Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Adenosine

Poly(ADP-ribose) Polymerase Inhibitors

Veliparib

Tubulin Modulators

Antimitotic Agents

Enzyme Inhibitors

Participants will receive placebo to veliparib orally twice a day in combination with carboplatin/paclitaxel for six 21-day cycles followed by placebo monotherapy continuous dosing for an additional thirty 21-day cycles.

Participants will receive 150 mg veliparib orally twice a day in combination with carboplatin/paclitaxel for six 21-day cycles followed by placebo monotherapy continuous dosing for an additional thirty 21-day cycles.

Participants will receive 150 mg veliparib orally twice a day in combination with carboplatin/paclitaxel for six 21-day cycles followed by 300/400 mg veliparib monotherapy orally twice a day for an additional thirty 21-day cycles.

Administered by intravenous infusion, either 80 mg/m² of body-surface area (BSA) on Days 1, 8, and 15 of each 21-day cycle (weekly dosing), or 175 mg/m² of BSA on Day 1 of each 21-day cycle (3-week dosing).

Administered by intravenous infusion at an area under the curve (AUC) of 6 mg/mL/min every 3 weeks.

Placebo to Veliparib

AbbVie Inc.

The primary objective of the study was to evaluate whether progression-free survival (PFS) was prolonged with the addition of veliparib to standard platinum-based chemotherapy (carboplatin/paclitaxel \[C/P\]) and continued as maintenance therapy compared with chemotherapy alone.

Participants were randomized in a 1:1:1 ratio to one of three arms. Randomization in the entire population was stratified according to the timing of surgery and residual disease status (any residual disease after primary surgery vs. no residual disease after primary surgery vs. interval surgery) and the paclitaxel schedule (weekly vs. every 3 -weeks), stage of disease (III vs. IV), geographic region (Japan vs. North America and rest of world \[ROW\]), and germline breast cancer susceptibility gene (BRCA) mutation status (positive versus negative or Unknown).

Cytoreductive surgery could be performed before randomization and the initiation of study treatment (primary) or after 3 cycles of study treatment (interval). The weekly or every-3-week paclitaxel schedule and the choice of primary or interval cytoreductive surgery were determined at the discretion of the investigator.

The primary objective was evaluated in the BRCA-deficient cohort, participants with homologous recombination deficiency (HRD), and the intention-to-treat (ITT) population. These populations were sequentially inclusive, with the HRD population including the BRCA-deficient population, and the ITT population including the HRD and BRCA-deficient populations. The BRCA-deficient population was defined as participants with either a germline (gBRCA) and/or tissue-based (tBRCA) deleterious or suspected deleterious mutation in BRCA1 or BRCA2 confirmed by centralized testing. The HRD population was defined as participants with HRD tumors based on HRD score or presence of a deleterious or suspected deleterious mutation in BRCA1 or BRCA2 as determined by centralized testing.

Veliparib With Carboplatin and Paclitaxel and as Continuation Maintenance Therapy in Adults With Newly Diagnosed Stage III or IV, High-grade Serous, Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

A Phase 3 Placebo-Controlled Study of Carboplatin/Paclitaxel With or Without Concurrent and Continuation Maintenance Veliparib (PARP Inhibitor) in Subjects With Previously Untreated Stages III or IV High-Grade Serous Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death if disease progression was not reached. If the participant did not have an event of disease progression or death prior to the analysis cut-off date, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. The analysis of PFS occurred when the protocol-specified number of PFS events was reached.

Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions.

PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death if disease progression was not reached. If the participant did not have an event of disease progression or death, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. The primary analysis of PFS occurred when the protocol-specified number of PFS events was reached and was performed in 3 sequentially inclusive populations.

Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions.

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PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death (all causes of mortality) if disease progression was not reached. If the participant did not have an event of disease progression according to RECIST criteria (as or death, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method.

Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions.

The primary analysis of PFS occurred when the protocol-specified number of PFS events was reached.

OS is defined as the time from the day the participant was randomized to the date of death. All events of death will be included, regardless of whether the event occurs while the participant is still taking study drug, or after discontinuation of study drug. If a participant has not died, then the data will be censored at the date the participant is last known to be alive.

The final analysis of OS will occur when the pre-specified number of events has occurred in the ITT and HRD populations.

The Disease Related Symptom score is a subset of the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Ovarian Symptom Index-18 (NFOSI-18), which evaluates nine symptoms related to ovarian cancer. The NFOSI-18 DRS score ranges from 0 to 36, with higher scores indicating a lower burden of symptoms and a score of 0 being severely symptomatic. A 3-point difference was defined as clinically meaningful. A positive change from Baseline indicates improvement.

Change from Baseline was calculated using a used a mixed-model for repeated measures (MMRM) with treatment, stratification factors of residual disease and stage of disease, time point and treatment-by-time point interaction as fixed effect factors, and Baseline DRS score as a covariate.

DRS was not included in the fixed-sequence testing procedure.

The Disease Related Symptom score is a subset of the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Ovarian Symptom Index-18 (NFOSI-18), which evaluates nine symptoms related to ovarian cancer. The NFOSI-18 DRS score ranges from 0 to 36, with higher scores indicating a lower burden of symptoms and a score of 0 being severely symptomatic. A 3-point difference was defined as clinically meaningful. A positive change from Baseline indicates improvement.

Change from Baseline was calculated using a used a mixed-model for repeated measures (MMRM) with treatment, stratification factors of residual disease, stage of disease, choice of paclitaxel dosing regimen and BRCA-deficient status, time point and treatment-by-time point interaction as fixed effect factors, and Baseline DRS score as a covariate.

DRS was not included in the fixed-sequence testing procedure.

Gynecologic Oncology Group;Australia New Zealand Gynaecological Oncology Group

AbbVie

Participants received placebo to veliparib orally twice a day in combination with carboplatin given at an area under the curve \[AUC\] of 6 mg per milliliter per minute (mg/mL/min), every 3 weeks, and paclitaxel 175 mg per square meter (mg/m²) of body-surface area (BSA), administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Placebo + Carboplatin + Paclitaxel -> Placebo

Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Veliparib + Carboplatin + Paclitaxel -> Placebo

Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received single-agent veliparib at a dose of 300 mg twice daily for 2 weeks (transition period) and then 400 mg veliparib twice daily if the dose in the transition period was not associated with limiting side effects for an additional thirty 21-day cycles of maintenance therapy.

Veliparib + Carboplatin + Paclitaxel -> Veliparib

Total

Age, Continuous

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

Geographic Region

The BRCA-mutation cohort was defined as participants who had deleterious or suspected deleterious germline (gBRCA) or tissue-based (tBRCA) mutations as determined by the Myriad BRACAnalysis® companion diagnostic (CDx) or myChoice® HRD CDx assay, respectively, in BRCA1 or BRCA2.

BRCA-Deficient Status

The HRD cohort consisted of participants who had tumors that were BRCA-mutated or had HRD according to the Myriad myChoice® assay, on which a score of ≥ 33 was considered to indicate HRD status, and a score of \< 33 was considered to indicate non-HRD status.

Homologous Recombination Deficiency (HRD) Status

Staging of primary ovarian carcinomas according to the International Federation of Gynecology and Obstetrics (FIGO) criteria, based on clinical examination, surgical exploration, histologic characteristics and cytologic testing.

STAGE III: Tumor involves 1 or both ovaries with cytologically or histologically confirmed spread to the peritoneum outside the pelvis and/or metastases to the retroperitoneal lymph nodes.

STAGE IV: Distant metastases excluding peritoneal metastases

Stage of Disease

Cytoreductive surgery could be performed before randomization and the initiation of study treatment (primary) or after 3 cycles of study treatment (interval), determined at the discretion of the investigator.

Type of Surgery Received

Data were collected after interval surgery after cycle 3.

Participants who underwent primary surgery

Residual Disease After Primary Surgery

Participants who underwent interval surgery

Residual Disease After Interval Surgery

Paclitaxel Dosing Regimen

Germline BRCA Status

The intention-to-treat (ITT) population consisted of all randomized participants.

Global Medical Services

The primary efficacy analyses compared investigator-assessed PFS in the Veliparib + Carboplatin + Paclitaxel -\> Veliparib group vs. the Placebo + Carboplatin + Paclitaxel -\> Placebo group.

Analyses were performed in 3 sequentially inclusive populations. The first analysis was conducted using the BRCA-mutation cohort which included participants with either a gBRCA and/or tBRCA deleterious or suspected deleterious mutation in BRCA1 or BRCA2.

Progression-Free Survival (PFS) in the BRCA-deficient Population

Analyses were performed in 3 sequentially inclusive populations. The second analysis was conducted using the HRD cohort which included participants in the BRCA-mutation cohort and those determined to have HRD tumors.

Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort

Analyses were performed in 3 sequentially inclusive populations. The third analysis was conducted using the intention-to-treat (ITT) population (all randomized participants).

Progression-Free Survival (PFS) in the Intention-to-treat Population

Overall Survival (OS)

Cycle 3

Cycle 5

Cycle 7

Cycle 9

Cycle 11

Cycle 13

Cycle 15

Cycle 17

Cycle 19

Cycle 21

Cycle 23

Cycle 25

Cycle 27

Cycle 29

Cycle 31

Cycle 33

Cycle 35

BRCA-mutation population, participants with available data at each time point.

Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population

HRD population, participants with available data at each time point.

Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population

ITT population, participants with available data at each time point.

Change From Baseline in Disease Related Symptom (DRS) Score in the ITT Population

Participants received placebo to veliparib orally twice a day in combination with carboplatin given at an area under the curve (AUC) of 6 milligrams per milliliter per minute (mg/mL/min) every 3 weeks, and paclitaxel 175 mg per square meter (mg/m²) of body-surface area (BSA), administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.

Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

Spots Global Cancer Trial Database for placebo to veliparib