PO.CT01.04 · 临床试验

IOB-032/PN-E40：一项新辅助/辅助IO102-IO103癌症疫苗联合pembrolizumab治疗可切除HNSCC的2期研究

IOB-032/PN-E40: A phase 2 study of neoadjuvant/adjuvant IO102-IO103 cancer vaccine plus pembrolizumab in resectable HNSCC

编号 CT240 展板 5 时间 4/21 02:00–05:00 区域 Section 50 主讲 Barbara Burtness, MD

分会场 Phase II Clinical Trials

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作者与单位 Authors & Affiliations

Barbara Burtness¹, Ravindra Uppaluri², Michael J. Dennis³, Annette M. Lim⁴, Richard A. Scolyer⁵, Erin Alesi⁶, Ayako Wakatsuki Pedersen⁷, Amy Wesa⁷, Ravi K. Adapala⁷, Ulla Kring Hansen⁷, Marcos Iglesias⁷, Bushi Wang⁷, Cecilie Abildgaard⁷, Qasim Ahmad⁷, Francois Ringeisen⁷, Georgina V. Long⁸, Robert I. Haddad⁹

¹Yale School of Medicine and Yale Cancer Center, New Haven, CT,²Brigham and Women's Hospital, Harvard Medical School, Boston, MA,³Center for Head and Neck Oncology, Dana-Farber Cancer Institute, Boston, MA,⁴Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Australia,⁵The University of Sydney, Royal Prince Alfred Hospital and NSW Health Pathology, Sydney, Australia,⁶VCU Massey Comprehensive Cancer Center, Richmond, VA,⁷IO Biotech, Copenhagen, Denmark,⁸Melanoma Institute Australia, The University of Sydney, Royal North Shore & Mater Hospitals, Sydney, Australia,⁹Dana-Farber Cancer Institute, Boston, MA

摘要 Abstract

中文摘要

IO102-IO103是一种在研的免疫调节性治疗性癌症疫苗，通过激活并扩增针对IDO1和PD-L1阳性细胞的T细胞，靶向肿瘤微环境（TME）中的肿瘤细胞和免疫抑制细胞。围手术期给予pembrolizumab（pembro）已证明可显著改善可切除头颈部鳞状细胞癌（HNSCC）患者（pts）的无事件生存期（EFS）。本文测试IO102-IO103联合pembro在围手术期的应用。IOB-032/PN-E40（NCT05280314）是一项开放标签、多队列、2期试验，评估IO102-IO103联合pembro作为新辅助/辅助治疗的安全性、抗肿瘤和免疫活性。可切除HNSCC（III—IV期）患者，无论人乳头瘤病毒（HPV）状态如何，每3周（Q3W）接受IO102-IO103和pembro，共2或3个周期，随后进行手术和基于风险的标准放疗（RT）±化疗（chemo）。恢复后，IO102-IO103联合pembro辅助治疗Q3W给药，最多15个周期。主要终点为手术时的主要病理缓解（MPR；残余存活肿瘤[RVT]≤10%）。其他关键终点包括：EFS、安全性和疫苗特异性免疫应答。2023年12月至2024年11月期间，共入组16例可切除HNSCC患者（包括2例HPV阴性口咽癌）。所有患者均完成至少2个周期的新辅助治疗。截至2025年7月18日数据截止时，13例（81.3%）患者已接受手术，可进行中心确定的病理缓解评估。从首次新辅助给药至手术的中位时间为34天（范围29—134）。1例患者拒绝手术但希望继续治疗；1例患者进展且无法手术，1例患者在手术前撤回同意。在13例可评估患者中，经中心审查3例（23.1%）达到病理缓解（RVT≤50%，pTR-2），经研究者审查5例（38.5%）达到病理缓解；两种评估均判定1例（7.7%）患者符合MPR标准（≤10%）。截至数据截止时，11例（68.8%）患者在RT±chemo后接受了辅助治疗，其中4例接受了放化疗。2例患者决定不启动辅助治疗。总计3例（18.8%）患者因不良事件停止治疗；其中2例为治疗相关（软组织水肿，3级；注射部位肿块，1级）。EFS以及治疗相关TME变化的分析将与包括PD-L1状态在内的基线特征一并呈现。这是首个研究IDO1-PD-L1免疫调节性癌症疫苗联合抗PD-1治疗作为HNSCC围手术期治疗的试验。该方案耐受性良好，新辅助给药和病理评估的实施是可行的。进一步随访将为在围手术期pembro治疗中加入IO102-IO103的潜在获益提供关键见解。

查看英文原文 English abstract

IO102-IO103 is an investigational immune-modulatory therapeutic cancer vaccine targeting tumor and immune-suppressive cells in the tumor microenvironment (TME) via activation and expansion of T cells against IDO1 and PD-L1-positive cells. Perioperative administration of pembrolizumab (pembro) has demonstrated significant improvement in event-free survival (EFS) for patients (pts) with resectable head and neck squamous cell carcinoma (HNSCC). Here we test IO102-IO103 plus pembro in the perioperative setting. IOB-032/PN-E40 (NCT05280314) is an open-label, multi-cohort, Phase 2 trial evaluating safety, anti-tumor and immunological activity of IO102-IO103 plus pembro as neoadjuvant/adjuvant treatment. Pts with resectable HNSCC (stage III−IV), regardless of human papillomavirus (HPV) status, received IO102-IO103 and pembro every 3 weeks (Q3W) for 2 or 3 cycles followed by surgery and risk-based standard of care radiotherapy (RT) ± chemotherapy (chemo). After recovery, adjuvant treatment with IO102‑IO103 plus pembro was administered Q3W for up to 15 cycles. The primary endpoint is major pathological response (MPR; ≤10% residual viable tumor [RVT]) at surgery. Other key endpoints include: EFS, safety and vaccine-specific immune-responses. Between Dec 2023 and Nov 2024, 16 pts with resectable HNSCC (including 2 HPV- oropharyngeal carcinoma) were enrolled. All pts completed at least 2 cycles of neoadjuvant treatment. At data cutoff 18-Jul-2025, 13 (81.3%) pts had undergone surgery and were evaluable for centrally determined pathological response. Median time to surgery was 34 days (range 29−134) from the first neoadjuvant dose. One pt refused surgery but wished to stay on treatment; 1 pt progressed and became inoperable, and 1 pt withdrew consent prior to surgery. Of 13 evaluable pts, 3 (23.1%) had a pathological response with ≤50% RVT (pTR-2) by central review and 5 (38.5%) had a pathological response per investigator review; both assessed 1 (7.7%) pt as meeting the criteria for MPR (≤10%). At data cutoff, 11 (68.8%) pts received adjuvant therapy after RT ± chemo, 4 of whom received chemoRT. Two pts decided not to initiate adjuvant treatment. In total, 3 (18.8%) pts discontinued treatment due to adverse events; two of these were treatment-related (soft tissue edema, grade 3; injection-site lump, grade 1). EFS and analysis of treatment-associated changes in the TME will be presented, together with baseline characteristics including PD-L1 status. This is the first trial investigating an IDO1-PD-L1-immune-modulatory cancer vaccine plus anti-PD-1 therapy as perioperative treatment for HNSCC. The regimen was well-tolerated, and the implementation of neoadjuvant dosing and pathological assessment was feasible. Further follow-up will provide key insights into the potential benefit of adding IO102-IO103 to perioperative treatment with pembro.

利益披露 Disclosure

B. Burtness, ALX Oncology, AstraZeneca, Clearview Health Partners, Coherus Biosciences Inc., Genentech, Genmab, IO Biotech, One Carbon, Pfizer, Rakuten, Takeda Pharmaceuticals Other, Consultant. Answers in CME Other, Other. Clinical Care Options LLC Other, Speaker. GlaxoSmithKline Other, Consultant fees and research fees to self and institution. Induxion Other, Consultant fees to self and institution. Janssen Pharmaceuticals Other, Consultant fees and research fees to self and institution. MedLearning Group Other, Speakers bureau or promotional education. Merck and Merck KGaA Other, Consultant fees and research fees to self and institution. Merus Other, Data & Safety Monitoring. OncLive Other, Other. PRIME Other, Speakers bureau or promotional education. Up to Date Other, Other. Yale School of Medicine Employment. R. Uppaluri, Merck Other, Travel, Consulting or Advisory Role. Daichi-Sankyo Other, Research funding and consulting or Advisory Role. Regeneron Consulting or Advisory Role. Johnson & Johnson/Janssen Consulting or Advisory Role. Washington University Other Intellectual Property, Washington University licenses mouse oral cancer cell lines made by my lab. I receive royalties from Washington University from these agreements . IO Biotech Uncompensated Relationships. M. J. Dennis, None. A. M. Lim, Pfizer uncompensated consultancy. Eisai uncompensated consultancy. Lilly uncompensated consultancy. Merck Healthcare uncompensated consultancy. Regeneron Pharmaceuticals Other, conference registration and support for an investigator initiated trial and translational research support from Regeneron Pharmaceuticals received by the institution. Peter MacCallum Cancer Center Discovery Partner Fellowship Other, Supported. R. A. Scolyer, Pfizer Other, uncompensated consultancy. Eisai Other, uncompensated consultancy. Lilly Other, uncompensated consultancy. Merck Healthcare Other, uncompensated consultancy. Regeneron Pharmaceuticals Other, support for an investigator initiated trial and translational research support from Regeneron Pharmaceuticals received by the institution. Peter MacCallum Cancer Center Discovery Partner Fellowship Other, supported. E. Alesi, None. A. Wakatsuki Pedersen, IO Biotech Employment, Stock. A. Wesa, IO Biotech Employment, Stock. R. K. Adapala, IO Biotech Employment, Stock. U. Kring Hansen, IO Biotech Employment, Stock. M. Iglesias, IO Biotech Employment, Stock. B. Wang, IO Biotech Employment, Stock. C. Abildgaard, IO Biotech Employment, Stock. Q. Ahmad, IO Biotech Employment, Stock. F. Ringeisen, IO Biotech Employment, Stock. G. V. Long, Bayer Other, consultant advisor. BioNTech Other, consultant advisor. Boehringer Ingelheim Other, consultant advisor. Bristol Myers Squibb Other, consultant advisor. Byondis B.V. Other, consultant advisor. Evaxion Other, consultant advisor. Fortiva Biologics Other, consultant advisor. GI Innovation Other, consultant advisor. Hexal AG (Sandoz Company) Other, consultant advisor. Highlight Therapeutics S.L. Other, consultant advisor. Immunocore Other, consultant advisor. Innovent Biologics USA Other, consultant advisor. IO Biotech Other, consultant advisor. Iovance Biotherapeutics Other, consultant advisor. MSD Other, consultant advisor. Novartis Other, consultant advisor. Pierre Fabre Other, consultant advisor. Regeneron Other, consultant advisor. Scancell Other, consultant advisor. SkylineDX B.V. and Strand therapeutics Other, consultant advisor. R. I. Haddad, Dana-Farber Cancer Institute Employment. NCCN Other, leadership. tosk Stock. Merck, Eisai, AstraZeneca, GSK, EMD Serono, Bayer, Boehringer Ingelheim, ALX Oncology, aveo, Genmab, PDS Biotechnology, Scholar Rock, Genzyme, Johnson & Johnson/Janssen, RAPT Therapeutics, Abbvie Other, Consulting or Advisory Role. Bristol-Myers Squibb/Celgene Consulting or Advisory Role. Merck, Bristol-Myers Squibb, AstraZeneca, Genentech, Pfizer, Kura, EMD Serono, Incyte, Merus, AVEO, GlaxoSmithKline Other, Research funding for institution. Nanobiotix, ISA Pharmaceuticals, Boehringer Ingelheim, Hookipa Pharma, Incyte Other, Other relationship.

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