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Study of Veliparib in Combination With Nivolumab and Platinum Doublet Chemotherapy in Participants With Metastatic or Advanced Non-Small Cell Lung Cancer (NSCLC)

Phase 1
Completed
Conditions
Non-Small Cell Lung Cancer
Interventions
Registration Number
NCT02944396
Lead Sponsor
AbbVie
Brief Summary

This study seeks to establish the recommended Phase 2 dose (RPTD) of veliparib in combination with nivolumab and platinum doublet chemotherapy (carboplatin/paclitaxel or carboplatin/pemetrexed) (Phase 1 portion) and to assess whether the addition of nivolumab to veliparib in combination with platinum doublet chemotherapy results will improve progression free survival (PFS) compared to veliparib with platinum doublet chemotherapy alone in participants with metastatic or advanced Non-small Cell Lung Cancer (NSCLC) (Phase 2 portion).

A strategy decision was made not to proceed to Phase 2 portion of this study due to change in standard of care.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
25
Inclusion Criteria
  • Participant must have a life expectancy greater than 12 weeks,
  • Participant must have cytologically or histologically confirmed Non-small Cell Lung Cancer (NSCLC).
  • Participant must have metastatic or advanced NSCLC (Stage IIIB or IV) that is not amenable to surgical resection or radiation or chemoradiation with curative intent at time of study screening.
  • Participant 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).
  • Participant must have resolution to Grade 1 or lower of any toxic effects (excepting alopecia) of the most recent therapy prior to Cycle 1 Day 2.
  • Participant must have an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 to 1.
  • Participant must have adequate bone marrow, renal, and hepatic function.
Exclusion Criteria
  • Participant has received prior cytotoxic chemotherapy (including chemotherapy in combination with radiotherapy) for NSCLC, except for adjuvant or neoadjuvant therapy accompanied by surgery with curative intent that was completed one year prior to Cycle 1 Day -2.
  • Participant has received prior therapy with a Poly-(ADP-ribose)-Polymerase (PARP) inhibitor.
  • Participant has received prior treatment with any anti-programmed cell death protein-1 (anti-PD-1), or PD Ligand-1 (PD-L1) or PD Ligand-2 (PD-L2) agent or an antibody targeting other immunoregulatory receptors or mechanisms.
  • Participant has received radiation therapy to lung greater than 30 Gy within 6 months, or antineoplastic biologic therapy within 21 days, or major surgery within 21 days, or tyrosine kinase inhibitor therapy within 7 days, or palliative radiation within 7 days of the first dose of study medication.
  • Participant has untreated central nervous system (CNS) metastases.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Veliparib and nivolumab with platinum doublet chemotherapypemetrexedVeliparib and nivolumab in combination with platinum doublet chemotherapy (carboplatin/paclitaxel or carboplatin/pemetrexed)
Veliparib and nivolumab with platinum doublet chemotherapypaclitaxelVeliparib and nivolumab in combination with platinum doublet chemotherapy (carboplatin/paclitaxel or carboplatin/pemetrexed)
Veliparib with platinum doublet chemotherapypemetrexedVeliparib in combination with platinum doublet chemotherapy (carboplatin/paclitaxel or carboplatin/pemetrexed)
Veliparib and nivolumab with platinum doublet chemotherapynivolumabVeliparib and nivolumab in combination with platinum doublet chemotherapy (carboplatin/paclitaxel or carboplatin/pemetrexed)
Veliparib and nivolumab with platinum doublet chemotherapycarboplatinVeliparib and nivolumab in combination with platinum doublet chemotherapy (carboplatin/paclitaxel or carboplatin/pemetrexed)
Veliparib and nivolumab with platinum doublet chemotherapyveliparibVeliparib and nivolumab in combination with platinum doublet chemotherapy (carboplatin/paclitaxel or carboplatin/pemetrexed)
Veliparib with platinum doublet chemotherapypaclitaxelVeliparib in combination with platinum doublet chemotherapy (carboplatin/paclitaxel or carboplatin/pemetrexed)
Veliparib with platinum doublet chemotherapyveliparibVeliparib in combination with platinum doublet chemotherapy (carboplatin/paclitaxel or carboplatin/pemetrexed)
Veliparib with platinum doublet chemotherapycarboplatinVeliparib in combination with platinum doublet chemotherapy (carboplatin/paclitaxel or carboplatin/pemetrexed)
Primary Outcome Measures
NameTimeMethod
Progression-free survival (PFS)Up to approximately 3.5 years

PFS is defined as the number of days from the date of randomization to the date of earliest disease progression (radiographic progression per RECIST version 1.1 or clinical disease progression) or death. If the participant does not experience disease progression or death, then the data will be censored at the date of the last disease assessment.

Recommended Phase 2 dose (RPTD) of veliparib (ABT-888) in combination with nivolumab and platinum doublet chemotherapy in participants with metastatic or advanced Non-Small Cell Lung Cancer (NSCLC).Up to 6 weeks
Secondary Outcome Measures
NameTimeMethod
Maximum observed plasma concentration (Cmax) for veliparibUp to approximately 9 weeks
AUC for nivolumabUp to approximately 3.5 years
Tmax for nivolumabUp to approximately 3.5 years
Time to Cmax (peak time, Tmax) for veliparibUp to approximately 9 weeks
Objective Response Rate (ORR)Up to approximately 3.5 years

ORR is defined as the proportion of the participants who have a complete response (CR) or partial response (PR).

Overall Survival (OS)Up to approximately 3.5 years

OS is defined as the number of days from the date of randomization to the date of death. For subjects who did not die, their data will be censored at the date of last study visit or the last known date to be alive, whichever is later.

Duration of Overall Response (DOR)Up to approximately 3.5 years

DOR is defined as the number of days from the date of first response (CR or PR) to the earliest documentation of progressive disease or death due to disease progression.

Maximum observed plasma concentration (Cmax) for pemetrexedUp to approximately 3 weeks
Tmax for pemetrexedUp to approximately 3 weeks
Area under the plasma concentration-time curve (AUC) for veliparibUp to approximately 9 weeks
AUC for pemetrexedUp to approximately 3 weeks
Maximum observed serum concentration (Cmax) of nivolumab anti-drug antibody (ADA)Up to approximately 3.5 years

Trial Locations

Locations (6)

University of Chicago /ID# 153824

🇺🇸

Chicago, Illinois, United States

Duke University Medical Center /ID# 153821

🇺🇸

Durham, North Carolina, United States

University of Alabama at Birmingham - Main /ID# 155135

🇺🇸

Birmingham, Alabama, United States

Goshen Center for Cancer Care /ID# 153822

🇺🇸

Goshen, Indiana, United States

Icri /Id# 155593

🇺🇸

Whittier, California, United States

Univ of Colorado Cancer Center /ID# 153820

🇺🇸

Aurora, Colorado, United States

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