406P - Phase 2 study of nivolumab (NIVO) in Japanese patients with previously untreated advanced melanoma: long-term efficacy and safety

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Immunotherapy
Skin Cancers
Presenter Naoya Yamazaki
Citation Annals of Oncology (2016) 27 (suppl_9): ix126-ix129. 10.1093/annonc/mdw589
Authors N. Yamazaki1, H. Uhara2, Y. Kiyohara3
  • 1Department Of Dermatologic Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 2Department Of Dermatology, Shinshu University School of Medicine, 390-8621 - Nagano/JP
  • 3Shizuoka Cancer Center Hospital, Shizuoka Cancer Center Hospital, 411-8777 - Shizuoka/JP



NIVO (a PD-1 checkpoint inhibitor) is now approved in several countries including US, EU and Japan for the treatment of advanced melanoma (MEL). A phase 3 study (CheckMate -066) in previously untreated patients (pts), demonstrated that NIVO improved OS compared with DTIC. Here, we report the latest analysis of the efficacy (ORR, OS, PFS, DOR) and safety of NIVO in previously untreated Japanese MEL pts.


A phase 2 single arm- study (ONO-4538-08) enrolled Japanese pts aged ≥ 20 years with ECOG PS 0/1 and stage IIIB/IV/recurrent MEL. NIVO (3 mg/kg IV Q2W) was given to pts until PD, CR or unacceptable toxicity. The primary endpoint was ORR, and secondary endpoints included OS, PFS and DOR. Clinical responses were assessed by investigators as per RECIST v1.1, including pts with BRAF V600 mutations.


24 MEL pts received Nivo in this study. As previously reported, baseline patient characteristics were similar to other clinical trials and included pts with a median age of 63, ECOG PS 1 in 8 pts (33%), and 6 pts (25%) were BRAF mutation positive. With a median follow-up of 18.8 months (range 2.0-21.5), the ORR was 34.8% (90% CI: 20.8-51.9). The DOR was maintained for ≥12 months in 6 of 10 (60%) of pts with a response. The median OS was not reached. The 12- and 18-month survival rates were 69.6% and 56.5%, respectively. 20 pts (83.3%) experienced drug-related AEs. Grade 3-4 drug-related AEs were seen in 3 pts (12.5%) including colitis, renal function disorder, anemia, and fever (4.2% each), leading to treatment discontinuation in 1 pt (4.2%) . No drug-related death was reported. The response rate by subgroup analysis by BRAF status was 23.5% and 66.7% for BRAF wild-type and BRAF mutant, respectively.


NIVO showed a promising result of OS in Japanese MEL pts and a long-lasting DOR in the pts, with results consistent with the larger phase 3 NIVO trials. The efficacy was verified regardless of BRAF status. With longer follow-up, the frequency and incidence of AEs was similar to earlier reports.

Clinical trial indentification

JAPIC-CTI #142533


March 2014

Legal entity responsible for the study

Ono Pharmaceutical


Funded by Ono Pharmaceutical


N. Yamazaki: Advisory Board Role: Chugai Pharmaceutical, Bristol-Myers Squibb, Ono Pharmaceutical. Honoraria: Chugai Pharmaceutical, Bristol-Myers Squibb, Ono Pharmaceutical, GlaxoSmithKline, Takeda Pharmaceutical, Astra Zeneca, Boehringer Ingelheim, Maruho. H. Uhara: Advisory Board Role:Chugai Pharmaceutical, Bristol-MyersSquibb, Ono Pharmaceutical, MSD. Honoraria: Chugai Pharmaceutical, Bristol-Myers Squibb, Ono Pharmaceutical MSD. Speaker\'s Bureau:Chugai Pharmaceutical, Bristol-Myers Squibb, Ono Pharmaceutical. Y. Kiyohara: Advisory Board Role: Chugai Pharmaceutical, Bristol-Myers Squibb, Ono Pharmaceutical, MSD, Novartis Pharma. Honoraria and Speaker\'s Bureau:Chugai Pharmaceutical, Bristol-Myers Squibb, Ono Pharmaceutical.