481TiP - Checkmate 722: A phase 3 trial of nivolumab with chemotherapy or ipilimumab vs chemotherapy in epidermal growth factor receptor (EGFR)-mutation, T7...

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Cytotoxic agents
Biomarkers
Non-Small-Cell Lung Cancer, Metastatic
Immunotherapy
Presenter Kazuhiko Nakagawa
Citation Annals of Oncology (2016) 27 (suppl_9): ix139-ix156. 10.1093/annonc/mdw594
Authors K. Nakagawa1, J.C. Yang2, K. Park3, Y. Ohe4, Y. Wu5, J. Gainor6, A. Blackwood-Chirchir7, R. Yang8, I. Chang7, T. Mok9
  • 1Department Of Clinical Oncology, Kindai University Hospital, 589-0014 - Osaka/JP
  • 2Department Of Oncology, National Taiwan University Hospital, 100 - Taipei/TW
  • 3Department Of Medicine, Samsung Comprehensive Cancer Center, 06351 - Seoul/KR
  • 4Department Of Thoracic Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 5Department Of Oncology, Guangdong General Hospital, 510080 - Guangzhou/CN
  • 6Department Of Thoracic Oncology, Massachusetts General Hospital, 02114-2696 - Boston/US
  • 7Global Clinical Research, Bristol-Myers Squibb, 08536 - Princeton/US
  • 8Global Biostatistics, Bristol-Myers Squibb, 08536 - Princeton/US
  • 9Department Of Clinical Oncology, The Chinese University of Hong Kong, Shatin/HK

Abstract

Background

Patients with EGFR-mutation–positive advanced NSCLC are treated with targeted EGFR TKI therapy. However, most patients develop disease progression and require treatment with platinum-based chemotherapy, the current standard of care. Nivolumab, an anti-programmed death-1 antibody, is approved for patients with previously treated metastatic NSCLC. In a phase 1 trial (CheckMate 012), combination therapy with nivolumab and either ipilimumab or platinum-based chemotherapy was evaluated as first-line treatment in advanced NSCLC. Both combinations demonstrated a favorable safety profile and promising efficacy. In patients with EGFR-mutation–positive NSCLC, objective response rate (ORR) was 50% (4/8 patients) with nivolumab + ipilimumab and 17% (1/6 patients) with nivolumab + chemotherapy. CheckMate 722 is a phase 3 trial that will evaluate the efficacy of nivolumab + chemotherapy and nivolumab + ipilimumab compared with chemotherapy in patients with EGFR-mutation, T790M-negative recurrent/metastatic NSCLC that has progressed on first-line EGFR TKI therapy.

Trial design

This open-label trial is enrolling adult patients with confirmed stage IV or recurrent EGFR-mutation–positive NSCLC with disease progression after one EGFR TKI therapy and no evidence of exon 20 T790M mutation. Patients with symptomatic brain metastases are ineligible. Patients will be randomized 1:1:1 to one of three treatment groups: nivolumab + pemetrexed/platinum, nivolumab + ipilimumab, or pemetrexed/platinum (see Table). The primary endpoint is progression-free survival (PFS) with nivolumab + chemotherapy or nivolumab + ipilimumab compared with chemotherapy. Secondary endpoints include overall survival, ORR, duration of response, and PFS rate at 9 and 12 months.rn

Table: 481TIP

rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn
ArmIntervention
A: Nivolumab + platinum-doublet chemotherapyQ3W: Nivolumab 360 mg IV
Pemetrexed 500 mg/m2 IV
Cisplatin 75 mg/m2 IV or carboplatin AUC 5 or 6 IV
B: Nivolumab + ipilimumabQ2W: Nivolumab 3 mg/kg IV
Q6W: Ipilimumab 1 mg/kg IV
C: Platinum-doublet chemotherapyQ3W: Pemetrexed 500 mg/m2 IV
Cisplatin 75 mg/m2 IV or carboplatin AUC 5 or 6 IV
rn

AUC = area under the curve; IV = intravenous; Q2W = every 2 weeks; Q3W = every 3 weeks; Q6W = every 6 weeks

rn

Clinical trial indentification

NCT02864251

Legal entity responsible for the study

Bristol-Myers Squibb

Funding

Bristol-Myers Squibb

Disclosure

K. Nakagawa: Paid honoraria by Bristol-Myers Squibb. Conducted research project(s) funded by Bristol-Myers Squibb. J.C-H. Yang: Received grants and/or personal fees for advisory boards and speaking from Boehringer Ingelheim, Eli Lilly, Pfizer, Clovis Oncology, Roche/Genentech/Chugai, Merck Sharp & Dohme, Merck Serono, Astellas, Novartis, Bayer, and Celgene. Y. Ohe: Research grant: AZ, Chugai, Eli Lilly, ONO, BMS, Kyorin, Dainippon-Sumitomo, Pfizer, Taiho, Novartis, & Merck Serono. Honoraria: AZ, Chugai, Lilly, ONO, BMS, Daiichi-Sankyo, Nipponkayaku, BI, Bayer, Pfizer, MSD, Taiho, Clovis, & Sanofi. Y-L. Wu: Personal speaker fees from AstraZeneca, Roche, Eli Lilly, Pfizer, and Sanofi, outside the submitted work. J. Gainor: Conducted research project(s) funded by Novartis, Genentech, Bristol-Myers Squibb, AstraZeneca. Consulting or advisory role for Jounce, Boehringer Ingelheim, Kyowa Hakko Kirin. A. Blackwood-Chirchir, R. Yang, I-F. Chang: Employee of Bristol-Myers Squibb. Owns stock or holds an ownership interest with Bristol-Myers Squibb. T. Mok: Empl: CUHK; LDSHP: Sanomic; Hon. & Consulting: AZ, Roche/GNE, Lilly, Merck Ser, Eisai, BMS, AVEO, Pfizer, Taiho, BI, Novartis, Clovis Onc, Amgen, Janssen, Biomarin; Speakers\' Bur. & Trav. Exp: AZ, Roche, Lilly, BI, Merck Ser, Pfizer, Amgen; Res. Fund: AZ. All other authors have declared no conflicts of interest.