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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: pemetrexed
* Drug: nivolumab
* Drug: paclitaxel
* Drug: veliparib
* Drug: carboplatin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Veliparib and nivolumab with platinum doublet chemotherapy<br>Veliparib and nivolumab in combination with platinum doublet chemotherapy (carboplatin/paclitaxel or carboplatin/pemetrexed) | Drug: pemetrexed<br>* intravenous; administered on Day 1 via infusion in a 21-day cycle<br>* Other names: Alimta;Drug: nivolumab<br>* intravenous; administered on Day 1 via infusion in a 21-day cycle<br>* Other names: Opdivo;Drug: paclitaxel<br>* intravenous; administered on Day 1 via infusion in a 21-day cycle<br>* Other names: Taxol;Drug: veliparib<br>* oral capsule; varying doses administered on Days -2 to 5 in a 21-day cycle<br>* Other names: ABT-888;Drug: carboplatin<br>* intravenous; administered on Day 1 via infusion in a 21-day cycle<br>* Other names: Paraplatin;|
| Experimental: Veliparib with platinum doublet chemotherapy<br>Veliparib in combination with platinum doublet chemotherapy (carboplatin/paclitaxel or carboplatin/pemetrexed) | Drug: pemetrexed<br>* intravenous; administered on Day 1 via infusion in a 21-day cycle<br>* Other names: Alimta;Drug: paclitaxel<br>* intravenous; administered on Day 1 via infusion in a 21-day cycle<br>* Other names: Taxol;Drug: veliparib<br>* oral capsule; varying doses administered on Days -2 to 5 in a 21-day cycle<br>* Other names: ABT-888;Drug: carboplatin<br>* intravenous; administered on Day 1 via infusion in a 21-day cycle<br>* Other names: Paraplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | 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. | Up to approximately 3.5 years | 
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax for pemetrexed |  | Up to approximately 3 weeks | 
| AUC for nivolumab |  | Up to approximately 3.5 years | 
| Overall Survival (OS) | 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. | Up to approximately 3.5 years | 
| Tmax for nivolumab |  | Up to approximately 3.5 years | 
| AUC for pemetrexed |  | Up to approximately 3 weeks | 
| Time to Cmax (peak time, Tmax) for veliparib |  | Up to approximately 9 weeks | 
| Area under the plasma concentration-time curve (AUC) for veliparib |  | Up to approximately 9 weeks | 
| Maximum observed serum concentration (Cmax) of nivolumab anti-drug antibody (ADA) |  | Up to approximately 3.5 years | 
| Duration of Overall Response (DOR) | 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. | Up to approximately 3.5 years | 
| Maximum observed plasma concentration (Cmax) for pemetrexed |  | Up to approximately 3 weeks | 
| Maximum observed plasma concentration (Cmax) for veliparib |  | Up to approximately 9 weeks | 
| Objective Response Rate (ORR) | ORR is defined as the proportion of the participants who have a complete response (CR) or partial response (PR). | Up to approximately 3.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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)