Phase II Study of Neoadjuvant Concurrent Chemo-immuno-radiation Therapy Followed by Surgery and Adjuvant Immunotherapy for Resectable Stage IIIA-B (Discrete N2) Non-small-cell Lung Cancer: SQUAT trial (WJOG 12119L).

Introduction: We describe our ongoing 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 (discrete N2) non-small-cell lung cancer (NSCLC) (registered at the Japan Pharmaceutical Information Center, Clinical Trials Information-195069).
Patients and Methods: Key inclusion criteria include (1) clinical T1-3/T4 (tumor size) N2 stage IIIA-B NSCLC, and (2) pathologically confirmed N2 without extranodal invasion (based on diagnostic imaging). Patients will receive concurrent chemoradiotherapy (carboplatin [area under the curve = 2] and paclitaxel [40 mg/m ² ] on days 1, 8, 15, 22, and 29, with involved-field radiation therapy [RT] [dose 50 Gy] on days 1-25) and neoadjuvant immunotherapy (durvalumab [1500 mg] on days 1 and 29). Surgical resection with mediastinal lymph node dissection is performed within 2 to 6 weeks after RT. Consolidation therapy with durvalumab is administered for up to 1 year after surgery. The primary endpoint is major pathologic response (MPR) (≤10% residual viable tumor) according to the central pathological assessment. Secondary endpoints are progression-free survival, overall survival, and safety. The sample size is planned to be 31 patients based on the exact binomial distribution with a 1-sided significance level of 5% and a power of 80%, and assuming a threshold MPR rate of 40% and an expected MPR rate of 65%.
Conclusion: This trial will help establish a novel treatment strategy for resectable N2-positive NSCLC.
Competing Interests: Akira Hamada has received grants and personal fees from AstraZeneca, personal fees from Chugai, and grants from the Japan Society for the Promotion of Science. Junichi Soh has received grants from AstraZeneca, and grants from the Japan Society for the Promotion of Science. Akito Hata has received grants and personal fees from AstraZeneca, Eli Lilly, and Boehringer Ingelheim, personal fees from Chugai, and grants from MSD. Kiyoshi Nakamatsu has received grants from AstraZeneca. Yasushi Yatabe has received grants and personal fees from AstraZeneca, personal fees from MSD, Chugai-pharma, Pfizer, Roche/Ventana, Agilent/Dako, Thermo Fisher Science, ArcherCD, Novartis, Elli-Lily, and Daiichi Sankyo. Hiroyuki Oizumi has received grants from AstraZeneca and ONO Pharmaceutical Co., Ltd. Masahiro Tsuboi has received grants and personal fees from AstraZeneca, ONO Pharmaceutical Co., Ltd., Bristol-Myers Squibb KK, Eli Lilly Japan, MSD, and Novartis, and personal fees from Johnson and Johnson Japan, Chugai Pharmaceutical Co., Ltd., Teijin Pharma, Taiho Pharma, Medtronic Japan, and grants from Beohringer-Ingelheim Japan. Hidehito Horinouchi has received grants and personal fees from AstraZeneca, BMS, ONO, MSD, Janssen, and Chugai, personal fees from Lilly, Merck Biophama, Kyowa-Kirin, and Nihonkayaku, and grants from Daiichi-Sankyo, Abbvie, and Genomic Health. Ichiro Yoshino has received grants and personal fees from AstraZeneca. Masayuki Tanahashi has received grants from AstraZeneca. Shinichi Toyooka has received grants from AstraZeneca, Illumina, Eurofins, and Eli Lilly, grants and personal fees from Taiho, Kyorin, and Chugai, and personal fees from ONO, Daiichi-Sankyo, Medtronic, Johnson and Johnson. Morihito Okada has received grants and personal fees from AstraZeneca. Hiroyasu Yokomise has received grants from AstraZeneca. Motohiro Yamashita has received grants from AstraZeneca. Yasumasa Nishimura has received grants from AstraZeneca. Nobuyuki Yamamoto has received grants and personal fees from 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., Boehringer-Ingelheim, Novartis, and Pfizer Inc., personal fees from Thermo Fisher Scientific, Bristol-Myers Squibb, Life Technologies Japan Ltd., Nippon Kayaku, and Merk Biopharma, and grants from Astellas Pharma Inc., Tsumura & Co., Shionogi Co., Ltd., AbbVie GK., Amgen Inc., Kyorin Pharmaceutical Co., Ltd., Eisai Co., Ltd., Terumo Corporation, Toppan Printing Co., Ltd., and Tosoh. Kazuhiko Nakagawa has received grants and personal fees from AstraZeneca K.K., Astellas Pharma Inc., MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., Bristol Myers Squibb Company, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Merck Serono Co., Ltd./Merck Biopharma Co., Ltd., Taiho Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Limited, and AbbVie Inc, grants, personal fees, and other from Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Eli Lilly Japan K.K., and Takeda Pharmaceutical Co., Ltd., personal fees from Clinical Trial Co., Ltd., Medicus Shuppan, Publishers Co., Ltd., Care Net, Inc., Reno, Medical K.K., Medical Review Co., Ltd., Roche Diagnostics K.K., Bayer Yakuhin, Ltd., Medical Mobile Communications Co., Ltd., 3H Clinical Trial Inc., Nichi-Iko Pharmaceutical Co., Ltd., Nanzando Co., Ltd., Yodosha Co., Ltd., Nikkei Business Publications, Inc., Thermo Fisher Scientific K.K., Yomiuri Telecasting Corporation, and Nippon Kayaku Co., Ltd., personal fees and other from Kyorin Pharmaceutical Co., Ltd., and grants from inVentiv Health Japan, ICON Japan K.K., Gritsone Oncology, Inc., Parexel International Corp., Kissei Pharmaceutical Co., Ltd., EPS Corporation, Syneos Health, Pfizer R&D Japan G.K., A2 Healthcare Corp., Quintiles Inc./IQVIA Services Japan K.K., EP-CRSU Co., Ltd., Linical Co., Ltd., Eisai Co., Ltd., CMIC Shift Zero K.K., Kyowa Hakko Kirin Co., Ltd, Bayer Yakuhin, Ltd., EPS International Co., Ltd., and Otsuka Pharmaceutical Co., Ltd. Tetsuya Mitsudomi has received grants and personal fees from AstraZeneca, Boehringer Ingelheim, and Chugai, personal fees from Bristol-Myers Squibb, Eli Lilly, Merck Sharp and Dohme, and Pfizer, grants from Daiichi Sankyo, Taiho, Ono Pharmaceutical, and the Japan Society for the Promotion of Science, and other from Novartis. The other authors have stated that they have no conflict of interest.
(Copyright © 2021. Published by Elsevier Inc.)