Clinical Trial 18909

Cancer Type: Thoracic
Interventions:BMS-936558 (Nivolumab); Nivolumab; Not Applicable

Study Type: Treatment
Phase of Study: Phase III
Investigators:

  • Jhanelle Gray

Overview

Study Title

Adjuvant Nivolumab in Resected Lung Cancers (ANVIL) A Randomized Phase III Study of Nivolumab After Surgical Resection and Adjuvant Chemotherapy in Non-Small Cell Lung Cancers

Summary

This randomized phase III trial studies how well nivolumab after surgery and chemotherapy work in treating patients with stage IB-IIIA non-small cell lung cancer. Monoclonal antibodies, such as nivolumab, may stimulate the immune system in different ways and kill tumor cells remaining after surgery and standard of care chemotherapy.

Objective

2.1 Co-Primary Endpoints: 2.1.1 To evaluate whether adjuvant therapy with nivolumab will result in improved overall survival (OS) and/or disease-free survival (DFS) over standard observation in patients with Stage IB.4cm, II and IIIA, NSCLC following surgical resection and standard adjuvant therapy. 2.2 Secondary Endpoints: 2.2.1 To evaluate the safety profile of nivolumab when given as an adjuvant therapy. 2.2.2 To evaluate and compare disease free and overall survival in patients with tumors that express PD-L1 in various patterns associated with nivolumab and standard observation. 2.2.3 To evaluate and compare disease free and overall survival in patients with tumors that have high mutational load associated with nivolumab and standard observation. 2.2.4 To evaluate OS and DFS by stage. 2.2.5 To evaluate OS and DFS by each stratification factor. 2.2.6 To evaluate the proportion of patients alive and progression free at 1 year, 2 years, and 5 years (OS and DFS rate).

Inclusion Criteria

  • Age 18 years or older
  • Must have undergone complete surgical resection of their stage IB (>= 4 cm), II or IIIA NSCLC according to the American Joint Committee on Cancer (AJCC) 7th edition and have had negative surgical margins
  • Baseline chest computed tomography (CT) must be performed within 1 month (30 days) of randomization to ensure no evidence of disease; if clinically indicated, additional imaging studies must be performed to rule out metastatic disease
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Must be registered to the ALCHEMIST-SCREEN (ALLIANCE A151216) trial prior to randomization
  • Non-squamous tumors must be epidermal growth factor receptor (EGFR) and anaplastic lymphoma receptor tyrosine kinase (ALK) wild-type (results ascertained in centrally as part of ALCHEMIST-SCREEN protocol)
  • Tumors must have PD-L1 status tested centrally as part of the ALCHEMIST-SCREEN protocol
  • Women must not be pregnant or breast-feeding
  • Must not have uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements
  • No prior treatment with an immune checkpoint inhibitor (anti-programmed cell death [PD]-1, anti-PD-L1, anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA4] monoclonal antibody)
  • Must have adequately recovered from surgery and chemotherapy at the time of randomization
  • Must have completed and recovered from any adjuvant chemotherapy 2 or more weeks prior to randomization (6 weeks for mitomycin and nitrosoureas; 4 weeks for post-operative radiation therapy)
  • Adequate organ and marrow function
  • Prior to randomization patients with any non-hematologic toxicity from surgery, chemotherapy and radiation therapy must have recovered to grade less than or equal to 1 with the exception of alopecia, ototoxicity and neuropathy
  • Must not be receiving any other investigational anti-cancer agents while on study
  • Must not have known or suspected autoimmune disease; potential participants with type I diabetes mellitus, hypothyroidism requiring hormone replacement, or skin disorders not requiring systemic treatment are permitted to enroll.

  • Exclusion Criteria

  • Have a condition requiring systemic corticosteroids equivalent to > 10 mg prednisone per day or other immunosuppressive medications within 2 weeks of randomization
  • Have known interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
  • Have a known history of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection that is untreated and/or with a detectable viral load
  • Have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab