Ipilimumab and Nivolumab in Patients With Anti-PD-1-axis Therapy-resistant Advanced Non-small Cell Lung Cancer.

Description

The investigators propose a trial to evaluate if the addition of ipilimumab to nivolumab after primary resistance to anti- programmed death 1 (PD-1) axis therapy can lead to objective radiographic tumor regression.

Study Start Date

July, 20 2017

Estimated Completion Date

November 2020

Interventions

  • Biological: combination nivolumab and ipilimumab

Study ID

Yale University -- 2000020343

Status

Unknown

Trial ID

NCT03262779

Study Type

Interventional

Trial Phase

Phase 2

Enrollment Quota

50

Sponsor

Yale University

Inclusion Criteria

  • Histologically or cytologically documented, locally advanced or metastatic (i.e., Stage IIIB not eligible for definitive chemoradiotherapy, Stage IV, or recurrent) non-small cell lung cancer (NSCLC) (per the American Joint Committee /AJCC staging system)
  • Eastern Cooperative oncology Group (ECOG) performance status of 0 to 2.
  • Anti
  • programmed death (PD)-1 Axis therapy (anti-PD-1 or anti-PD-L1, e.g. nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab) must be the most recent systemic anti-tumor treatment received in all patients, with documented progressive disease: 1. Patients to be enrolled to the primary cohort (primary resistance) must have had progressive disease or stable disease less than 24 weeks as the best clinical response to anti-PD-1-axis therapy. 2. Patients to be enrolled to the exploratory cohort (acquired resistance) must have had stable disease for at least 24 weeks, partial response, or complete response as the best clinical response to anti-PD-1-axis therapy, with subsequent progression of disease.
  • Chemotherapy naive and treated patients will be eligible, with no limit on number of prior therapies. Patients with NSCLC known to harbor an ALK rearrangement, or EGFR mutation known to be sensitive to Food and Drug Administration (FDA) approved tyrosine kinase inhibitors (TKI), are only eligible after experiencing disease progression (during or after treatment) or intolerance to an FDA approved EGFR TKI or ALK TKI, respectively: 1. Patients with TKI treated EGFR mutant NSCLC harboring the secondary EGFR T790M tumor must have received prior osimertinib. 2. Patients with crizotinib treated ALK rearranged NSCLC must have received a next generation ALK inhibitor (e.g. ceritinib, alectinib or brigatinib).
  • At least one tumor amenable to incisional, excisional, core or forceps (transbronchial) biopsy. Patients must be willing to undergo tumor biopsies before starting trial therapy, and 9 to 10 weeks after initiation of therapy: 1. If the initial biopsy will be excisional, the excised tumor cannot be counted as a target lesion and there must be another lesion amenable to incisional, excisional, core or forceps biopsy. In this scenario, the second biopsy can only be excisional if the lesion to be excised is not a target lesion. 2. Cytology tumor specimens (e.g. from fine-needle biopsies, or drainage of pleural/ pericardial or ascites fluid) are not acceptable. Biopsies of bone lesions that do not have a soft tissue component are also not acceptable (i.e. decalcified tumor samples are not acceptable).
  • Adequate hematologic and end-organ function

Exclusion Criteria

  • Subjects must not have a history of life-threatening toxicity related to prior anti-PD-1 axis therapy: a. Subjects with history of anti-PD-1 axis therapy toxicities that are unlikely to recur with standard countermeasures (e.g., hormone replacement after adrenal crisis) are eligible.
  • Prior treatment with anti-cytotoxic T lymphocyte-associated molecule(CTLA)-4 therapeutic antibodies
  • Symptomatic or untreated central nervous system (CNS) metastases. Patients with a history of treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria: 1. No evidence of interim progression between the completion of CNS-directed therapy and the start of trial therapy.

Gender

All

Ages

18 Years and older

Accepts Healthy Volunteers

No

Study Locations and Contact Information (1)

Study Location Distance Name Phone Email
Yale Cancer Center - New Haven, Connecticut 18.2 miles Heather Findley 203-823-0219 Heather.Findley@yale.edu

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