Last updated on July 2019

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)

Are you eligible to participate in this study?

You may be eligible for this study if you meet the following criteria:

  • Conditions: Non-Small Cell Lung Cancer
  • Age: 18 Years
  • Gender: Male or Female

Main Inclusion:

  1. Subject must be ≥ 18 years of age.
  2. Life expectancy > 12 weeks (as per Investigator's clinical assessment).
  3. Subject must have cytologically or histologically confirmed NSCLC.
  4. Subject 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. Subjects with such NSCLC that is recurrent after surgical treatment are eligible.
  5. Subject must have at least 1 unidimensional measurable NSCLC lesion on a CT scan as defined by RECIST (version 1.1).
  6. Subject must consent to provide available archived core biopsy or surgical tissue sample of NSCLC lesion (primary or metastatic) for central review and biomarker analysis. Archival tissue will be tested to determine stratification prior to subject randomization (Phase 2 ONLY). If no archival tissue is available, core biopsy during screening for PD-L1 testing is required.
  7. Subject 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.
  8. Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 to 1.
  9. Subject must be able to take oral medication (PO).
  10. Subject must have adequate bone marrow, renal and hepatic function as follows:
    • Bone Marrow: Absolute neutrophil count (ANC) ≥ 1500/mm3 (1.5 × 109/L); Platelets = 100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL (5.59 mmol/L);
    • Renal function: calculated creatinine clearance > 50 mL/min/1.73 m2 according the Cockcroft- Gault formula;
    • Hepatic function: AST and ALT = 2.5 × ULN unless liver metastases are present, then AST and ALT < 5.0 × ULN; bilirubin ≤ 1.5 × ULN; or subjects with Gilbert's Syndrome may have a bilirubin ≥ 1.5 × ULN of central laboratory normal range.
  11. Subject must be capable of understanding and complying with parameters as outlined in the protocol, and must voluntarily sign and date each informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB) prior to the initiation of any screening or study specific procedures.
  12. If female, subject must be either postmenopausal, OR permanently surgically sterile OR for Women of Childbearing Potential practicing at least one protocol specified method of birth control, starting from treatment initiation through at least 6 months after the last dose of veliparib or nivolumab. If the male subject is sexually active with female partner(s) of childbearing potential, he must agree, starting from treatment initiation through 8 months after the last dose of veliparib or nivolumab, to practice the protocol specified contraception.
Main Exclusion:
  1. Subject 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.
  2. Subject has received prior therapy with a Poly-(ADP-ribose)-Polymerase (PARP) inhibitor.
  3. Subject 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.
  4. Subject has received radiation therapy to lung > 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.
  5. Subject is currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of Cycle 1 Day –2.
  6. Subjects with untreated central nervous system (CNS) metastases are excluded. Subjects are eligible if treatment for CNS metastases has been completed for at least 2 weeks prior to Cycle 1 Day –2, subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment), and subjects are not receiving corticosteroid treatment for CNS disease.
  7. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  8. Subject has active or history of interstitial lung disease or pneumonitis
  9. Subject is receiving chronic systemic steroid therapy or on any other form of immunosuppressive medication. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
  10. Subject has received a live-virus vaccination within 30 days of planned treatment start.
  11. Subject has peripheral neuropathy ≥ Grade 2.
  12. Subject has active infection of Human Immunodeficiency Virus (HIV), Hepatitis B or C requiring therapy.
  13. Subject has history of uncontrolled seizure disorder, or has had a focal or generalized seizure within the past year.
  14. Subject has history of severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb) or study chemotherapy agents.
  15. History of a hematologic malignancy or invasive primary solid malignancy, unless the subject has undergone potentially curative therapy with no evidence of that disease for 3 years.
  16. Any medical condition, which in the opinion of the Investigator, places the subject at an unacceptably high risk for toxicities, or any subject circumstance that prohibits trial participation according to local law.
  17. Female subject who is pregnant, breastfeeding or is considering becoming pregnant during the study or for approximately 6 months after the last dose of veliparib or nivolumab; or male subject who is considering fathering a child or donating sperm during the study or for approximately 6 months after the last dose of veliparib or nivolumab.

Recruitment Status: Open

Brief Description Eligibility Contact Research Team

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