Combining immunotherapy with Trop2 ADc in early stage non-small cell lung cancer (CITADEL)

BackgroundPerioperative pembrolizumab plus chemotherapy improved pathological complete response (pCR) rate, event-free survival (EFS) and overall survival (OS) compared to neoadjuvant chemotherapy alone in patients with resectable stage II - III non-small cell lung cancer (NSCLC) (KEYNOTE-671 study) and is now established as the new standard of care. The combination of pembrolizumab with sacituzumab govitecan, a TROP2-directed antibody drug conjugate, demonstrated high antitumour efficacy as first-line treatment for metastatic NSCLC (EVOKE-02 study). We hypothesize that perioperative pembrolizumab plus sacituzumab govitecan can further improve survival outcomes in patients with resectable stage II - III NSCLC.Trial designCITADEL (Combining Immunotherapy with Trop2 ADc in Early stage non-small cell Lung cancer) is an investigator-initiated, open-label, single arm, multicentre phase II study investigating the efficacy of perioperative pembrolizumab plus sacituzumab govitecan in patients with resectable stage II - III (AJCC 8th edition) NSCLC without EGFR/ALK alterations. Eligible patients will receive 4 cycles of neoadjuvant pembrolizumab (200mg every 3 weeks) and sacituzumab govitecan (10mg/kg on day 1 and 8 every 3 weeks). Surgical resection will be performed 4-8 weeks after the 4th cycle of study treatment. Afterwards, patients will receive 13 more cycles of pembrolizumab. The primary endpoint is pCR rate in the intention-to-treat population. Key secondary endpoints include 1-year and 2-year EFS, OS, surgical resection rate, safety outcomes, and patient reported quality of life assessment. Exploratory endpoints include plasma and tumour biomarkers predictive of pathological response. We hypothesize that the study treatment will increase pCR rate from 18% in landmark KEYNOTE-671 study (perioperative pembrolizumab plus chemotherapy) to 38%. Assuming one sided alpha of 5%, a power of 80%, and 5% dropout rate, 37 subjects will be enrolled. This trial has started enrolment in Feb 2024.Clinical trial identificationNCT number: NCT06055465.Legal entity responsible for the studyThe Chinese University of Hong Kong.FundingGilead Science, Merck Sharp & Dohme (ASIA) Ltd.DisclosureS.C.M. Li: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Novartis, Amgen, Pfizer, Takeda, ACEOncology, Gilead, Guardant Health, Janssen, Merck, MSD, BMS; Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Amgen, AnHeart Therapeutics, Takeda, Yuhan, BlossomHill Therapeutics. T.S.K. Mok: Financial Interests, Personal, Invited Speaker: ACEA Pharma, AbbVie, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Daz Group, Eli Lilly, Fishawack Facilitate, InMed Medical Communication, Janssen Pharmaceutical NV, Jiahui Holdings Co., LiangYiHui Healthcare, Lucence Health Inc., Lunit USA, Inc., MD Health, MSD, Medscape/WebMD, Merck Pharmaceuticals HK Ltd, Merck Serono, MiRXES, Novartis, OrigiMed Co. Ltd., PER, PeerVoice, Permanyer SL, Pfizer, Prime Oncology, Research to Practice, Roche, Sanofi-Aventis, Shanghai BeBirds Translation & Consulting Co., Ltd., Shanghai Promedican Pharmaceuticals Co., Ltd, Taiho Pharmaceutical Co., Ltd, Takeda, Touch Medical Media; Financial Interests, Personal, Advisory Board: ACEA Pharma, AbbVie, Alpha Biopharma, Amgen, Amoy Diagnostics, Bayer Healthcare Pharmaceuticals Ltd., BeiGene, BerGenBio ASA, Berry Oncology, Berry Oncology, Blueprint Medicines, Boehringer Ingelheim, Bowtie Life Insurance Co Ltd, Bristol Myers Squibb, C4 Therapeutics, CStone Pharma, Cirina Ltd., Covidien LP, Curio Science, D3 Bio Ltd., Da Volterrra, Daiichi Sankyo, Eisai, Eli Lilly, F. Hoffmann-La Roche Ltd / Genentech, Fishawack Facilitate, G1 Therapeutics, Gilead Sciences, Gritstone Oncology, Guardant Health, Hengrui, IQVIA, Ignyta, Imagene AI Ltd, Incyte Corporation, Inivata, Janssen, Lakeshore Biotech, Loxo Oncology, Lucence Health Inc., Lunit USA, Inc., MSD, Medscape LLC / WebMD, Merck Serono, MiRXES, Mirati Therapeutics, MoreHealth, Novartis, OSE Immunotherapeutics, OrigiMed, Pfizer, Prenetics Global Limited, Puma Tech., Qiming Dev., Regeneron Pharmaceuticals Inc., Roche, SFJ Pharmaceutical Ltd., Sanofi-Aventis, Simcere Zaiming, Inc, Simcere of America Inc, Synergy Research, Takeda, Tigermed, Vertex Pharmaceuticals, Virtus Medical, Yuhan Corporation; Financial Interests, Personal, Other, consultation services: AVEO Pharmaceuticals, Inc, Alentis Therapeutics AG, BerGenBio ASA, Bridge Biotherapeutics Inc, Elevation Oncology, GLG’s Healthcare, Genentech, Illumina, Inc., Novocure GmbH, Phanes Therapeutics, geneDecode Co., Ltd; Financial Interests, Personal, Other, Consultation services: Adagene, XENCOR, Inc; Financial Interests, Personal, Other, Consultation Services: HiberCell, Inc., Seagen International GmbH, AnHeart Therapeutics Inc; Financial Interests, Personal, Other, Consultant Services: Schrödinger, Inc; Financial Interests, Personal, Member of Board of Directors: AstraZeneca, Aurora, Insighta; Financial Interests, Personal, Member of Board of Directors, Former known as Hutchison Chi-Med: HutchMed; Financial Interests, Personal, Stocks/Shares, Former known as Hutchison Chi-Med: HutchMed; Financial Interests, Personal, Stocks/Shares: Biolidics Ltd., Aurora Tele-Oncology, AstraZeneca, D3 Bio, Lunit Inc., Precentics, Alentis Therapeutics AG; Financial Interests, Institutional, Funding, For clinical trials performed at CUHK: AstraZeneca, BMS, Merck Serono, MSD, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, XCovery, Takeda, G1 Therapeutics, Clovis Oncology; Non-Financial Interests, Advisory Role: geneDecode; Non-Financial Interests, Other, Invited Speaker: AstraZeneca, Aurora Tele-Oncology, Lunit USA, Inc.; Non-Financial Interests, Leadership Role, Term ended: Chinese Society of Clinical Oncology (CSCO); Non-Financial Interests, Leadership Role, Term ended on 30 June 2022: American Society of Clinical Oncology (ASCO); Non-Financial Interests, Leadership Role: Asian Thoracic Oncology Research Group (ATORG), Chinese Lung Cancer Research Foundation Limited (CLCRF), Hong Kong Cancer Fund (HKCF), Hong Kong Cancer Therapy Society (HKCTS), St. Stephen’s College & Prep. School (Hong Kong); Non-Financial Interests, Leadership Role, Term ended on 30 April 2019: International Association for the Study of Lung Cancer (IASLC); Non-Financial Interests, Leadership Role, Honorary Secretary, from Dec 2022 - Present: Hong Kong Academy of Sciences. V.H.F. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Roche, Merck Sharp & Dohme, Boston Scientific, Takeda, ZaiLab; Financial Interests, Institutional, Research Grant: AstraZeneca, Boston Scientific. All other authors have declared no conflicts of interest.