Phase II study of neoadjuvant concurrent chemo-immuno-radiation therapy followed by surgery and adjuvant immunotherapy for resectable stage IIIA-B N2 non-small cell lung cancer: SQUAT trial (WJOG 12119L)

ABSTRACT

Background: Neoadjuvant chemo-immunotherapy (CheckMate 816 regimen) has become a standard of care in treatment of resectable non-small cell lung cancer (NSCLC) patients in some countries. Addition of radiation therapy (RT) may further improve local control in locally advanced NSCLC patients. Here, we report the primary endpoint, major pathologic response (MPR), of the SQUAT trial (WJOG 12119L, JapicCTI- 195069)-a multicenter, prospective, single-arm, phase II trial of neoadjuvant concurrent chemo-immuno-radiation therapy followed by surgical resection and adjuvant immunotherapy for resectable stage IIIA-B N2 NSCLC. Method(s) Patients with resectable stage IIIA-B N2 NSCLC received concurrent chemoradiotherapy [weekly paclitaxel (40 mg/m2)/carboplatin (AUC 2) for 5 weeks plus involved-field RT 50 Gy] and immunotherapy [durvalumab (1500 mg) Q4W for 2 cycles] followed by surgical resection and adjuvant immunotherapy (durvalumab for up to 1 year). The primary endpoint was MPR rate according to an independent central review (ICR). We assumed the threshold of the MPR rate to be 40% and the expected rate to be 65% with a significance level alpha=0.05 (one-sided) and power 0.8. The sample size was 31 patients, including the 10% ineligible patients. Result(s) Between Jan 2020 and Feb 2022, 31 patients were enrolled from 10 institutions in Japan. Thirty-one patients were evaluated for safety, and 30 patients for efficacy. Of 30 patients (median age, 64 years), 70% and 63% had clinical stage IIIA and non-squamous histology, respectively. The MPR and pathological complete response (pCR) rates by ICR were 63% (90% CI, 47-78, 95% CI, 44-80) and 20% (95% CI, 8-39), respectively. Complete resection was not performed due to adverse events (2 pts) and disease progression (3 pts). Among 25 patients who received complete resection, the MPR and pCR rates were 76% (95% CI, 55-91) and 24% (95% CI, 9-45), respectively. No 30-day postoperative mortality was reported. Conclusion(s) The primary endpoint of MPR rate was met in SQUAT trial. This result suggests that this treatment strategy is promising for resectable stage IIIA-B N2 NSCLC. Clinical trial identification JapicCTI-195069. Legal entity responsible for the study WJOG (West Japan Oncology Group). Funding(s) AstraZeneca. Disclosure T. Miyoshi Financial Interests, Institutional, Research Grant AstraZeneca. A. Hamada Financial Interests, Personal, Invited Speaker AstraZeneca, Chugai, Ono Pharmaceuticals;Financial Interests, Personal, Advisory Board AstraZeneca;Financial Interests, Institutional, Research Grant AstraZeneca. J. Soh Financial Interests, Personal, Invited Speaker Ethicon, Covidien, Intutive;Financial Interests, Institutional, Research Grant AstraZeneca. A. Hata Financial Interests, Institutional, Research Grant MSD, Eli Lilly, Boehringer Ingelheim, AstraZeneca;Financial Interests, Personal, Invited Speaker Eli Lilly, Chugai, Pfizer, AstraZeneca, Boehringer Ingelheim. Y. Yatabe Financial Interests, Personal, Invited Speaker MSD, Chugai-pharma, AstraZeneca, Pfizer, Thermo Fisher Science, ArcherDx, Novartis, Elli-Lily, Daiichi Sankyo, Jansen-Pharma, Amgen;Financial Interests, Institutional, Research Grant Thermo Fisher Science, ArcherDx, AstraZeneca. J. Suzuki Financial Interests, Institutional, Research Grant AstraZeneca. M. Tsuboi Financial Interests, Personal, Invited Speaker, Lecture Johnson & Johnson Japan;Financial Interests, Personal, Advisory Board, Lectures, Advisory boards AstraZeneca KK, Chugai Pharmaceutical Co.,Ltd, MSD;Financial Interests, Personal, Invited Speaker, Lectures Eli Lilly Japan, Bristol Myers Squibb KK, Teijin Pharma, Taiho Pharma, Medtronic Japan, ONO Pharmaceutical Co.,Ltd;Financial Interests, Personal, Advisory Board, Advisory boards Novartis;Financial Interests, Personal, Invited Speaker Daiichi Sankyo company limited, MSD, AstraZeneca, Novartis;Financial Interests, Institutional, Research Grant Beohringer-Ingelheim Japan, MSD, AstraZeneca KK, Ono Pharmaceutical Co.,Ltd, Bristol Myers Squibb KK, Novartis;Financial Interests, Institutional, Invited Speaker Eli Lilly Japan. H. Horinouchi Financial Interests, Personal, Invited Speaker AstraZeneca, Eli Lilly, BMS/ONO, Merck Sharp & Dohme, Roche/Chugai, Novartis, Pfizer, Boehringer Ingelheim, Kyowa-Kirin, Nihon Kayaku, AbbVie, Roche/Chugai;Financial Interests, Personal, Advisory Board AstraZeneca, Eli Lilly, BMS/ONO, Merck Sharp & Dohme, Roche/Chugai, Amgen, Nihon Kayaku;Financial Interests, Institutional, Research Grant Roche/Chugai, Merck Sharp & Dohme, Daiichi Sankyo, ONO pharmaceutical, AstraZeneca;Financial Interests, Institutional, Invited Speaker AbbVie. I. Yoshino Financial Interests, Institutional, Research Grant AstraZeneca. T. Masayuki Financial Interests, Institutional, Research Grant AstraZeneca. S. Toyooka Financial Interests, Personal, Invited Speaker Chugai, Taiho, Ono Pharmaceuticals, Kyorin, Daiichi Sankyo, Medtronic, Johnson and Johnson;Financial Interests, Personal, Advisory Role Kyorin;Financial Interests, Institutional, Research Grant Illumina, Eurofins, Taiho, Chugai, Eli Lilly, AstraZeneca. M. Okada Financial Interests, Institutional, Research Grant AstraZeneca. T. Go Financial Interests, Institutional, Research Grant AstraZeneca. M. Yamashita Financial Interests, Institutional, Research Grant AstraZeneca. N. Yamamoto Financial Interests, Personal, Invited Speaker MSD K.K, AstraZeneca, Ono Pharmaceutical Co., Ltd., Thermo Fisher Scientific, Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Boehringer Ingelheim, Novartis, Pfizer Inc., Bristol Myers Squibb, Nippon Kayaku, GlaxoSmithKline K.K., Sanofi K.K., Hisamitsu Pharmaceutical Co.,Inc., Merk biopharma;Financial Interests, Personal, Advisory Board AstraZeneca, Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Boehringer Ingelheim, Novartis, Bristol Myers Squibb, Nippon Kayaku, Life Technologies Japan Ltd., Amgen Inc., Guardant Health Japan, Janssen Pharmaceutical K.K.;Financial Interests, Institutional, Research Grant MSD K.K;Financial Interests, Institutional, Invited Speaker AstraZeneca, Ono Pharm ceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Pfizer Inc., Amgen Inc., Janssen Pharmaceutical K.K.;Financial Interests, Institutional, Funding: Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Toppan printing, Terumo. K. Nakagawa Financial Interests, Personal, Invited Speaker Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Amgen Inc., Nippon Kayaku Co., Ltd., 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., CMIC ShiftZero K.K., Life Technologies Japan Ltd., Neo Communication, Merck Biopharma Co., Ltd., Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Co., Ltd., 3H Clinical Trial Inc., Care Net, Inc., Medical Review Co., Ltd., Medical Mobile Communications co., Ltd, Yodosha Co., Ltd., Nikkei Business Publications, Inc., Japan Clinical Research Operations, CMIC Co., Ltd., Novartis Pharma K.K., Taiyo Pharma Co., Ltd.;Financial Interests, Personal, Advisory Board Ono Pharmaceutical Co.,Ltd., Eli Lilly Japan K.K.;Financial Interests, Institutional, Other, patents sales fee Daiichi Sankyo Co., Ltd.;Financial Interests, Institutional, Research Grant Parexel International Corp., Pra Healthsciences, Eps Corporation., Kissei Pharmaceutical Co., Ltd., EPS International Co.,Ltd,., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co.,Ltd., MSD K.K., Ono Pharmaceutical Co.,Ltd., PPD-SNBL K.K, SymBio Pharmaceuticals Limited., IQVIA Services Japan K.K., Syneos Health Clinical K.K., Nippon Kayaku Co.,Ltd., EP-CRSU Co., Ltd., Mebix, Inc., Bristol Myers Squibb K.K., Janssen Pharmaceutical K.K., Eisai Co., Ltd., AstraZeneca K.K., Mochida Pharmaceutical Co., Ltd., Covance Japan Inc., Japan linical Research Operations, Takeda Pharmaceutical Co.,Ltd., GlaxoSmithKline K.K., Sanofi K.K., Chugai Pharmaceutical Co.,Ltd., Nippon Boehringer Ingelheim Co.,Ltd., Sysmex Corporation, Medical Reserch Support, Eli Lilly Japan K.K., Amgen Inc., Novartis Pharma K.K., Novartis Pharma K.K., Srl, Inc. T. Mitsudomi Financial Interests, Personal, Invited Speaker AstraZeneca, Chugai, Novartis, MSD, Bristol Myers Squibb, Ono, Pfizer, Eli Lilly, Merck Biopharma;Financial Interests, Personal, Advisory Board AstraZeneca, Boehringer Ingelheim, Chugai, Novartis, MSD, Bristol Myers Squibb, Ono, Pfizer, Amgen, Janssen, Takeda, Eli-Lilly;Financial Interests, Institutional, Invited Speaker Boehringer Ingelheim, AstraZeneca, Chugai, MSD, Taiho, Daiichi Sankyo, Ono;Non-Financial Interests, Personal, Leadership Role Interanational Association for Study of Lung Cancer. All other authors have declared no conflicts of interest. Copyright © 2022 European Society for Medical Oncology