225P - Nivolumab for cancer of unknown primary (CUP): Clinical efficacy and biomarker analysis from NivoCUP2 expanded access program (WJOG14620M)

Background

Nivolumab, based on results from the phase II NivoCUP trial, has been available in Japan for CUP. However, beyond NivoCUP, there are no additional data available for nivolumab in CUP. Here, we present the first biomarker analysis and efficacy data from an expanded access program (EAP), NivoCUP2 (WJOG14620M).

Methods

NivoCUP2 enrolled patients with CUP regardless of treatment history except anti-PD-1 treatment. Patients received nivolumab at either 240 mg/body every 2 weeks or 480 mg/body every 4 weeks. Biomarker analysis included peripheral blood immunoassay, gene mutation analysis, gene expression analysis, tissue of origin analysis, and T-cell repertoire analysis.

Results

Fifty-three patients received nivolumab, including 22 treatment-naïve and 31 previously treated individuals. The objective response rate (ORR) was 17.0% (95% CI, 8.1–29.8), with a disease control rate of 50.9% (95% CI, 36.8–64.9), a median progression-free survival of 4.5 months (95% CI, 2.9–6.3 months), and an overall survival of 17.5 months (95% CI, 11.9–25.1) in overall population. No new safety signals emerged. The clinical efficacy of nivolumab was notable in tumors with higher levels of programmed death ligand 1 (PD-L1) expression, showing an ORR of 33.3% for PD-L1 TPS 1% and higher, versus 7.1% for PD-L1 TPS less than 1%. Primary site prediction was conducted in 29 cases, with squamous cell carcinoma of the lung (n=7) and renal cell carcinoma (n=6) being the most frequently predicted tumor types. There were 12 patients with nodal metastasis only, and these populations had a higher ORR than the 41 patients with extranodal metastasis (25.0% vs. 14.6%) along with high PD-L1 expression in such nodal-only metastatic population. Responders exhibited enriched CD45 negative CD4 T cells and a low frequency of regulatory T cells in baseline PBMC.

Conclusions

Our EAP confirmed clinical efficacy of nivolumab for patients with CUP. This study will allow us to understand the tumor-agnostic biomarkers for nivolumab.

Clinical trial identification

jRCT2051200146, UMIN000044038.

Editorial acknowledgement

Legal entity responsible for the study

West Japan Oncology Group.

Funding

Ono Pharmaceutical Co., Ltd.

Disclosure

J. Tanizaki: Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim Japan Inc, Bristol Myers Squibb Co. Ltd, Chugai Pharmaceutical Co., Ltd, Daiichi Sankyo Co., Ltd, Eli Lilly Japan K.K, Janssen Pharmaceutical K.K, MSD K.K, Nihon Medi-Physics Co., Ltd, Nippon Kayaku Co., Ltd, Taiho Pharmaceutical Co. Ltd. K, Ono pharmaceutical Co. Ltd, Pfizer Japan Inc, AstraZeneca K.K., Takeda Pharmaceuticals; Financial Interests, Personal, Advisory Board: AstraZeneca K.K., AbbVie GK; Non-Financial Interests, Member: ASCO, JSMO, Japan Lung Cancer Society, ESMO, IASLC. K. Yonemori: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, Sanofi, Genmab, Gliad, OncoXerna, Takeda, Novartis, MSD; Financial Interests, Personal, Invited Speaker: Pfizer, Eisai, AstraZeneca, Eli Lilly, Takeda, Chugai, Fuji Film Pharma, PDR Pharma, MSD, Ono, BMS, Boehringer Ingelheim, Daiichi Sankyo, Bayer, Janssen, Sanofi; Financial Interests, Institutional, Local PI: MSD, Daiichi Sankyo, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seagen, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirrin, Nihon Kayaku, Haihe. Y. Takiguchi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, AstraZeneca, Chugai Pharma, Boehringer Ingelheim, Daiichi Sankyo, Taiho Pharmaceutical, Bristol Myers Squibb Japan, Lilly, Pfizer, Novartis, Kyowa Kirin International, MSD, Eisai, Takeda, AMGEN, Thermofisher, Milliad Genetics; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Other, Member of Ethics Committee: Oncolys BioPharma; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Chugai Pharma; Financial Interests, Institutional, Coordinating PI: MSD Oncology, AstraZeneca, AbbVie. K. Komine: Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo, Bayer, Nihonkayaku, Kyowa Kirin, Incyte Japan, Chugai Pharma, Bristol Myers Squibb Japan. K. Hirata: Financial Interests, Personal, Invited Speaker: Eli Lilly Japan K.K., Taiho Pharmaceutical Co., Ltd, Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb Company, Yakult Honsha Co., Ltd.; Financial Interests, Personal and Institutional, Research Grant: Taiho Pharmaceutical Co., Ltd, Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb Company, Pfizer Inc.. T. Onoe: Financial Interests, Personal, Advisory Role: Eisai Inc.; Financial Interests, Personal, Speaker’s Bureau: Eisai Inc., Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bristol Myers Squibb Co. T. Ishiguro: Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical, Eisai Co., Ltd. Y. Togashi: Financial Interests, Personal, Speaker, Consultant, Advisor: Ono, BMS, AstraZeneca, Eisai, MSD, Chugai; Financial Interests, Personal, Research Funding: Ono, BMS, Daiichi Sankyo, Kotai, Kortuc, Janssen, AstraZeneca. K. Sakai: Financial Interests, Personal, Invited Speaker: Qiagen, Inc., Takeda Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd.. K. Nishio: Financial Interests, Personal, Invited Speaker: AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Novartis Pharma K.K., MSD K.K., Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Daiichi Sankyo, Invitae Japan, Nichirei Biosciences Inc., Maruho Co., Ltd.; Financial Interests, Personal, Advisory Board: Otsuka Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Limited., Guardant Health Inc., Janssen Pharmaceutical; Financial Interests, Personal, Research Grant: West Japan Oncology Group, Nichirei Biosciences Inc., Hitachi, Ltd., osakaminami hospital, Sysmex Corporation, Otsuka Pharmaceutical, Thoracic Oncology Research Group, University Public Corporation Osaka.. K. Nakagawa: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Nippon Boehringer Ingelheim Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Incyte biosciences Japan, Merck Biopharma Co., Ltd., Janssen Pharmaceutical K.K., Bristol Myers Squibb Company, Medical Mobile Communications co., Ltd, Novartis Pharma K.K., Daiichi Sankyo Co., Ltd., Otuka Pharmaceutical Factory, Inc., M3, Inc., Hisamitsu Pharmaceutical Co., Inc., Global Health Consulting Japan Co., Ltd., The Yomiuri Shimbun; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K.; Financial Interests, Personal, Writing Engagement: Yodosha Co., Ltd.; Financial Interests, Institutional, Research Grant: Amgen Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., EP-Crsu Co., Ltd., EPS Corporation., Eisai Co., Ltd., GSK K.K., Iqvia Services Japan K.K., Janssen Pharmaceutical K.K., Kobayashi Pharmaceutical Co., Ltd., MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., Nippon Kayaku Co., Ltd., PRA Healthsciences, SRL Medisearch Inc., Syneos Health Clinical K.K., Sanofi K.K., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., CMIC CO., Ltd., Pfizer R&D Japan G.K., Labcorp Development Japan K.K., Pfizer Japan Inc., Shionogi & Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Astellas Pharma Inc., Ascent Development Services, Eisai Inc., Bayer Yakuhin, Ltd, AstraZeneca K. K., AbbVie Inc., A2 Healthcare Corp., Japan Clinical Cancer Research Organization, Thoracic Oncology Research Group. H. Hayashi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd., Bristol Myers Squibb Co. Ltd, AstraZeneca K.K, Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo K.K, Eli Lilly Japan K.K, Merck Biopharma Co. Ltd, MSD K.K., Novartis Pharmaceuticals K.K, Pfizer, Takeda Pharmaceutical Co. Ltd; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb Co. Ltd, Eli Lilly Japan K.K, Pfizer, AstraZeneca K.K, Daiichi Sankyo Co. Ltd.; Financial Interests, Personal, Royalties, Currently no provided: Sysmex; Financial Interests, Personal, Steering Committee Member: Janssen Pharmaceutical K.K., GSK plc., Daiichi Sankyo, Inc.; Financial Interests, Institutional, Local PI: IQVIA Services Japan K.K, Syneos Health Clinical K.K., EPS Corporation., Nippon Kayaku Co., Ltd., Takeda Pharmaceutical Co., Ltd., MSD K.K., Amgen Inc., Taiho Pharmaceutical Co., Ltd., Bristol Myers Squibb Company, Janssen Pharmaceutical K.K., CMIC CO., Ltd., Pfizer R&D Japan G.K., Labcorp Development Japan K.K., Kobayashi Pharmaceutical Co., Ltd., Pfizer Japan Inc., AbbVie Inc., A2 Healthcare Corp., Eli Lilly Japan K.K., Medpace Japan KK, EPS International Co., Ltd,., Covance Japan Inc., EP-Crsu CO., LTD., GSK K.K., Sanofi K.K., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., PRA Health Sciences Inc., Astellas Pharma Inc., Ascent Development Services, AstraZeneca K.K., Daiichi Sankyo Co., Ltd., Novartis Pharma K.K., Merck Biopharma Co., Ltd, Mochida Pharmaceutical Co., Ltd., Japan Clinical Research Operations; Financial Interests, Institutional, Research Grant: Japanese Gastric Cancer Association, Clinical Research Support Center Kyushu, Japan Clinical Caner Research Organization, Ono Pharmaceutical Co., Ltd., Medical Research Support, Eisai Co., Ltd, Shionogi & Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Bayer Yakuhin, Ltd, Kyowa Kirin Co., Ltd.; Financial Interests, Institutional, Funding: SRL Medisearch Inc., Eisai Inc., Thoracic Oncology Research Group(TORG), West Japan Oncology Group (WJOG), Comprehensive Support Project for Oncological Research of Breast Cancer (CSPOR-BC), Mebix, Inc.; Non-Financial Interests, Member: West Japan Oncology Group, Japanese Society of Medical Oncology. All other authors have declared no conflicts of interest.