Study Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Adults Receiving First Cytotoxic Chemotherapy for Metastatic or Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC) and Who Are Current or Former Smokers

• ClinicalTrials.gov Identifier: NCT02264990
• Recruitment Status: Completed
• First Posted: October 15, 2014
• Results First Posted: February 26, 2021
• Last Update Posted: February 26, 2021
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: October 9, 2014
• First Posted Date: October 15, 2014
• Results First Submitted Date: February 8, 2021
• Results First Posted Date: February 26, 2021
• Last Update Posted Date: February 26, 2021
• Actual Study Start Date: September 30, 2014
• Actual Primary Completion Date: November 14, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 8, 2021)

Overall Survival (OS) in the Lung Subtype Panel Positive Subgroup [ Time Frame: From randomization up to the data cut-off date of 15 July 2019; median follow-up time was 44.5 and 45.3 months in LSP+ participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively. ]

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.

Original Primary Outcome Measures (submitted: October 9, 2014)

Overall Survival (OS) in current smokers [ Time Frame: Up to 3 years from first dose of study drug. ]

Overall survival is defined as the number of days from the date that the participant was randomized to the date of the participant's death.

Current Secondary Outcome Measures (submitted: February 8, 2021)

• Progression Free Survival (PFS) in the Lung Subtype Panel Positive Subgroup [ Time Frame: From randomization up to the data cut-off date of 15 July 2019; the median follow-up time was 44.5 and 45.3 months in LSP+ participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively. ]
  Progression-free survival is defined as the time from the date of randomization to the date of disease progression (PD) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or death (all causes of mortality), whichever occurred first. PD: At least a 20% increase in the size of target lesions, taking as reference the smallest size recorded since the treatment started (Baseline or after) with an absolute increase of at least 5 mm, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. PFS was estimated using Kaplan-Meier methodology. Participants who did not have an event of disease progression or had not died on or before the cutoff date were censored at the date of their last disease progression assessment on or before the cut-off date. Any PD and death occurring > 26 weeks and > 12 weeks after the previous assessment, respectively, were excluded and patients were censored at last assessment before PD or death.
• Objective Response Rate (ORR) in the Lung Subtype Panel Positive Subgroup [ Time Frame: Assessed on Day 1 of Cycles 3 and 5 then every 9 weeks for 1 year or until maintenance therapy was discontinued, then every 12 weeks until radiographic progression or death; median time on follow-up was 5.2 and 6.3 months in each group, respectively. ]
  Objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria. Response must have been confirmed at a consecutive assessment 28 days or more after the assessment at which response was first observed. CR: The disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters, persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, or any new lesions.
• Overall Survival in All Participants [ Time Frame: From randomization up to the data cut-off date of 15 July 2019; the median OS follow-up time was 45.4 and 44.6 months in all participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively. ]
  Overall survival is defined as the time from the date that the participant was randomized to the date of the participant's death. OS 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.
• Progression Free Survival (PFS) in All Participants [ Time Frame: From randomization up to the data cut-off date of 15 July 2019; the median follow-up time was 45.4 and 44.6 months in all participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively. ]
  Progression-free survival is defined as the time from the date of randomization to the date of disease progression (PD) per RECIST version 1.1 or death (all causes of mortality), whichever occurred first. PD: At least a 20% increase in the size of target lesions, taking as reference the smallest size recorded since the treatment started (Baseline or after) with an absolute increase of at least 5 mm, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. PFS was estimated using Kaplan-Meier methodology. Participants who did not have an event of disease progression or had not died on or before the cut-off date were censored at the date of their last disease progression assessment on or before the cut-off date. Any PD and death occurring > 26 weeks and > 12 weeks after the previous assessment, respectively, were excluded and patients were censored at last assessment before PD or death.
• Objective Response Rate (ORR) in All Participants [ Time Frame: Assessed on Day 1 of Cycles 3 and 5 then every 9 weeks for 1 year or until maintenance therapy was discontinued, then every 12 weeks until radiographic progression or death; median time on follow-up was 6.7 and 5.9 months in each group, respectively. ]
  Objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) per RECIST version 1.1 criteria. Response must have been confirmed at a consecutive assessment 28 days or more after the assessment at which response was first observed. CR: The disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters, persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, or any new lesions.

Original Secondary Outcome Measures (submitted: October 9, 2014)

• Overall Survival (OS) in all participants [ Time Frame: Up to 5 years from first dose of study drug. ]
  Overall survival is defined as the number of days from the date that the participant was randomized to the date of the participant's death.
• Progression Free Survival (PFS) in current smokers and all participants [ Time Frame: Up to 5 years from first dose of study drug ]
  Progression-free survival is defined as the number of days from participant randomization to the date the participant experiences an event of disease progression (PD) or death (all causes of mortality), if PD is not reached.
• Objective Response Rate (ORR) in current smokers and all participants [ Time Frame: Up to 3 years from first dose of study drug ]
  Objective response rate is defined as the proportion of participants with complete or partial response as determined by the investigator per Response Evaluation Criteria In Solid Tumors (version 1.1).

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: October 9, 2014)

• Duration of overall response (DOR) in current smokers and in all participants [ Time Frame: Up to 3 years from randomization. ]
  The duration of overall response for a participant is defined as the number of days from when the criteria is met for a complete or partial response (whichever occurs first), to the date that progressive disease (PD) is objectively documented.
• Change in Eastern Cooperative Oncology Group (ECOG) Performance Status in current smokers and in all participants [ Time Frame: From Screening (prior to dosing) up to 2 years ]
• Change in Quality of Life in current smokers and in all participants [ Time Frame: From Screening (prior to dosing) up to 2 years ]
  Participants will answer the European Quality of Life-5 Dimensions-5 Levels Questionnaire (EQ-5D-5L) and the Functional Assessment of Cancer Therapy (FACT) Lung Symptom Index-17 questionnaire.

Descriptive Information

• Brief Title: Study Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Adults Receiving First Cytotoxic Chemotherapy for Metastatic or Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC) and Who Are Current or Former Smokers
• Official Title: A Randomized, Open-Label, Multicenter, Phase 3 Trial Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Subjects Receiving First Cytotoxic Chemotherapy for Metastatic or Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC) and Who Are Current or Former Smokers
• Brief Summary: The purpose of this study is to evaluate the safety and efficacy of veliparib plus carboplatin and paclitaxel versus the Investigator's choice of standard chemotherapy in adults with metastatic or advanced non-squamous non-small cell lung cancer.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-squamous Non-small Cell Lung Cancer

Intervention

• Drug: Paclitaxel
  Administered by Intravenous infusion on Day 1 of each 21-day cycle
• Drug: Carboplatin
  Administered by Intravenous infusion on Day 1 of each 21-day cycle
• Drug: Cisplatin
  Administered by Intravenous infusion on Day 1 of each 21-day cycle
• Drug: Veliparib
  Oral capsule, administered twice daily for 7 days in each 21-day cycle
  Other Name: ABT-888
• Drug: Pemetrexed
  Administered by Intravenous infusion on Day 1 of each 21-day cycle
  Other Name: Alimta

Study Arms

• Experimental: Veliparib + Carboplatin + Paclitaxel

  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.

  Interventions:

  • Drug: Paclitaxel
  • Drug: Carboplatin
  • Drug: Veliparib
  • Drug: Pemetrexed
• Active Comparator: Investigator's Choice Chemotherapy

  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.

  Interventions:

  • Drug: Paclitaxel
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Pemetrexed

• Publications *: Govindan R, Lind M, Insa A, Khan SA, Uskov D, Tafreshi A, Guclu S, Bar J, Kato T, Lee KH, Nakagawa K, Hansen O, Biesma B, Kundu MG, Dunbar M, He L, Ansell P, Sehgal V, Huang X, Glasgow J, Bach BA. Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer. Clin Lung Cancer. 2022 May;23(3):214-225. doi: 10.1016/j.cllc.2022.01.005. Epub 2022 Feb 4.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 23, 2018): 595
• Original Estimated Enrollment (submitted: October 9, 2014): 525
• Actual Study Completion Date: February 21, 2020
• Actual Primary Completion Date: November 14, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 or radiation with curative intent at time of screening.
• Subject must have at least 1 unidimensional measurable NSCLC lesion on a computed tomography (CT) scan as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Exclusion Criteria:

• Subject has a known hypersensitivity to paclitaxel or to other drugs formulated with polyethoxylated castor oil (Cremophor).
• Subject has a known hypersensitivity to platinum compounds.
• Subject has peripheral neuropathy ≥ grade 2.
• Subject has squamous NSCLC, or an untreated known epidermal growth factor receptor (EGFR) mutation of exon 19 deletion or L858R mutation in exon 21, or a known anaplastic lymphoma kinase (ALK) gene rearrangement.
• Subject has received prior cytotoxic chemotherapy or chemoradiotherapy for NSCLC.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Canada, Czechia, Denmark, Finland, Germany, Hungary, Israel, Japan, Korea, Republic of, Netherlands, New Zealand, Russian Federation, South Africa, Spain, Taiwan, Turkey, United Kingdom, United States
• Removed Location Countries: Czech Republic, France

Administrative Information

• NCT Number: NCT02264990
• Other Study ID Numbers: M14-359; 2014-002565-30 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: AbbVie Inc.; AbbVie

• PRS Account: AbbVie
• Verification Date: February 2021