Abstract 1291P
Background
Although rechallenge with anti-cancer drugs that showed efficacy in prior lines of therapy has been broadly accepted in lung cancer, evidence of rechallenge with ICIs has been limited.
Methods
Advanced NSCLC patients who had clinical benefit (CR, PR, or SD ≥ 6 months) from prior ICI (+/- chemo) were prospectively enrolled. All patients had to complete prior ICI ≥ 60 days before registration. Patients were treated with nivolumab (240 mg/body) every 2 weeks until progression. Primary endpoint was ORR. Secondary endpoints consisted of PFS, OS and safety. Based on the hypothesis that this treatment will improve ORR from 10 to 20% (0.05 of one-sided α and power of 0.79), 60 patients are required (Trial Identifier, UMIN000028561).
Results
Between Oct 2017 and Feb 2020, 61 patients were enrolled and 59 were analyzed for efficacy. Of those, median age was 70 (range, 38-81); male/female 43/16; never smoker/smoker 10/49; ECOG performance status 0/1 22/37; Non-squamous/squamous/others 34/21/4. Regarding efficacy with prior ICI, 41 had CR or PR and 18 had SD ≥ 6 months. ORR was 8.5% (95%CI: 2.8-18.7%) and clinical backgrounds (histology, PD-L1 expression at diagnosis, efficacy of prior ICI) were not predictive. Median PFS was 2.6 months (95%CI: 1.6 to 2.8 months) and median OS was 11.0 months (95%CI: 9.0 to 14.5 months). On the other hand, 5 responders had 11.1 months of median PFS and they were all alive at data cut-off (survival time ranged from 8.4 to 27.7 months). Common adverse events were skin disorders (23%), malaise (20%) and hypoalbuminemia (15%). No treatment-related deaths occurred.
Conclusions
Our selection criteria did not work for Nivolumab rechallenge, however, small fraction had clinical benefit. Development of predictive biomarker is warranted.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
West Japan Oncology Group.
Funding
Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb Company.
Disclosure
S. Teraoka: Financial Interests, Personal, Invited Speaker: Chugai Pharma; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Eli Lilly. H. Akamatsu: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: CareNet; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical; Financial Interests, Personal, Research Grant: Chugai Pharmaceutical; Financial Interests, Personal, Research Grant: MSD. S. Takamori: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical. H. Hayashi: Financial Interests, Personal, Invited Speaker: AstraZeneca K.K.; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim Japan Inc.; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb Co. Ltd.; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal, Invited Speaker: Eli Lilly Japan K.K.; Financial Interests, Personal, Invited Speaker: MSD K.K.; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd.; Financial Interests, Personal, Invited Speaker: Pfizer Japan Inc.; Financial Interests, Personal, Invited Speaker: Shanghai Haihe Biopharm; Financial Interests, Personal, Invited Speaker: Kyorin Pharmaceutical Co. Ltd.; Financial Interests, Personal, Invited Speaker: Novartis Pharma K.K.; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co. Ltd.; Financial Interests, Personal, Research Grant: AstraZeneca K.K.; Financial Interests, Personal, Research Grant: Boehringer Ingelheim Japan Inc.; Financial Interests, Personal, Research Grant: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal, Research Grant: Ono Pharmaceutical Co. Ltd. S. Miura: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Kyowa Hakko Kirin; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AbbVie; Financial Interests, Personal, Invited Speaker: Nippon Kayaku. A. Hata: Financial Interests, Personal, Invited Speaker: Eli Lilly, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Research Grant: Eli Lilly; Financial Interests, Personal, Research Grant: Boehringer Ingelheim; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim. Y. Toi: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb Co. Ltd.; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal, Invited Speaker: MSD K.K.; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd. Y. Shiraishi: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal, Research Grant: Chugai Pharmaceutical Co. Ltd. N. Mamesaya: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal, Invited Speaker: MSD K.K.; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd.; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical; Financial Interests, Personal, Research Grant: Boehringer Ingelheim. Y. Sato: Financial Interests, Personal, Invited Speaker: Chugai Pharma; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co.; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Nippon Kayaku; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb. N. Furuya: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb Co. Ltd.; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: MSD K.K.; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical; Financial Interests, Personal, Invited Speaker: Kyowa Hakko Kirin; Financial Interests, Personal, Invited Speaker: Pfizer Inc. Y. Koh: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Guardant Health; Financial Interests, Personal, Invited Speaker: Hitachi High Technologies; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board: Tosoh Corp.; Financial Interests, Personal, Research Grant: Boehringer Ingelheim; Financial Interests, Personal, Research Grant: Terumo; Financial Interests, Personal, Research Grant: Tosoh Corp.; Financial Interests, Personal, Research Grant: Toppan Print; Financial Interests, Personal, Research Grant: OnChip Biotechnologies. T. Yamanaka: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Otsuka; Financial Interests, Personal, Invited Speaker: Ono; Financial Interests, Personal, Invited Speaker: Kyowa Kirin; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Gilead Sciences; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Chugai; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: EPS. N. Yamamoto: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Research Grant: AstraZeneca K.K.; Financial Interests, Personal, Research Grant: Astellas Pharma Inc.; Financial Interests, Personal, Research Grant: A2 Healthcare Corporation; Financial Interests, Personal, Research Grant: Boehringer Ingelheim Japan Inc.; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Chugai Pharmaceutical; Financial Interests, Personal, Research Grant: CMIC Shift Zero K.K; Financial Interests, Personal, Research Grant: Daiichi Sankyo; Financial Interests, Personal, Research Grant: Eli Lilly; Financial Interests, Personal, Research Grant: IQVIA services Japan; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: Ono Pharmaceutical Co. Ltd.; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Research Grant: PPD-SNBL K.K; Financial Interests, Personal, Research Grant: Takeda Pharmaceutical; Financial Interests, Personal, Research Grant: Taiho Pharmaceutical; Financial Interests, Personal, Research Grant: Terumo Corporation; Financial Interests, Personal, Research Grant: Toppan Printing Co., Ltd. K. Nakagawa: Financial Interests, Personal, Invited Speaker: AstraZeneca K.K.; Financial Interests, Personal, Invited Speaker: Nichi-Iko Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: Astellas Pharma Inc.; Financial Interests, Personal, Invited Speaker: Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: MSD K.K.; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb Company; Financial Interests, Personal, Invited Speaker: Nippon Boehringer Ingelheim Co., Ltd. Nippon Boehringer Ingelheim Co., Ltd.; Financial Interests, Personal, Invited Speaker: Eli Lilly Japan K.K.; Financial Interests, Personal, Invited Speaker: Novartis Pharma K.K.; Financial Interests, Personal, Invited Speaker: SymBio Pharmaceuticals Limited; Financial Interests, Personal, Invited Speaker: Pfizer Japan Inc.; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: Clinical Trial Co., Ltd.; Financial Interests, Personal, Invited Speaker: Nanzando Co., Ltd.; Financial Interests, Personal, Invited Speaker: Medicus Shuppan, Publishers Co., Ltd.; Financial Interests, Personal, Invited Speaker: Yodosha Co., Ltd.; Financial Interests, Personal, Invited Speaker: Care Net, Inc.; Financial Interests, Personal, Invited Speaker: Nikkei Business Publications, Inc.; Financial Interests, Personal, Invited Speaker: Reno. Medical K.K.; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo Co., Ltd.; Financial Interests, Personal, Invited Speaker: Kyorin Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: Thermo Fisher Scientific K.K.; Financial Interests, Personal, Invited Speaker: Medical Review Co., Ltd.; Financial Interests, Personal, Invited Speaker: Yomiuri Telecasting Corporation; Financial Interests, Personal, Invited Speaker: Roche Diagnostics K.K.; Financial Interests, Personal, Invited Speaker: Nippon Kayaku Co., Ltd.; Financial Interests, Personal, Invited Speaker: Bayer Yakuhin, Ltd.; Financial Interests, Personal, Invited Speaker: Merck Biopharma Co., Ltd.; Financial Interests, Personal, Invited Speaker: Medical Mobile Communications co., Ltd.; Financial Interests, Personal, Invited Speaker: AbbVie Inc.; Financial Interests, Personal, Invited Speaker: 3H Clinical Trial Inc.; Financial Interests, Personal, Research Grant: MSD K.K.; Financial Interests, Personal, Research Grant: A2 Healthcare Corp.; Financial Interests, Personal, Research Grant: inVentiv Health Japan; Financial Interests, Personal, Research Grant: Astellas Pharma Inc.; Financial Interests, Personal, Research Grant: Daiichi Sankyo Co., Ltd.; Financial Interests, Personal, Research Grant: Novartis Pharma K.K.; Financial Interests, Personal, Research Grant: AbbVie Inc.; Financial Interests, Personal, Research Grant: Quintiles Inc. / IQVIA Services Japan K.K.; Financial Interests, Personal, Research Grant: Icon Japan K.K.; Financial Interests, Personal, Research Grant: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Personal, Research Grant: Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Research Grant: EP-CRSU CO., LTD.; Financial Interests, Personal, Research Grant: Gritsone Oncology.INC; Financial Interests, Personal, Research Grant: Linical Co., Ltd.; Financial Interests, Personal, Research Grant: Eli Lilly Japan K.K.; Financial Interests, Personal, Research Grant: Eisai Co., Ltd.; Financial Interests, Personal, Research Grant: Bristol Myers Squibb Company; Financial Interests, Personal, Research Grant: Nippon Boehringer Ingelheim Co., Ltd.; Financial Interests, Personal, Research Grant: Taiho Pharmaceutical Co., Ltd.; Financial Interests, Personal, Research Grant: Pfizer Japan Inc.; Financial Interests, Personal, Research Grant: Parexel International Corp.; Financial Interests, Personal, Research Grant: SymBio Pharmaceuticals Limited; Financial Interests, Personal, Research Grant: Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Research Grant: Merck Serono Co., Ltd./ Merck Biopharma Co., Ltd.; Financial Interests, Personal, Research Grant: AstraZeneca K.K.; Financial Interests, Personal, Research Grant: CMIC Shift Zero K.K.; Financial Interests, Personal, Research Grant: Kissei Pharmaceutical Co., Ltd.; Financial Interests, Personal, Research Grant: Kyowa Hakko Kirin Co., Ltd; Financial Interests, Personal, Research Grant: EPS Corporation; Financial Interests, Personal, Research Grant: Bayer Yakuhin, Ltd.; Financial Interests, Personal, Research Grant: Syneos Health; Financial Interests, Personal, Research Grant: EPS International Co., Ltd.; Financial Interests, Personal, Research Grant: Pfizer R&D Japan G.K.; Financial Interests, Personal, Invited Speaker: Otsuka Pharmaceutical Co., Ltd.; Financial Interests, Personal, Advisory Board: Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Advisory Board: KYORIN Pharmaceutical Co., Ltd.; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Advisory Board: Pfizer Japan Inc.; Financial Interests, Personal, Advisory Board: Eli Lilly Japan K.K.