380P - Phase 2 study to evaluate efficacy and safety of combination therapy with nivolumab (NIVO) and ipilimumab(IPI) in patients with previously untreate...

Date 18 November 2017
Event ESMO Asia 2017 Congress
Session Poster lunch
Topics Cancer Immunology and Immunotherapy
Melanoma and other Skin Tumours
Presenter Yoshio Kiyohara
Citation Annals of Oncology (2017) 28 (suppl_10): x113-x116. 10.1093/annonc/mdx667
Authors Y. Kiyohara1, T. Takenouchi2, H. Uhara3, H. Koga4, H. Uchi5, N. Yamazaki6
  • 1Dermatology Division, Shizuoka Cancer Center Hospital, 411-8777 - Shizuoka/JP
  • 2Department Of Dermatology, Niigata Cancer Center Hospital, Niigata/JP
  • 3Department Of Dermatology, Sapporo Medical University, Sapporo/JP
  • 4Department Of Dermatology, Shinshu University School of Medicine, Nagano/JP
  • 5Department Of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka/JP
  • 6Department Of Dermatologic Oncology, National Cancer Center Hospital, Tokyo/JP



NIVO (a PD-1 checkpoint inhibitor) and IPI (a CTLA-4 checkpoint inhibitor) are now approved in several countries including US, EU and Japan for the treatment of advanced melanoma (MEL). A phase 3 study (CheckMate -067) in previously untreated patients (pts), compare the PFS and OS of nivolumab monotherapy to ipilimumab monotherapy and that of nivolumab combined with ipilimumab to ipilimumab monotherapy. Here, we report the latest analysis of the efficacy (ORR, OS, PFS, DOR) and safety of combination therapy with NIVO and IPI in previously untreated Japanese MEL pts.


A phase 2 single arm- study (ONO-4538-17) enrolled Japanese pts aged ≥ 20 years with ECOG PS 0/1 and stage IIIB/IV/recurrent MEL. NIVO (1 mg/kg IV) plus IPI(3mg/kg IV) Q3W for 4 doses then NIVO 3mg/kg Q2W was given to pts until PD, CR or unacceptable toxicity. The primary endpoint was ORR, and secondary endpoints included PFS, OS, DOR and safety. Clinical responses were evaluated by the independent investigator as per RECIST v1.1, including pts with BRAF V600 mutations.


30 MEL pts received NIVO and IPI combination therapy in this study. As previously reported, baseline patient characteristics were similar to other clinical trials and included pts with a median age of 58.5, ECOG PS 1 in 3 pts (10%), and 2 pts (6.7%) were BRAF mutation positive. ORR was 43.3% (95%CI: 25.5 - 62.6). All pts experienced drug-related AEs. Grade 3-4 drug-related AEs were seen in 24 pts (80.0%) and 9 pts (30.0%) discontinued study therapy due to the AEs. Despite these high rates, these AEs were manageable and the drug-related deaths have not been reported. Response rates by subgroup analysis by BRAF status were similar for BRAF wild type and BRAF mutants, respectively.


NIVO and IPI combination therapy showed positive results of ORR in Japanese MEL pts, with results consistent with the larger phase 3 trials (CheckMate-067). The efficacy was verified regardless of BRAF status. The safety profile had no new signal compared to earlier reports.

Clinical trial identification

JAPIC-CTI #142533 (May 9, 2014).

Legal entity responsible for the study

ONO Pharmaceutical, Bristol-Myers Squibb


ONO Pharmaceutical, Bristol-Myers Squibb


Y. Kiyohara: Honoraria was received from ONO Pharmaceutical, Chugai Pharmaceutical, MSD, Bristol-Myers Squibb. Research funding was received from ONO Pharmaceutical, Chugai Pharmaceutical, Bristol-Myers Squibb, MSD, GlaxoSmithKline, Novartis Pharma. T. Takenouchi: Honoraria was received form ONO Pharmaceutical, Chugai Pharmaceutical. H. Uhara: Honoraria was received from ONO Pharmaceutical, Bristol-Myers Squibb, Chugai Pharmaceutical, N. Yamazaki: Honoraria was received from ONO Pharmaceutical, Bristol-Myers Squibb, Novartis Pharma., MSD K, K. Research funding was received from ONO Pharmaceutical, Bristol-Myers Squibb, Novartis Pharma, MSD K, K.

All other authors have declared no conflicts of interest.