Multicenter phase II study of cisplatin and gemcitabine plus necitumumab in patients with unresectable, advanced lung squamous cell carcinoma who have progressed on or after initial treatment with immune checkpoint inhibitors plus platinum-based chemotherapy: WJOG14120L NESSIE study

BackgroundCisplatin and gemcitabine plus necitumumab (CGN) is one of the first-line standard therapies for patients (pts) with advanced lung squamous cell carcinoma (LSqCC). However, the efficacy and safety of CGN in pts who have progressed on or after initial treatment with immune checkpoint inhibitors (ICIs) plus platinum-based chemotherapy (PBC) remains to be elucidated.MethodsThis multicenter single-arm phase II study evaluated the efficacy and safety of CGN in pts who have pathologically proven advanced LSqCC, performance status of 0-1, aged 20 or older, and have progressed on or after initial treatment combining ICIs plus PBC including concurrent chemoradiotherapy followed by maintenance ICI for locally advanced disease. CGN (cisplatin 75 mg/m2 on day 1 and gemcitabine 1250 mg/m2 on days 1 and 8 of up to four cycles; necitumumab 800 mg/body on days 1 and 8) was administered triweekly until progressive disease or unacceptable toxicity. Primary endpoint is objective response rate (ORR). The ORR of the null and alternative hypotheses were set at 23% and 40%, respectively, with α error of 0.1 (one-sided) and β error of 0.2, requiring 41 pts. (Registration: jRCTs051200138).ResultsBetween Feb-2021 and Apr-2023, 46 pts (median age 68 [range 52-78] years, PS 0/1: 16/30, male/female: 42/4) were enrolled. ORR was 26.1% (80% confidence interval (CI), 17.7–36.2). Disease control rate was 87.0% (95%CI, 73.7-95.1). The median progression-free survival and overall survival were 4.39 months (95%CI, 4.14-5.45) and 12.29 months (95%CI, 8.15-15.15), respectively. Grade 3 or 4 adverse events included febrile neutropenia (14.9%), acneiform eruption (10.6%) and hypomagnesemia (4.3%). Neither any grade pneumonitis nor treatment-related death were observed.ConclusionsCGN demonstrated moderate efficacy and good tolerability in patients who have progressed on or after front-line ICIs plus PBC, although the primary endpoint was not met.Clinical trial identificationjRCTs051200138.Legal entity responsible for the studyWest Japan Oncology Group.FundingNippon Kayaku Co., Ltd.DisclosureH. Yoshioka: Financial Interests, Personal, Invited Speaker, Lecture fee: Eli Lilly Japan K.K., Takeda Pharmaceutical, Nippon Boehringer Ingelheim, Nippon Kayaku, Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb, MSD, AstraZeneca, Ono Pharmaceutical, Novartis Pharma, Kyowa Kirin, Otsuka Pharmaceutical, Amgen, Pfizer, Daiichi Sankyo, Nipro Pharma, Merck Biopharma; Financial Interests, Personal, Other, Consulting fee: Delta-Fly Pharma, Inc.; Financial Interests, Institutional, Local PI: Daiichi Sankyo, AstraZeneca, Janssen Pharmaceutical, MSD, Novartis Pharma; Financial Interests, Institutional, Coordinating PI: Delta-Fly Pharma, Boehringer Ingelheim. K. Mori: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, Eli Lilly Japan, Chugai Pharma. 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. K. Azuma: Financial Interests, Personal, Invited Speaker, Lecture fee: AstraZeneca, MSD, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb, Takeda Pharmaceutical. H. Akamatsu: Financial Interests, Personal, Advisory Board: Amgen Inc., Janssen Pharmaceutical K.K., Sandoz; Financial Interests, Personal, Invited Speaker: AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., MSD K.K., Nippon Kayaku. Co. Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd., Pfizer Inc., Takeda Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd.; Financial Interests, Institutional, Coordinating PI: Amgen Inc., Chugai Pharmaceutical Co. Ltd. H. Daga: Financial Interests, Personal, Invited Speaker: Chugai pharmaceutical, AstraZeneca. T. Yamaguchi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Ono Pharmaceutical, Chugai Pharmaceutical, MSD, Bristol Myers Squibb, Taiho Pharmaceutical, Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Daiichi Sankyo. N. Yamamoto: Financial Interests, Personal, Invited Speaker: MSD K.K, AstraZeneca, Ono Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Novartis, Pfizer Inc., Amgen Inc., Merck Biopharma; Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical CO., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Novartis; Financial Interests, Institutional, Research Grant: MSD K.K; Financial Interests, Institutional, Local PI: AstraZeneca, Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Amgen Inc., Janssen Pharmaceutical K.K., Novartis, Eisai, Eli Lilly Japan; Financial Interests, Institutional, Funding: Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Sanofi. 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 Health Sciences, 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. T. Kurata: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Pfizer, Bristol Myers, Takeda, Eli Lilly, Chugai, Nipponkayaku, Ono; Financial Interests, Institutional, Local PI: MSD, Takeda, Janssen, AstraZeneca, Daiichi Sankyo, Chugai, Amgen, Novartis, Ono. All other authors have declared no conflicts of interest.