Clinical trial NCT02944396: Study of Veliparib in Combination With Nivolumab and Platinum Doublet Chemotherapy in Participants With Metastatic or Advanced Non-Small Cell Lung Cancer (NSCLC)
Official title: A Phase 1 Dose-Escalation and Phase 2 Randomized, Open-Label Study of Nivolumab and Veliparib in Combination With Platinum Doublet Chemotherapy in Subjects With Metastatic or Advanced Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Keywords: metastatic
non-small cell lung cancer
Eastern Cooperative Oncology Group (ECOG)
veliparib
nivolumab
Platinum Doublet Chemotherapy
carboplatin
paclitaxel
pemetrexed
Response Evaluation Criteria In Solid Tumors (RECIST)
Common Terminology Criteria for Adverse Events (CTCAE)
Poly (ADP) ribose polymerase (PARP)
Immuno Oncology
Metastatic or Advanced Non-Small Cell Lung Cancer (NSCLC)
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2016-10-25
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 3.5 years
measure: 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).
timeFrame: Up to 6 weeks
Secondary outcomes:
measure: Tmax for pemetrexed
timeFrame: Up to approximately 3 weeks
measure: AUC for nivolumab
timeFrame: Up to approximately 3.5 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 3.5 years
measure: Tmax for nivolumab
timeFrame: Up to approximately 3.5 years
measure: AUC for pemetrexed
timeFrame: Up to approximately 3 weeks
measure: Time to Cmax (peak time, Tmax) for veliparib
timeFrame: Up to approximately 9 weeks
measure: Area under the plasma concentration-time curve (AUC) for veliparib
timeFrame: Up to approximately 9 weeks
measure: Maximum observed serum concentration (Cmax) of nivolumab anti-drug antibody (ADA)
timeFrame: Up to approximately 3.5 years
measure: Duration of Overall Response (DOR)
timeFrame: Up to approximately 3.5 years
measure: Maximum observed plasma concentration (Cmax) for pemetrexed
timeFrame: Up to approximately 3 weeks
measure: Maximum observed plasma concentration (Cmax) for veliparib
timeFrame: Up to approximately 9 weeks
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 3.5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham - Main /ID# 155135
state: Alabama
city: Whittier
country: United States
facility: Icri /Id# 155593
state: California
city: Aurora
country: United States
facility: Univ of Colorado Cancer Center /ID# 153820
state: Colorado
city: Chicago
country: United States
facility: University of Chicago /ID# 153824
state: Illinois
city: Goshen
country: United States
facility: Goshen Center for Cancer Care /ID# 153822
state: Indiana
city: Durham
country: United States
facility: Duke University Medical Center /ID# 153821
state: North Carolina
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References: