurring on or before the Primary Analysis Cutoff date of 05 April 2019 were to be included, regardless of whether the event occurred while the participant was still taking study drug or had previously discontinued study drug. PFS was estimated for each treatment group using Kaplan-Meier methodology.
Pathological complete response (pCR) in the breast tissue and the lymph node tissue will be assessed upon completion of pre-operative systemic therapy and definitive surgery.
PFS was defined as the number of days from the date the participant was randomized to the date the participant experienced an event of disease progression or death, whichever occurred first. All events of disease progression were included, whether the participant was still taking or had discontinued study drug. Events of death were included for participants who had not experienced an event of disease progression, if the death occurred within 8 weeks of the last evaluable disease progression assessment. If the participant did not have an event of disease progression and the participant had not died as defined above, data were censored at the date of the participant's last evaluable disease progression assessment. The PFS distribution was estimated using Kaplan-Meier methodology. Point estimates and 95% confidence intervals (95% CIs) for the PFS distribution quartiles are provided.
Overall survival was defined as the number of days from the date of randomization to the date of death. All events of death were included, regardless of whether the event occurred while the participant was still taking study treatment or after treatment was discontinued. If a participant had not died, the data were censored at the date the participant was last known to be alive.
A DLT was defined as any of the following drug-related toxicities, graded according to the Common Toxicity Criteria for Adverse Events (CTCAE), V.4.0: 1. Events associated with treatment delay \>14 days in initiating Cycle 2 therapy: Grade 4 thrombocytopenia, neutropenia, or febrile neutropenia, or Grade 3 febrile neutropenia with fever for \> 7 days 2. Grade ≥ 3 non-hematologic toxicity with ≥ 2 grade increase from baseline and attributed to veliparib treatment, excluding nausea or vomiting for ≤ 48 hours or inadequately treated, electrolyte abnormalities resolving in ≤ 24 hours, hypersensitivity reactions or alopecia 3. Grade 2 non-hematologic toxicity of ≥ 2 grade increase from baseline, attributed to veliparib treatment requiring delay of \>14 days in initiation of Cycle 2 4. Any toxicity of ≥ 2-grade increase from baseline, attributed to veliparib and requiring a dose modification in Cycle 1 or omission of carboplatin, \>1 daily etoposide dose, or \>30% veliparib doses in Cycle 1
Plasma concentrations of veliparib were determined using a validated online solid-phase extraction followed by high-performance liquid chromatography with tandem mass spectrometric detection (HPLC LC-MS/MS). The lower limit of quantitation (LLOQ) for veliparib was established at ≥ 1.05 ng/mL.
Plasma concentrations of veliparib were determined using a validated online solid-phase extraction followed by high-performance liquid chromatography with tandem mass spectrometric detection (HPLC LC-MS/MS). The lower limit of quantitation (LLOQ) for veliparib was established at ≥ 1.05 ng/mL.
The area under the plasma concentration-time curve from time 0 to 8 hours post-dose for veliparib was estimated using non-compartmental methods.
The area under the plasma concentration-time curve from time 0 to 12 hours post-dose for veliparib was estimated using non-compartmental methods. AUC(0-12) was calculated by assuming the concentration at 12 hours post-dose was the same as the pre-dose concentration.
Plasma concentrations of veliparib were determined using a validated online solid-phase extraction followed by high-performance liquid chromatography with tandem mass spectrometric detection (HPLC LC-MS/MS). The lower limit of quantitation (LLOQ) for veliparib was established at ≥ 1.05 ng/mL. Dose normalized Cmax is calculated as Cmax / veliparib dose in mg.
The area under the plasma concentration-time curve from time 0 to 8 hours post-dose for veliparib was estimated using non-compartmental methods. Dose normalized AUC(0-8) is calculated as AUC(0-8) / veliparib dose in mg.
The area under the plasma concentration-time curve from time 0 to 12 hours post-dose for veliparib was estimated using non-compartmental methods. AUC(0-12) was calculated by assuming the concentration at 12 hours post-dose was the same as the pre-dose concentration. Dose normalized AUC(0-12) is calculated as AUC(0-12) / veliparib dose in mg.
Etoposide plasma concentrations were determined using liquid chromatography with tandem mass spectrometric detection with a lower limit of quantitation 160 ng/mL.
Etoposide plasma concentrations were determined using liquid chromatography with tandem mass spectrometric detection with a lower limit of quantitation 160 ng/mL.
The area under the plasma concentration-time curve from 0 to the last measurable concentration (24 hours) of etoposide was estimated using using non-compartmental methods.
The area under the plasma concentration-time curve from 0 to infinity for etoposide was estimated using using non-compartmental methods.
The terminal half-life of etoposide was estimated using using non-compartmental methods. Values reported represent the harmonic mean ± pseudo-standard deviation.
Etoposide plasma concentrations were determined using liquid chromatography with tandem mass spectrometric detection with a lower limit of quantitation 160 ng/mL. Dose normalized Cmax is calculated as Cmax / etoposide dose in mg/m².
The area under the plasma concentration-time curve from 0 to the last measurable concentration (24 hours) of etoposide was estimated using using non-compartmental methods. Dose normalized AUC(0-t) is calculated as AUC(0-t) / etoposide dose in mg/m².
The area under the plasma concentration-time curve from 0 to infinity for etoposide was estimated using using non-compartmental methods. Dose normalized AUC(0-∞) is calculated as AUC(0-∞) / etoposide dose in mg/m².
Progression-free survival (PFS) is defined as the time from the date of randomization to the date of earliest radiographic disease progression or death provided no radiographic disease progression occurred. If a participant did not have an event of disease progression and had not died on or prior to the cutoff for PFS analysis, the participant's data was censored at the date of their last disease assessment or randomization date provided participant did not have any post-baseline disease assessment. Disease assessments were performed using computed tomography according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Progressive Disease (PD) was defined as at least a 20% increase in the size of target lesions and an absolute increase of at least 5 mm taking as reference the smallest lesion size recorded since the treatment started (baseline or after), or the appearance of one or more new lesions.
Cmax, Tmax ,and AUC, and safety parameters
The following pharmacokinetic parameters will be analyzed: Tmax, the terminal phase elimination rate constant (β), the natural logarithms of Cmax, AUCt and AUC∞.
Blood pressure, Heart rate
Hematology, Chemistry, Urinalysis
Assess the relative bioavailability of Formulation A, Formulation B and Formulation C with or without food measured using area under the plasma concentration-time curve (AUC), the maximum observed plasma concentration (Cmax), and time to Cmax (Tmax).
This is performed to assess if ABT-888 combined with temozolomide has activity in patients with prostate cancer as reflected by the prostate-specific antigen (PSA).
| Arm | Type | Description |
|---|---|---|
| Veliparib + Carboplatin + Paclitaxel | EXPERIMENTAL | Participants received 120 mg veliparib twice a day (BID) on Days -2 to 5 (7 days), carboplatin at an area under the curve (AUC) of 6 mg/mL\*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles. After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred. |
| Investigator's Choice Chemotherapy | ACTIVE_COMPARATOR | Participants received Investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles: * Carboplatin AUC 6 mg/mL\*min + paclitaxel 200 mg/m² * Cisplatin 75 mg/m² + pemetrexed 500 mg/m² * Carboplatin AUC 6 or AUC 5 mg/mL\*min + pemetrexed 500 mg/m² After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred. |
| Placebo + Carboplatin + Paclitaxel | PLACEBO_COMPARATOR | Participants received placebo orally BID on Days -2 to 5 (7 consecutive days) of each 21-day cycle and carboplatin at an AUC 6 mg/mL/min and paclitaxel 200 mg/m² by IV infusion on Day 1 of each 21-day cycle for up to a maximum 6 cycles of treatment, until treatment toxicity which, in the Investigator's opinion, prohibited further therapy, or until radiographic progression. |
| Veliparib Placebo with Carboplatin and Paclitaxel | ACTIVE_COMPARATOR | Placebo capsules for veliparib (120 mg) administered by mouth twice daily (BID) on Days -2 through 5 of a 21-day cycle. Carboplatin administered intravenously over approximately 15 to 30 minutes at AUC 6 mg/ml/min immediately following paclitaxel infusion on Day 1 of every cycle. Paclitaxel administered intravenously over approximately 1 hour at a dose of 80 mg/m² on Days 1, 8, and 15 of every cycle. |
| Veliparib with Carboplatin and Paclitaxel | EXPERIMENTAL | Veliparib capsules (120 mg) administered by mouth twice daily (BID) on Days -2 through 5 of a 21-day cycle. Carboplatin administered intravenously over approximately 15 to 30 minutes at AUC 6 mg/ml/min immediately following paclitaxel infusion on Day 1 of every cycle. Paclitaxel administered intravenously over approximately 1 hour at a dose of 80 mg/m² on Days 1, 8, and 15 of every cycle. |
| Arm A | ACTIVE_COMPARATOR | Veliparib + carboplatin + paclitaxel followed by doxorubicin/cyclophosphamide (AC) |
| Arm C | PLACEBO_COMPARATOR | Placebo + placebo + paclitaxel followed by AC. |
| Arm B | PLACEBO_COMPARATOR | Placebo + carboplatin + paclitaxel followed by AC |
| Veliparib + modified FOLFIRI ± bevacizumab | EXPERIMENTAL | Dosing of oral veliparib (200 mg) began 2 days prior to the start of FOLFIRI and continued twice a day (BID) for a total of 7 consecutive days. At the discretion of the Investigator, bevacizumab (5 mg/kg) could be administered intravenously (IV) immediately preceding FOLFIRI. Modified FOLFIRI was administered as irinotecan 180 mg/m\^2 (90-minute infusion ± 30 minutes); leucovorin 400 mg/m\^2 (90-minute infusion ± 30 minutes); and saline bolus (up to 15-minute infusion) immediately followed by fluorouracil 2400 mg/m\^2 (46-hour continuous infusion ± 4 hours) starting on Day 1 of each 14-day cycle. |
| Placebo + FOLFIRI ± bevacizumab | PLACEBO_COMPARATOR | Dosing of oral placebo (200 mg) began 2 days prior to the start of FOLFIRI and continued twice a day (BID) for a total of 7 consecutive days. At the discretion of the Investigator, bevacizumab (5 mg/kg) could be administered intravenously (IV) immediately preceding FOLFIRI. Standard FOLFIRI was administered as irinotecan 180 mg/m\^2 (90-minute infusion ± 30 minutes); leucovorin 400 mg/m\^2 (90-minute infusion ± 30 minutes); and fluorouracil bolus 400 mg/m\^2 (up to 15-minute infusion) immediately followed by fluorouracil 2400 mg/m\^2 (46-hour continuous infusion ± 4 hours) on Day 1 of each 14-day cycle. |
| Veliparib 200 mg BID + WBRT | EXPERIMENTAL | Participants received veliparib 200 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays. |
| Veliparib 50 mg BID + WBRT | EXPERIMENTAL | Participants received veliparib 50 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays. |
| Placebo BID + WBRT | PLACEBO_COMPARATOR | Participants received placebo twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays. |
| veliparib and carboplatin and paclitaxel | EXPERIMENTAL | Veliparib on Days 1-7 and carboplatin and paclitaxel on Day 3 of a 21 day cycle |
| placebo and carboplatin and paclitaxel | PLACEBO_COMPARATOR | Placebo on Days 1-7 and carboplatin and paclitaxel on Day 3 of a 21 day cycle |
| Veliparib with Temozolomide | EXPERIMENTAL | Veliparib 40 mg twice daily (BID) Days 1 through 7 plus TMZ 150 to 200 mg/m\^2 QD Days 1 through 5 in each 28-day cycle. |
| Placebo with Carboplatin and Paclitaxel | PLACEBO_COMPARATOR | Placebo BID Days 1 through 7 plus carboplatin target area under the curve (mg•min/mL) (AUC) 6 administered on Day 3 of each 21-day cycle and paclitaxel 175 mg/m\^2 administered on Day 3 of each 21-day cycle. |
| Placebo for ABT-888 BID + TMZ QD | PLACEBO_COMPARATOR | Placebo for ABT-888 twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days. |
| ABT-888 20 mg BID + TMZ QD | ACTIVE_COMPARATOR | ABT-888 20 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days. |
| ABT-888 40 mg BID + TMZ QD | ACTIVE_COMPARATOR | ABT-888 40 mg twice daily (BID) for 7 days every 28 days plus temozolomide (TMZ; by body surface area) 150 mg/m2 once daily (QD) for 5 days every 28 days. |
| Veliparib and nivolumab with platinum doublet chemotherapy | EXPERIMENTAL | Veliparib and nivolumab in combination with platinum doublet chemotherapy (carboplatin/paclitaxel or carboplatin/pemetrexed) |
| Veliparib with platinum doublet chemotherapy | EXPERIMENTAL | Veliparib in combination with platinum doublet chemotherapy (carboplatin/paclitaxel or carboplatin/pemetrexed) |
| veliparib (ABT-888) | EXPERIMENTAL | - |
| Phase 1: Veliparib + Carboplatin + Etoposide | EXPERIMENTAL | Participants in Phase 1 will be sequentially assigned to ascending dose levels of veliparib in combination with carboplatin/etoposide for up to four 21-day cycles. Participants without evidence of disease progression will continue on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity. |
| Phase 2: Veliparib + Carboplatin + Etoposide -> Veliparib | EXPERIMENTAL | Participants will receive veliparib 240 mg in combination with carboplatin/etoposide for four to six 21-day cycles followed by veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity. |
| Phase 2: Veliparib + Carboplatin + Etoposide -> Placebo | EXPERIMENTAL | Participants will receive veliparib 240 mg in combination with carboplatin/etoposide for four to six 21-day cycles followed by placebo monotherapy continuous dosing (21-day cycles) until disease progression or unacceptable toxicity occurs. |
| Phase 2: Placebo + Carboplatin + Etoposide -> Placebo | ACTIVE_COMPARATOR | Participants will receive placebo in combination with carboplatin/etoposide for four to six 21-day cycles followed by placebo monotherapy continuous dosing (21-day cycles) until disease progression or unacceptable toxicity occurs. |
| Arm A - Veliparib Monotherapy | EXPERIMENTAL | Subjects in this arm will be dosed with Veliparib continuous dosing. |
| Arm B - Veliparib in Combination with Carboplatin & Paclitaxel | EXPERIMENTAL | Subjects enrolled will receive Veliparib in combination with Carboplatin and Paclitaxel and have an option to move to Veliparib monotherapy. |
| Arm C Veliparib in Combination with Modified FOLFIRI | EXPERIMENTAL | Subjects will be given Veliparib in combination with modified FOLFIRI. The subject will have the opportunity to receive Veliparib as monotherapy. |
| Sequence Group A | EXPERIMENTAL | 200 mg Veliparib |
| Sequence Group B | EXPERIMENTAL | 400 mg Veliparib |
| Sequence Group C | PLACEBO_COMPARATOR | Placebo |
| Combination: veliparib, gemcitabine, and IMRT | EXPERIMENTAL | - |
| Veliparib formulation A | EXPERIMENTAL | veliparib formulation A |
| Veliparib formulation B | EXPERIMENTAL | Veliparib formulation B |
| Veliparib formulation C | EXPERIMENTAL | veliparib formulation C |
| veliparib and capecitabine and radiation | EXPERIMENTAL | Veliparib on days 1-7, capecitabine and radiation on days 1-5 |
| Arm D | EXPERIMENTAL | - |
| Veliparib and FOLFIRI | EXPERIMENTAL | Veliparib in combination with FOLFIRI regimen. |
| Arm 1 | EXPERIMENTAL | - |
| 1 | EXPERIMENTAL | This is an open label study; therefore, there are no numbered/labeled study arms. This is a dose escalation study, ABT-888 dose will be escalated in conjunction with two schedules of whole brain radiation therapy (WBRT). Subjects may be treated WBRT for 3 weeks (15 days) or 2 weeks (10 days). |
| Open Label | EXPERIMENTAL | Within each dose level, subjects are treated with the same regimen/doses of ABT-888 and TMZ. |
| Name | Type | Description |
|---|---|---|
| Paclitaxel | DRUG | Administered by Intravenous infusion on Day 1 of each 21-day cycle |
| Carboplatin | DRUG | Administered by Intravenous infusion on Day 1 of each 21-day cycle |
| Cisplatin | DRUG | Administered by Intravenous infusion on Day 1 of each 21-day cycle |
| Veliparib | DRUG | Oral capsule, administered twice daily for 7 days in each 21-day cycle |
| Pemetrexed | DRUG | Administered by Intravenous infusion on Day 1 of each 21-day cycle |
| Placebo to veliparib | DRUG | Capsules taken orally twice a day, 12 hours apart. |
| Veliparib Placebo | DRUG | Supplied as 40 mg, 50 mg, or 100 mg capsules for oral administration twice daily (BID) on Days -2 through 5 of a 21-day cycle. |
| Cyclophosphamide | DRUG | Cyclophosphamide |
| Placebo | DRUG | Placebo for Carboplatin |
| Doxorubicin | DRUG | Doxorubicin |
| Modified FOLFIRI | DRUG | Irinotecan 180 mg/m\^2 (90-minute infusion ± 30 minutes); leucovorin 400 mg/m\^2 (90-minute infusion ± 30 minutes); and saline bolus (up to 15-minute infusion) on Day 1 of each 14-day cycle |
| FOLFIRI | DRUG | Irinotecan 180 mg/m\^2 (90-minute infusion ± 30 minutes); leucovorin 400 mg/m\^2 (90-minute infusion ± 30 minutes); and fluorouracil bolus 400 mg/m\^2 (up to 15-minute infusion) on Day 1 of each 14-day cycle |
| Bevacizumab | DRUG | At the discretion of the Investigator, 5 mg/kg may be administered intravenously immediately preceding FOLFIRI dosing |
| Fluorouracil infusion | DRUG | 2400 mg/m\^2 (46-hour continuous infusion ± 4 hours) starting on Day 1 of each 14-day cycle |
| Whole brain radiation therapy | RADIATION | 30.0 grays (Gy) of WBRT given in 10 daily fractions of 3.0 Gy each, excluding weekends and holidays |
| Temozolomide | DRUG | - |
| ABT-888 | DRUG | Arm-A subjects will be given ABT-888 on Days 1 -7 every 28 days orally |
| pegylated liposomal doxorubicin | DRUG | Arm B subjects randomized to pegylated liposomal doxorubicin on Day 1, every 28 days intravenously. |
| nivolumab | DRUG | intravenous; administered on Day 1 via infusion in a 21-day cycle |
| Etoposide | DRUG | Administered by intravenous infusion on Days 1 to 3 of every 21-day cycle over approximately 60 minutes at 100 mg/m². |
| veliparib (ABT-888) | DRUG | Subjects will be given veliparib twice daily on Days 1-28 every 28 days orally. |
| Gemcitabine | DRUG | - |
| Intensity modulated radiation therapy | RADIATION | - |
| capecitabine | DRUG | see arm description |
| radiation | RADIATION | see arm description |
Inclusion Criteria: * Subject must be ≥ 18 years of age with life expectancy \> 12 weeks. * Subject must have cytologically or histologically confirmed advanced or metastatic non-squamous NSCLC and are current or former smokers. * Subject must have NSCLC that is not amenable to surgical resection o...
Top 20 of 87 competitors
Veliparib is an investigational small molecule PARP inhibitor being developed by AbbVie Inc. (ticker: ABBV) for oncology indications. It has been studied in advanced solid tumors, brain metastases from non-small cell lung cancer, breast cancer, gastric cancer, locally advanced rectal cancer, and metastatic breast cancer. It is not approved and remains in clinical development.
Veliparib targets PARP1, PARP2, and PARP3, enzymes involved in DNA repair. By inhibiting these targets, veliparib interferes with DNA damage repair mechanisms in cancer cells. This mechanism is being explored in solid tumors and other malignancies, often in combination with chemotherapy or immunotherapy.
Veliparib is being developed by AbbVie Inc., which trades under the ticker ABBV. AbbVie is the sponsor of the clinical trials evaluating veliparib in various cancer types, including non-small cell lung cancer, ovarian cancer, colorectal cancer, and small cell lung cancer.
Veliparib is in Phase 1 clinical development. It is an investigational agent and has not been approved by the FDA or any regulatory authority. The reported trials include Phase 1 and Phase 2 studies, all of which are completed, with no active trials currently listed.
Veliparib has been evaluated in completed clinical trials including NCT02944396 (Phase 1 in non-small cell lung cancer), NCT02483104 (Phase 1 in ovarian cancer), NCT02305758 (Phase 2 in metastatic colorectal cancer), and NCT02289690 (Phase 1 in small cell lung cancer). These trials are all completed and no active trials are reported.
Yes, Veliparib is also known as ABT-888. ABT-888 is an alternative name for the same investigational compound. Both names refer to the PARP inhibitor being developed by AbbVie Inc. for oncology indications.