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

Non-Small Cell Lung Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02944396
• Other study ID #: M15-534
• Secondary ID: 2016-001658-16
• Status: Completed
• Phase: Phase 1
• Start date: December 23, 2016
• Est. completion date: October 2, 2019

Study information

• Verified date: October 2019
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: October 2, 2019
• Est. primary completion date: October 2, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• pemetrexed
intravenous; administered on Day 1 via infusion in a 21-day cycle
• nivolumab
intravenous; administered on Day 1 via infusion in a 21-day cycle
• paclitaxel
intravenous; administered on Day 1 via infusion in a 21-day cycle
• veliparib
oral capsule; varying doses administered on Days -2 to 5 in a 21-day cycle
• carboplatin
intravenous; administered on Day 1 via infusion in a 21-day cycle

Locations

Country	Name	City	State
United States	Univ of Colorado Cancer Center /ID# 153820	Aurora	Colorado
United States	University of Alabama at Birmingham - Main /ID# 155135	Birmingham	Alabama
United States	University of Chicago /ID# 153824	Chicago	Illinois
United States	Duke University Medical Center /ID# 153821	Durham	North Carolina
United States	Goshen Center for Cancer Care /ID# 153822	Goshen	Indiana
United States	Icri /Id# 155593	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Tmax for pemetrexed		Up to approximately 3 weeks
Secondary	AUC for nivolumab		Up to approximately 3.5 years
Secondary	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
Secondary	Tmax for nivolumab		Up to approximately 3.5 years
Secondary	AUC for pemetrexed		Up to approximately 3 weeks
Secondary	Time to Cmax (peak time, Tmax) for veliparib		Up to approximately 9 weeks
Secondary	Area under the plasma concentration-time curve (AUC) for veliparib		Up to approximately 9 weeks
Secondary	Maximum observed serum concentration (Cmax) of nivolumab anti-drug antibody (ADA)		Up to approximately 3.5 years
Secondary	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
Secondary	Maximum observed plasma concentration (Cmax) for pemetrexed		Up to approximately 3 weeks
Secondary	Maximum observed plasma concentration (Cmax) for veliparib		Up to approximately 9 weeks
Secondary	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