138TiP - An open-label phase 3b/4 safety trial of flat-dose nivolumab plus ipilimumab in patients with advanced non-small cell lung cancer (NSCLC)

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Immunotherapy
Thoracic malignancies
Non-small-cell lung cancer
Presenter Luis Paz-Ares
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors L. Paz-Ares1, B. Lash2, I. Albert3, G. Gagnon4, C. Chakmakjian5, N. Ready6, W. Hu7, L. Krug7, J. Fairchild7, R.N. Pillai8
  • 1Hospital Universitario Doce de Octubre, 28041 - Madrid/ES
  • 2Guthrie Medical Group, 18840 - Sayre/US
  • 3Matrai Gyogyintezet, 3233 - Matrahaza/HU
  • 4CISSS du Bas-Saint-Laurent Hopital Regional de Rimouski, G5L 5T1 - Rimouski/CA
  • 5Texas Oncology Cancer Care and Research Center, 76712 - Waco/US
  • 6Duke University, 27710 - Durham/US
  • 7Bristol-Myers Squibb, 08648 - Princeton/US
  • 8Winship Cancer Institute, Emory University, Atlanta/US



The combination of nivolumab and ipilimumab, immune checkpoint inhibitors with distinct but complementary mechanisms of action, is approved as first-line therapy for metastatic melanoma and has shown encouraging clinical activity in other tumors, including NSCLC. In CheckMate 012, a multi-cohort phase 1 trial in chemotherapy-naïve patients with NSCLC, nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) yielded objective response rates of up to 47%; discontinuation rates due to treatment-related adverse events were similar to those with nivolumab monotherapy. Data indicate comparable pharmacokinetic, safety, and efficacy profiles for 240 mg flat-dose nivolumab and 3 mg/kg nivolumab. This open-label phase 3b/4 study (ClinicalTrials.gov identifier: NCT02869789) will characterize the safety of flat-dose nivolumab plus ipilimumab in patients with advanced NSCLC. This study will also evaluate this combination in special patient populations who are typically excluded from NSCLC trials.

Trial design

Adult patients with stage IV/recurrent NSCLC and no prior systemic anticancer therapy (cohort A; n = 400), or with stage IIIb/IV NSCLC and recurrence or progression during or after one prior platinum doublet chemotherapy regimen (cohort B; n = 400) will be enrolled. Patients are required to have assessment of programmed death-1 ligand 1 expression, Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1, and no untreated brain metastases, carcinomatous meningitis, autoimmune disease, or active malignancy requiring concurrent intervention. A third cohort (A1; n = ∼200) with no prior systemic therapy will have ECOG PS 2 or one or more of the following: asymptomatic untreated brain metastases, renal or hepatic dysfunction, and/or HIV. All patients will receive flat-dose nivolumab (240 mg every 2 weeks) plus weight-based ipilimumab (1 mg/kg every 6 weeks). Endpoints are shown in the table.rnTable: 138 TiP

Study endpoints

rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn rnrn
Number and percentage of patients with high-grade treatment-related select and immune-mediated adverse eventsProgression-free survival
Objective response rate
Duration of response
Patient-reported outcomes based on the Functional Assessment of Cancer Therapy-Lung (FACT-L)

Clinical trial identification


Legal entity responsible for the study

Bristol-Myers Squibb


Bristol-Myers Squibb


L. Paz-Ares: Medical advisor for: Lilly, Roche, MSD, BMS, Celgene, Pfizer, Boehringer Ingelheim, Bayer, Clovis, and Astra Zeneca. C. Chakmakjian: Speaker\'s Bureau for: BMS. N. Ready: Honoraria from: BMS, Merck; Consultant for: BMS, Merck, Novartis, Abbvie. W. Hu, L. Krug, J. Fairchild: Bristol-Myers Squibb employee. All other authors have declared no conflicts of interest.