OUTLINE: This is a multi-center study.
Eligible subjects will be randomized in 1:1 ratio to receive treatment with either:
Arm A: docetaxel 75 mg/meters squared (mg/m2) plus nivolumab 360 mg IV every 21 days
Arm B: docetaxel alone 75 mg/m2 every 21 days
For both treatment arms, 21 days equals 1 cycle of therapy and subjects will be eligible to continue treatment until progressive disease by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) or unacceptable toxicity.
The following screening labs to demonstrate adequate organ function must be performed within 30 days prior to registration:
- White Blood Cell (WBC) ≥ 2 k/mm3
- Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm3
- Platelets >100k
- Hemoglobin ≥ 9 g/dL
- Calculated creatinine clearance ≥ 40 cc/min
- Bilirubin 1.5 ≤ upper limit of normal (ULN)
- Aspartate aminotransferase (AST) ≤ 1.5 × ULN
- Alanine aminotransferase (ALT) ≤ 1.5 × ULN
- International Normalized Ratio (INR) or Prothrombin Time (PT) or Activated Partial Thromboplastin Time (aPTT) ≤ 2 × ULN
(Note: use of vitamin K antagonist is not allowed)
Subject must meet all of the following applicable inclusion criteria to participate in this study:
- Written informed consent and the American Health Insurance Portability and Accountability Act of 1996 (HIPAA) authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- Age ≥ 18 years at the time of consent.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 within 30 days prior to registration.
- Histological or cytological confirmed non-squamous non-small cell lung cancer.
- Measurable disease according to RECIST 1.1 within 30 days prior to registration.
- A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to study registration, have been off of corticosteroids for ≥ 2 weeks, and are asymptomatic.
- Subjects must have had clinical benefit while on single agent nivolumab defined as at least a 3 month PFS, and now have progression.
- Most recent therapy must have been treatment with single agent Nivolumab. Subjects must have experienced disease progression during or after single agent Nivolumab therapy.
- Most recent Nivolumab infusion must be completed at least 6 weeks of randomization. The subject must have recovered from all reversible acute toxic effects (other than alopecia) to ≤ Grade 1 or baseline.
- MANDATORY archival tumor tissue (prior to treatment with single agent Nivolumab) must be identified prior to registration and obtained during the screening period. Confirmation of acquisition should occur prior to C1D1 treatment. Unavailability of tissue will render the subject ineligible for study. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient. Sample requirement is FFPE block + 1 H&E stained slide or 25 unstained slides + 1 H&E stained slide.
- MANDATORY biopsy after registration and prior to C1D1 treatment: Primary tumor or a metastatic lesion must be amenable to biopsy after registration and prior to C1D1 treatment for PD-L1 status and other correlative studies. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient.
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 14 days prior to registration. These women must also have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of Nivolumab then every 6 weeks thereafter. NOTE: Women are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is post-menopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 62 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL.
- Women of childbearing potential must be willing to abstain from heterosexual activity or use 2 forms of effective methods of contraception from the time of informed consent until 5 months after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method. Women cannot breast feed from the time of informed consent to 5 months after last dose of study treatment.
- Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving Nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product.
- As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
Subjects meeting any of the criteria below may not participate in the study:
- Prior treatment with docetaxel.
- Previous autoimmune complication from nivolumab requiring discontinuation of therapy or treatment with steroids (ongoing treatment with more than 10 mg of prednisone or steroid equivalent daily, excluding inhaled or topical steroids).
- Previous discontinuation from Nivolumab due to an adverse event.
- Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L-2, anti-CD-137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). Exception: nivolumab.
- Any serious or uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy.
- Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
- Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
- Active central nervous system (CNS) metastases. Subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for [lowest minimum is 4 weeks or more] after treatment is complete and within 28 days prior to the first dose of nivolumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
- Treatment with any investigational drug within 30 days prior to registration.
- Subjects whose tumors express EGFR mutations on exons 19 and 21, ALK rearrangement, or ROS1 rearrangement who still have other FDA approved targeted agents available for treatment.
- Subjects with an active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids/immunosuppressive medications EXCEPT for syndromes which would not be expected to recur in the absence of an external trigger. (Subjects with vitiligo, autoimmune thyroiditis, or type I diabetes mellitus are permitted to enroll.)
- As there is potential for hepatic toxicity with nivolumab, drugs with a predisposition to hepatoxicity should be used with caution in subjects treated with nivolumab-containing regimen.
- Subjects should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
- Subjects should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
- History of allergy to study drug components.
|Maximum Eligible Age:||N/A|
|Minimum Eligible Age:||18 Years|