海报库PosterKeep
PO.CTP01.03 · 进行中的临床试验

EIK1001（一种TLR7/8双重激动剂）联合帕博利珠单抗作为晚期黑色素瘤参与者一线治疗的自适应2/3期研究（Teluride-006）

Adaptive phase 2/3 study of EIK1001, a TLR7/8 dual agonist, in combination with pembrolizumab, as first-line therapy in participants with advanced melanoma (Teluride-006)

编号 CT224 展板 19 时间 4/21 09:00–12:00 区域 Section 51 主讲 Diwakar Davar
分会场 Phase II and Phase III Clinical Trials in Progress
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作者与单位 Authors & Affiliations

Diwakar Davar1, Bernardo Rapoport2, Jan C. Simon3, Oliver Bechter4, Stephane Dalle5, Yin Wu6, Daniel Brungs7, Anna Maria Di Giacomo8, Hanna Eriksson9, Peter Mohr10, Rossanna Pezo11, Egle Ramelyte12, Gareth Rivalland13, Toshifumi Hoki14, Geetha Krishna Kaza15, Yayan Zhang15, Etah Kurland15, Alexander Eggermont16

1University of Pittsburgh Medical Center (UPMC)- Hillman Cancer Center, Pittsburg, PA,2The Clinical and Translational Research Unit of the Medical Oncology Centre of Rosebank, Saxonwold, Johannesburg, South Africa; Department of Immunology, Faculty of Health Sciences, University of Pretoria, Prinshof, South Africa,3Universität Leipzig, Leipzig, Germany,4Universitaire Ziekenhuizen Leuven (UZ Leuven), Leuven, Belgium,5Lyon Sud, Oullins-Pierre-Bénite, France,6Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom,7Cancer Care Wollongong, Wollongong, NSW, Australia,8University of Siena and Center for Immuno-oncology, Siena, Italy,9Karolinska University Hospital, Stockholm, Sweden,10lbe Kliniken Stade-Buxtehude, Stade, Germany,11Sunnybrook Research Institute, North York, ON, Canada,12University Hospital of Zürich, Zürich, Switzerland,13Auckland City Hospital, Auckland, New Zealand,14Merck & Co., Inc., Rahway, NJ,15Eikon Therapeutics, Jersey City, NJ,16UMC Utrecht & Princess Maxima Center, Utrecht, Netherlands; Comprehensive Cancer Center Munich of the Technical University Munich and the Ludwig Maximilians University, Munich, Germany

摘要 Abstract

中文摘要
背景：免疫检查点抑制剂（ICI），包括抗PD-1抗体，可逆转肿瘤诱导的免疫抑制并促进有效的抗肿瘤T细胞应答。它们大幅改善了晚期黑色素瘤治疗的结局，在无进展生存（PFS）和总生存（OS）方面带来了持久改善。虽然在抗PD-1的基础上加入抗CTLA-4或抗LAG-3可增强疗效，但这些方法并未直接靶向肿瘤微环境中占主导地位的髓系介导的耐药机制，因此需要靶向该轴的新药。EIK1001是一种TLR7/8双重激动剂，可激活髓系和浆细胞样树突状细胞，以刺激先天炎症和适应性免疫。在多项研究中，EIK1001耐受性良好，并在单药治疗以及与ICI联合治疗中均显示出临床活性。 方法：TeLuRide-006（NCT#06697301）是一项全球性、多中心、随机、双盲、自适应的2/3期试验，评估EIK1001或安慰剂联合帕博利珠单抗（pembro）作为晚期皮肤黑色素瘤参与者（pts）的一线治疗。约740例患者将被随机分组，包括一个剂量优化（DO）阶段，其中患者按1:1:1随机分配至两个EIK1001剂量水平或安慰剂，各自与pembro联合给药，随后进入2/3期扩展，评估所选EIK1001剂量对比安慰剂（均与pembro联合）。中期分析将指导从DO推进至2期，并随后推进至3期。EIK1001或安慰剂静脉给药，每周一次（QW）直至第27周结束，然后每3周一次（Q3W）；而pembro每3周一次（Q3W）静脉给药。患者按既往抗PD-1辅助治疗、LDH水平和BRAF突变状态进行分层。关键入选标准包括年龄≥12岁的患者（存在国家特定差异）、预期寿命≥3个月、不可切除的III期或IV期黑色素瘤、已知的BRAF V600状态、至少一个RECIST v1.1可测量病灶，以及既往或现在无肺炎/间质性肺病。主要目的是评估两种EIK1001剂量与pembro联用在DO中的疗效和安全性，并比较所选EIK1001剂量对比安慰剂（与pembro联用）之间的PFS（由盲态独立中心审查[BICR]依据RECIST v1.1评估）和OS。次要目的包括任一EIK1001剂量与pembro联用的安全性和耐受性、由BICR依据RECIST v1.1评估的客观缓解率和缓解持续时间。探索性目的包括缓解时间、EIK1001暴露-反应关系和健康相关生活质量。该研究于2025年5月21日入组（随机分配）首例参与者，截至摘要提交时已在22个国家的89个中心启动。
查看英文原文 English abstract
BACKGROUND : Immune checkpoint inhibitors (ICIs), including anti-PD-1 antibodies, reverse tumor-induced immune suppression and promote effective anti-tumor T-cell responses. They have drastically improved outcome in advanced melanoma therapy, yielding durable improvements in progression-free survival (PFS) and overall survival (OS). Although adding anti-CTLA-4 or anti-LAG-3 enhances efficacy beyond anti-PD-1 alone, these approaches do not directly target dominant myeloid-mediated resistance mechanisms within the tumor microenvironment, and new agents targeting this axis are needed. EIK1001, a TLR7/8 dual-agonist, activates myeloid and plasmacytoid dendritic cells to stimulate innate inflammation and adaptive immunity. Across multiple studies, EIK1001 has been well tolerated and has demonstrated clinical activity both as monotherapy and in combination with ICIs. METHODS : TeLuRide-006 (NCT#06697301) is a global, multicenter, randomized, double-blind, adaptive Phase 2/3 trial of EIK1001 or placebo, in combination with pembrolizumab (pembro), as first-line therapy for participants (pts) with advanced cutaneous melanoma. Approximately 740 pts will be randomized, including a dose-optimization (DO) stage in which pts are randomized 1:1:1 to two EIK1001 dose levels or placebo, each administered with pembro, followed by Phase 2/3 expansion evaluating the selected EIK1001 dose versus placebo, with pembro. Interim analyses will guide progression from DO to Phase 2 and subsequently to Phase 3. EIK1001 or placebo is administered IV QW until the end of Week 27 then Q3W; while pembro is administered IV Q3W. Pts are stratified by prior anti-PD-1 adjuvant therapy, LDH level, and BRAF mutational status. Key eligibility criteria include patients ≥12 years (with country-specific variations), life expectancy ≥3 months, unresectable Stage III or Stage IV melanoma, known BRAF V600 status, at least one RECIST v1.1-measurable lesion, and no prior or current pneumonitis/interstitial lung disease. Primary objectives are to assess the efficacy and safety of two EIK1001 doses with pembro in DO, and to compare PFS (RECIST v1.1 by blinded independent central review [BICR]) and OS between the selected EIK1001 dose and placebo in combination with pembro. Secondary objectives include safety and tolerability of either EIK1001 dose with pembro, objective response rate and duration of response per RECIST v1.1 by BICR. Exploratory objectives include time to response, EIK1001 exposure-response relationships, and health-related quality of life. This study enrolled (randomized) its first participant on 5/21/2025 and is activated at 89 sites in 22 countries at the time of abstract submission.
利益披露 Disclosure
D. Davar, Arcamyra; mBiomics; Pienomial; Zola Stock. ACM Bio; Ascendis; Castle; Clinical Care Options (CCO); Gerson Lehrman Group (GLG); Immunitas; Medical Learning Group (MLG); Regeneron; Replimmune; Trisalus; Xilio Therapeutics Other, Consultancy. Castle Biosciences; Regeneron Other, Speaker's Bureau. Arcus; Immunocore; Merck; Regeneron Pharmaceuticals Inc; Tesaro/GSK Other, Research funding. Individual patents: US Patent 63/124,231; US Patent 63/208,719 Patent, Other, Individual Patents. B. Rapoport, None. J. C. Simon, Novartis; Lilly; Incyte; Johnson & Johnson; Almirall Other, Consultancy. Abbvie; Almirall Travel. O. Bechter, Pierre Fabre Other, Institutional Consultancy. S. Dalle, BMS; MSD; Pierre Fabre Other, Research funding. BMS; MSD; Regeneron Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events. BMS; MSD Travel, Other, Support for attending meetings and/or travel. Trim 24 patent in melanoma patent Patent. BMS; MSD Other, Participation on a Data Safety Monitoring Board or Advisory Board. Sanofi Other, Spouse is Sanofi employee and has stock options. Y. Wu, Sun Pharma; Bristol Meyers Squibb (BMS) Other, Honoraria. E15 VC; Boxer Capital Management Other, Consulting. D. Brungs, MSD; AstraZeneca; Medisun Other, Honoraria. AstraZeneca Other, Consultancy. A. Di Giacomo, BMS; MSD; Pierre Fabre; Sanofi; Immuncore Other, Consulting. Pierre Fabre Travel. H. Eriksson, Johnson & Johnson Other, Honoraria. Novartis; BMS; Pierre Fabre Other, Compensation to the clinic or institution. BMS; Pierre Fabre; Immunocore Other, Consultancy to the clinic. P. Mohr, Baiersdorf; BMS; MSD; Novartis; Merck Serono; Replimune; SUN Pharma; Sanofi/Regeneron; Pierre Fabre; Immunocore; Incyte; Delcath Other, Honoraria for lectures/advisory boards. BMS; Novartis; MSD Other, Research funding. SUN Pharma; Pierre Fabre Other, Congress participation support. R. Pezo, Pfizer; Gilead; Merck Other, Honoraria. Pfizer; Merck; Novartis; BMS; AstraZeneca; Sanofi; Regeneron; Gilead Other, Consultancy. Eikon Therapeutics; Merck; Pfizer; Novartis Other, Research funding. E. Ramelyte, Amgen; Sanofi/Regeneron; Sun Pharma Other, Research Funding for Institution. Amgen, Sanofi, Pierre Fabre Travel, Other, Accommodations, Expenses. BMS GmbH & Co. KG; Galderma; Lilly; MSD; Pierre Fabre; Sanofi; Regeneron Other, Honoraria. Amgen; Kyowa Kirin International; Sanofi/Regeneron; Pierre Fabre Other, Consultancy or Advisory Role. BMS GmbH & Co. KG; MSD; Sanofi/Regeneron; Delcath Other, Speakers' Bureau. Contribution to UpToDate chapter update for Superficial acitic porokeratosis. Patent, Other Intellectual Property, Other, Royalties. Novo Nordisk; Lilly Stock, Other, Ownership Interests. G. Rivalland, Harbour Cancer and Wellness Employment. Harbour Cancer and Wellness g., Board of Directors, non-salaried role). AstraZeneca Other, Consultancy. Roche Travel. T. Hoki, Merck & Co., Inc. Employment. Merck & Co., Inc. Stock. G. Kaza, Eikon Therapeutics Employment, Stock. Y. Zhang, Eikon Therapeutics Employment, Stock. E. Kurland, Eikon Therapeutics Employment, Stock. A. Eggermont, Sairopa BV Other, Leadership: CMO. Sairopa BV; SkylineDX BV Stock Option. IO BIOTECH Stock. Agenus;Boehringer Ingelheim GmbH; BioInvent; BioNTech; Brenus; CatalYm; Egle; Eurobio; Imcheck; Immatics; IO Biotech; Merck&Co/MSD; Oncolytics; Pfizer; Pierre Fabre Other, Honoraria. QBiotics; Regeneron; Sairopa BV; Secaarna; SkylineDX; Thermosome GmbH; Trained Immunity TX Discovery Other, Honoraria. Agenus; Boehringer Ingelheim GmbH; BioInvent; BioNTech; Brenus; CatalYm; Egle; Eurobio; Imcheck; Immatics; IO Biotech; Merck&Co/MSD; Oncolytics; Pfizer; Pierre Fabre; QBiotics; Regeneron; Sairopa BV Other, Consultancy. Secaarna; SkylineDX; Thermosome GmbH; Trained Immunity TX Discovery Other, Consultancy.

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