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

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)

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.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: pemetrexed; Drug: nivolumab; Drug: paclitaxel; Drug: veliparib; Drug: carboplatin

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham - Main /ID# 155135
  • California
    • Whittier, California, United States, 90603
      • Icri /Id# 155593
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Univ of Colorado Cancer Center /ID# 153820
  • Illinois
    • Chicago, Illinois, United States, 60637-1443
      • University of Chicago /ID# 153824
  • Indiana
    • Goshen, Indiana, United States, 46526
      • Goshen Center for Cancer Care /ID# 153822
  • North Carolina
    • Durham, North Carolina, United States, 27710-3000
      • Duke University Medical Center /ID# 153821

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2016
• Primary Completion (Actual): October 2, 2019
• Study Completion (Actual): October 2, 2019

Study Registration Dates

• First Submitted: October 19, 2016
• First Submitted That Met QC Criteria: October 24, 2016
• First Posted (Estimate): October 25, 2016

Study Record Updates

• Last Update Posted (Actual): October 23, 2019
• Last Update Submitted That Met QC Criteria: October 21, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: veliparib; non-small cell lung cancer; paclitaxel; carboplatin; metastatic; nivolumab; pemetrexed; Eastern Cooperative Oncology Group (ECOG); Common Terminology Criteria for Adverse Events (CTCAE); Platinum Doublet Chemotherapy; Response Evaluation Criteria In Solid Tumors (RECIST); Poly (ADP) ribose polymerase (PARP); Immuno Oncology; Metastatic or Advanced Non-Small Cell Lung Cancer (NSCLC)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Poly(ADP-ribose) Polymerase Inhibitors; Immune Checkpoint Inhibitors; Folic Acid Antagonists; Carboplatin; Paclitaxel; Nivolumab; Veliparib; Pemetrexed
• Other Study ID Numbers: M15-534; 2016-001658-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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