Author of

• 20039

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  Poster Display Session (ID 63)

  • Event: ELCC 2017
  • Type: Poster Display Session
  • Track:
  • Presentations: 2
  • Moderators:
  • Coordinates: 5/07/2017, 12:30 - 13:00, Hall 1

  • 19894

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    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) (ID 164)

    12:30 - 12:30  |  Author(s): I. Albert
    • Abstract

    Background:
    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 TiPStudy endpointsrn

    rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn rnrn

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

    rn
    
    Clinical trial identification:
    NCT02869789
    
    Legal entity responsible for the study:
    Bristol-Myers Squibb
    
    Funding:
    Bristol-Myers Squibb
    
    Disclosure:
    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.
    
    

  • 19844

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    71TiP - A randomized, phase 3 trial with anti-PD-1 monoclonal antibody pembrolizumab (MK-3475) versus placebo for patients with early stage NSCLC after resection and completion of standard adjuvant therapy (EORTC/ETOP 1416-PEARLS) (ID 399)

    12:30 - 12:30  |  Author(s): I. Albert
    • Abstract

    Background:
    In the last 5 years no major advances have been made in the treatment of early stage NSCLC. Checkpoint inhibitors have shown promising clinical efficacy in advanced, refractory non-small cell lung cancer (NSCLC), but they have not yet been explored in the adjuvant setting. PEARLS (NCT02504372) is international, triple-blinded, placebo-controlled, randomized phase III trial to compare pembrolizumab versus placebo after complete resection of stage IB (T ≥ 4 cm), II and IIIA NSCLC, followed by standard adjuvant chemotherapy, if appropriate as per local guidelines, in patients who have signed the informed consent.
    
    Trial design:
    Eligible patients are those with completely resected stage IB (T ≥ 4 cm), II and IIIA NSCLC that have or have not received adjuvant platinum-based chemotherapy and whose PD-L1 status is known: negative (TPS=0%) versus weak positive (TPS = 1-49%) versus strong positive (TPS≥50%). Co-primary endpoints are disease-free survival in the PD-L1 strong positive subgroup and in the overall population. An HR = 0.78 is targeted for the whole population with 640 disease free survival events from a sample size of 1380 randomized patients. Secondary endpoints include disease-free survival in the PD-L1 positive subgroup, overall survival in each subpopulation and in the overall population, lung cancer specific survival, and safety and tolerability. The exploratory endpoints will assess pharmacokinetics, immunogenicity, quality of life and potential biomarkers of treatment response. Recruitment started in January 2016 and is currently ongoing. As of November 17, 2016, among the 102 randomized patients so far, 44 (43.1%), 32 (31.4%) and 26 (25.5%) patients have negative, weak positive and strong positive PD-L1 status respectively.
    
    Clinical trial identification:
    (EudraCT number 2015-000575-27) (NCT02504372)
    
    Legal entity responsible for the study:
    MSD EORTC, ETOP
    
    Funding:
    MSD
    
    Disclosure:
    All authors have declared no conflicts of interest.