ICT-01

本期看点1. Genmab公司旗下抗体偶联药物（ADC）rinatabart sesutecan用以治疗复发性/晚期子宫内膜癌的早期临床试验结果积极，低剂量组患者的疾病控制率（DCR）达100%。2. γ9δ2 T细胞激活剂ICT01联用阿扎胞苷和维奈托克（Aza-Ven）治疗不适合强化化疗的新确诊的急性髓系白血病（AML）患者，在一项1/2期临床试验中的复合完全缓解（CRc）率达96%。3. 个体化癌症疫苗SV-102治疗转移性去势抵抗性前列腺癌（mCRPC）的1期临床试验表现亮眼，客观缓解率（ORR）达87%，完全缓解（CR）率为53%。Rinatabart sesutecan：公布1/2期临床试验数据Genmab公司日前披露旗下的候选疗法rinatabart sesutecan（Rina-S）在1/2期试验中，用以治疗复发性/晚期子宫内膜癌患者中的疗效结果。Rina-S是一种潜在“best-in-class”、叶酸受体α（FRα）靶向ADC，Genmab在去年4月收购普方生物（ProfoundBio）时获得此款疗法。截至2024年11月22日，64例接受过大量既往治疗的子宫内膜癌患者（中位3线，范围1-8）接受了100 mg/m2（n=22）或120 mg/m2（n=42）剂量的Rina-S治疗。在疗效可评估患者中，中位治疗持续时间为18.7周。分析显示，接受低（n=22）与高（n=33）剂量患者的未确认ORR分别为50%与45.5%，其中低剂量组包含2例CR。低与高剂量组患者的DCR则分别为100%和81.8%。此外，在低与高剂量组中，分别有81.8%（9/11）与80.0%（12/15）患者持续缓解。安全性方面，最常见（>25%）的治疗伴发不良事件（TEAE）在不同剂量下相似，主要是血细胞减少症和1-2级胃肠道事件（恶心、呕吐、食欲下降）。ICT01：公布1/2期联合治疗试验数据ImCheck Therapeutics公司公布了其新型γ9δ2 T细胞激活剂ICT01联用Aza-Ven治疗不适合强化化疗的新确诊AML患者的积极1/2期临床试验数据。γ9δ2 T细胞是先天免疫系统的一部分，负责对肿瘤和感染的免疫监察。ICT01是一款靶向嗜乳脂蛋白家族成员BTN3A的单克隆抗体疗法，通过与BTN3A结合，它可以选择性地激活γ9δ2 T细胞，并且促进它们迁移和浸润肿瘤，进一步激发CD8阳性T细胞和自然杀伤细胞的抗肿瘤反应。截至2025年1月20日的数据，接受推荐剂量的ICT01联合治疗的患者的CRc率为96%，CR率为74%，且各种分子亚型的患者均有缓解。值得注意的是，具有不良或中等风险突变的患者通常对Aza-Ven治疗应答较低，但接受三联疗法治疗的患者实现了高缓解率，例如TP53突变AML患者的CR和CRc率分别达到了60%和83%。此外，接受10 mg ICT01治疗的患者初步的9个月总生存率为83%。安全性方面，三联疗法在临床上具有良好的可控性。SV-102：公布1期临床试验数据Syncromune公司公布了其个体化癌症疫苗SV-102在mCRPC患者中的1期临床试验结果。数据表明，接受SV-102治疗患者的ORR为87%，53%的患者达到了CR。安全性方面，SV-102耐受性良好，观察到的TEAE多为低级别。ORIC-944：公布1b期联合治疗试验的初步数据ORIC Pharmaceuticals公司公布了其选择性PRC2别构抑制剂ORIC-944联用雄激素受体（AR）抑制剂治疗mCRPC的1b期临床试验的初步数据。截至2025年5月9日的数据，59%（10/17）的患者达到PSA50应答（即前列腺特异性抗原水平降低50%），确认的PSA50应答率为47%（1例待确认），24%（4/17）的患者达到确认的PSA90应答。在所有ORIC-944剂量水平中均观察到PSA应答，目前大多数患者仍在继续治疗，其中多名患者的治疗时间已接近一年或更长。安全性方面，ORIC-944与apalutamide或darolutamide联合使用的耐受性普遍良好，绝大多数不良事件为1/2级，与PRC2和AR抑制一致。STX-001：公布1期临床试验的初步数据Strand Therapeutics公司公布了其自我复制mRNA疗法STX-001用于治疗晚期实体瘤的1期临床试验结果。STX-001是一种脂质纳米颗粒封装的自我复制mRNA药物，可激活先天免疫系统，促进免疫原性癌细胞死亡，并表达IL-12以诱导针对肿瘤的免疫反应。在临床前模型中，STX-001表现出显著的免疫调节和抗肿瘤活性。从2024年5月29日至数据截止日期（2024年12月16日），5名完成评估的黑色素瘤患者中，有3人的非注射病灶缩小（即远隔效应），其中1例达到确认的CR，1例达到部分缓解（PR），1例靶病灶缩小100%，多个皮肤/内脏病灶出现显著的炎症反应。STX-001显示出初步良好的疗效、强烈的免疫激活作用以及可控的安全性。这些结果支持其作为单药疗法以及与免疫检查点抑制剂联合使用的进一步开发。参考资料（可上下滑动查看）[1] 오토텔릭, 'TGF-β2 ASO' 고형암 1상 "호주 IND 승인". Retrieved May 30, 2025, from https://www.biospectator.com/news/view/25209[2] Syncromune® Inc. Announces Publication of Abstract on SYNC-T® Therapy SV-102 Phase 1 Data for Metastatic Prostate Cancer at ASCO 2025 Annual Meeting. Retrieved May 30, 2025, from https://syncromune.com/2025/05/23/syncromune-inc-announces-publication-of-abstract-on-sync-t-therapy-sv-102-phase-1-data-for-metastatic-prostate-cancer-at-asco-2025-annual-meeting/[3] Autobahn Therapeutics Announces Presentation of ABX-002 Phase 1 Clinical Results at the 2025 ASCP Annual Meeting. Retrieved May 30, 2025, from https://autobahntx.com/news/autobahn-therapeutics-announces-presentation-of-abx-002-phase-1-clinical-results-at-the-2025-ascp-annual-meeting/[4] Immix Biopharma Announces Positive Results for NXC-201 at ASCO Oral Presentation, Enabling Pathway to Best-in-Class Therapy for relapsed/refractory AL Amyloidosis. Retrieved May 30, 2025, from https://immixbio.com/immix-biopharma-announces-positive-results-for-nxc-201-at-asco-oral-presentation-enabling-pathway-to-best-in-class-therapy-for-relapsed-refractory-al-amyloidosis/[5] AbelZeta Presents New Data on C-CAR168 for the Treatment of Autoimmune Diseases at LUPUS 2025. Retrieved May 30, 2025, from https://www.prnewswire.com/news-releases/abelzeta-presents-new-data-on-c-car168-for-the-treatment-of-autoimmune-diseases-at-lupus-2025-302463558.html[6] ImCheck Reports High Remission Rates in AML Patients with ICT01 Combination Therapy at ASCO 2025. Retrieved May 30, 2025, from https://www.globenewswire.com/news-release/2025/05/22/3087173/0/en/ImCheck-Reports-High-Remission-Rates-in-AML-Patients-with-ICT01-Combination-Therapy-at-ASCO-2025.html[7] Boehringer Ingelheim to present early clinical evidence of innate immune modulation and anti-tumor activity via SIRPα blockade in two ongoing trials at ASCO 2025. Retrieved May 30, 2025, from https://www.globenewswire.com/news-release/2025/05/22/3087166/0/en/Boehringer-Ingelheim-to-present-early-clinical-evidence-of-innate-immune-modulation-and-anti-tumor-activity-via-SIRP%CE%B1-blockade-in-two-ongoing-trials-at-ASCO-2025.html[8] Auron Announces First Patient Dosed in Phase 1 Clinical Trial of AUTX-703 in Advanced Hematologic Malignancies. Retrieved May 30, 2025 from https://www.globenewswire.com/news-release/2025/05/29/3090174/0/en/Auron-Announces-First-Patient-Dosed-in-Phase-1-Clinical-Trial-of-AUTX-703-in-Advanced-Hematologic-Malignancies.html[9] Genmab to Highlight New Data Evaluating Late-Stage Oncology Portfolio at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. Retrieved May 24, 2025 from https://ir.genmab.com/news-releases/news-release-details/genmab-highlight-new-data-evaluating-late-stage-oncology[10] Navigator Medicines Announces First Participants Dosed in a Phase 1b Trial of NAV-240, a Potential Best-in-Class Anti-OX40L and Anti-TNFα Bispecific Antibody Therapeutic for Autoimmune Diseases. Retrieved May 30, 2025 from https://www.businesswire.com/news/home/20250529174222/en/Navigator-Medicines-Announces-First-Participants-Dosed-in-a-Phase-1b-Trial-of-NAV-240-a-Potential-Best-in-Class-Anti-OX40L-and-Anti-TNF-Bispecific-Antibody-Therapeutic-for-Autoimmune-Diseases[11] Kura Oncology and Kyowa Kirin Announce Pivotal Monotherapy Data for Ziftomenib in Oral Presentation at the 2025 ASCO Annual Meeting. Retrieved May 23, 2025, from https://ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-and-kyowa-kirin-announce-pivotal-monotherapy-data[12] Cullinan Therapeutics, Taiho Pharmaceutical, and Taiho Oncology to Present Positive Results from Pivotal Phase 2b REZILIENT1 Trial of Zipalertinib at ASCO 2025. Retrieved May 23, 2025 from https://www.globenewswire.com/news-release/2025/05/22/3087169/0/en/Cullinan-Therapeutics-Taiho-Pharmaceutical-and-Taiho-Oncology-to-Present-Positive-Results-from-Pivotal-Phase-2b-REZILIENT1-Trial-of-Zipalertinib-at-ASCO-2025.html[13] Palisade Bio Reports Positive Phase 1a Results for PALI-2108, a First-in-Class Terminal Ileum and Colon-Targeted PDE4 B/D Inhibitor for Fibrostenotic Crohn’s Disease and Ulcerative Colitis. Retrieved May 30, 2025 from https://www.globenewswire.com/news-release/2025/05/27/3088623/0/en/Palisade-Bio-Reports-Positive-Phase-1a-Results-for-PALI-2108-a-First-in-Class-Terminal-Ileum-and-Colon-Targeted-PDE4-B-D-Inhibitor-for-Fibrostenotic-Crohn-s-Disease-and-Ulcerative-.html[14] AskBio Announces Publication of Complete Results of Phase 1b Trial of AB-1005 Gene Therapy in Participants with Parkinson’s Disease in Movement Disorders. Retrieved May 30, 2025 from https://www.globenewswire.com/news-release/2025/05/27/3088653/0/en/AskBio-Announces-Publication-of-Complete-Results-of-Phase-1b-Trial-of-AB-1005-Gene-Therapy-in-Participants-with-Parkinson-s-Disease-in-Movement-Disorders.html[15] Lupin Announces Presentation of Phase 1 Data on LNP7457 (PRMT5 inhibitor) at the American Society of Clinical Oncology - Annual Meeting 2025. Retrieved May 30, 2025 from https://www.prnewswire.com/news-releases/lupin-announces-presentation-of-phase-1-data-on-lnp7457-prmt5-inhibitor-at-the-american-society-of-clinical-oncology---annual-meeting-2025-302465586.html[16] IRLAB reports positive results from the second part of a Phase I study with IRL757. Retrieved May 30, 2025 from https://irlab.se/mfn_news/irlab-reports-positive-results-from-the-second-part-of-a-phase-i-study-with-irl757/[17] Entrada Therapeutics Receives Authorization in the European Union to Initiate ELEVATE-45-201, a Phase 1/2 Multiple Ascending Dose Clinical Study of ENTR-601-45 in Patients Living with Duchenne Muscular Dystrophy Amenable to Exon 45 Skipping. Retrieved May 30, 2025 from https://www.globenewswire.com/news-release/2025/05/28/3089307/0/en/Entrada-Therapeutics-Receives-Authorization-in-the-European-Union-to-Initiate-ELEVATE-45-201-a-Phase-1-2-Multiple-Ascending-Dose-Clinical-Study-of-ENTR-601-45-in-Patients-Living-wi.html[18] Phase I dose escalation trial of STX-001, an LNP-encapsulated self-replicating mRNA expressing IL-12, in patients (pts) with advanced solid tumors. Retrieved May 30, 2025 from https://ascopubs-org.libproxy1.nus.edu.sg/doi/10.1200/JCO.2025.43.16_suppl.9556[19] ORIC® Pharmaceuticals Announces Potentially Best-In-Class Preliminary Efficacy and Safety Data from Ongoing Phase 1b Trial of ORIC-944 in Combination with AR Inhibitors for the Treatment of Patients with mCRPC. Retrieved May 30, 2025 from https://www.globenewswire.com/news-release/2025/05/28/3089929/0/en/ORIC-Pharmaceuticals-Announces-Potentially-Best-In-Class-Preliminary-Efficacy-and-Safety-Data-from-Ongoing-Phase-1b-Trial-of-ORIC-944-in-Combination-with-AR-Inhibitors-for-the-Trea.html[20] AKTIS ONCOLOGY INITIATES PHASE 1B CLINICAL TRIAL OF ITS NECTIN-4-TARGETING RADIOPHARMACEUTICAL PRODUCT CANDIDATE, AKY-1189, ACROSS MULTIPLE TUMOR TYPES. Retrieved May 30, 2025 from https://www.prnewswire.com/news-releases/aktis-oncology-initiates-phase-1b-clinical-trial-of-its-nectin-4-targeting-radiopharmaceutical-product-candidate-aky-1189-across-multiple-tumor-types-302466453.html[21] Enveda Reports Favorable Phase 1 Safety for Novel Oral Anti-Inflammatory, Launches Phase 1b Trial in Atopic Dermatitis. Retrieved May 30, 2025 from https://www.businesswire.com/news/home/20250528125414/en/Enveda-Reports-Favorable-Phase-1-Safety-for-Novel-Oral-Anti-Inflammatory-Launches-Phase-1b-Trial-in-Atopic-Dermatitis[22] Phanes Therapeutics announces first patient dosed in clinical study of mavrostobart (PT199) in combination with chemotherapy. Retrieved May 30, 2025 from https://www.prnewswire.com/news-releases/phanes-therapeutics-announces-first-patient-dosed-in-clinical-study-of-mavrostobart-pt199-in-combination-with-chemotherapy-302464552.html[23] TIXiMED Announces Successful Completion of a Phase 1 Study of its Novel Oral Disease-Modifying Type 1 Diabetes Therapy. Retrieved May 30, 2025 from https://www.businesswire.com/news/home/20250529307401/en/TIXiMED-Announces-Successful-Completion-of-a-Phase-1-Study-of-its-Novel-Oral-Disease-Modifying-Type-1-Diabetes-Therapy免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新2

ImCheck Reports High Remission Rates in AML Patients with ICT01 Combination Therapy at ASCO 2025 ICT01 in combination with azacitidine and venetoclax (Aza-Ven) achieves unprecedented high remission rates overall and across molecular subtypes in newly diagnosed AML patients Favorable safety profile , with Grade ≥3 adverse events consistent with expected Aza-Ven hematological toxicity and AML-related effects ICT01 10 mg is the proposed dose for further clinical development Oral presentation at ASCO 2025: Monday, June 2, 2025, 5:12 p.m.- 5:24 p.m. CDT, Room S100a Marseille, France, May 22, 2025, 5:00 pm ET/11:00 pm CET – ImCheck Therapeutics today announced the publication of its abstract for an upcoming oral presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. The presentation will feature updated data from the ongoing Phase I/II EVICTION study. The study evaluates ICT01, a novel γ9δ2 T-cell activator, administered in combination with azacitidine and venetoclax (Aza-Ven) in patients with newly diagnosed acute myeloid leukemia (AML) who are unfit for intensive chemotherapy. The updated interim results demonstrate a 96% composite complete remission (CRc) rate, including 74% complete remissions (CR), with responses observed across molecular subtypes. Notably, high response rates were achieved in patients with adverse- or intermediate-risk mutations, a population typically less responsive to Aza-Ven. In addition, the preliminary 9-month overall survival rate for patients treated with 10 mg of ICT01 was 83%, underscoring the strong clinical potential of the novel triple combination. The oral presentation will be held 5:12 p.m.- 5:24 p.m. CDT, on Monday, June 2, during Session “Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant” (Room S100a). “The updated data reinforce ICT01’s potential to meaningfully enhance the therapeutic effects of Aza-Ven in AML by harnessing the unique biology of γ9δ2 T cells, ” said Stephan Braun , MD, PhD, Chief Medical Officer of ImCheck Therapeutics. “The depth and consistency of responses observed with ICT01, combined with its manageable safety profile, provide a strong foundation as we advance toward a randomized study.” Key Highlights : Patient population : At the data cut-off on January 20, 2025, 45 patients aged 51 to 87 were enrolled. A total of 29 patients received 10 mg of ICT01 and 16 patients received 75 mg of ICT01, each in combination with Aza-Ven; of these, 39 patients were evaluable for efficacy. Clear signs of immune activation : ICT01 at the 10 mg dose provided optimal activation of γ9δ2 T cells and a downstream immune cascade, supporting its role in enhancing Aza-Ven efficacy, and confirming it as the proposed dose for further clinical development. Strong efficacy for ICT01 with Aza-Ven : Treatment with ICT01 at the proposed dose in combination with Aza-Ven resulted in high rates of CRc (96%) and CR (74%). Encouraging efficacy in difficult-to-treat AML patients: Among evaluable patients, the majority had adverse- or intermediate-risk genetic aberrations, which are typically associated with limited clinical benefit from Aza-Ven. Specifically, the CR and CRc rates in patients with TP53 -mutated AML were 60% and 83%, respectively. Early survival trends: At a median follow-up time of 8.5 months, high response rates were associated with a longer duration of response and an improved 9-month overall survival. While these time-to-event data are encouraging, they remain preliminary because the majority of patients are still on treatment. Favorable safety profile : The combination treatment was clinically well manageable, with a low 30-day mortality rate of 4% (all deaths unrelated to ICT01) and a low rate of infectious complications. The most frequent adverse events of Grade ≥3 were febrile neutropenia, neutropenia, thrombocytopenia, and sepsis, reported as unrelated to ICT01 and consistent with the known hematological toxicity of Aza-Ven. “Patients with newly diagnosed AML, particularly those with high-risk genetic features, continue to face limited therapeutic options . Our results suggest that ICT01’s ability to engage γ9δ2 T cells could offer a powerful new option for a population typically underserved by current therapies, ” added Pierre d’Epenoux , Chief Executive Officer of ImCheck Therapeutics. “Based on this compelling validation of our novel approach and the momentum we are building as an organization, we will accelerate clinical development of ICT01 in patients with AML, myelodysplastic syndrome, and select solid tumor indications. We are grateful for the patients’ participation in our study and the support from the investigators, the ImCheck team and our investors .” *** About the medical need in AML Acute myeloid leukemia (AML) remains a significant clinical challenge, particularly for older or unfit patients who cannot tolerate intensive chemotherapy. While the combination of venetoclax and azacitidine has become the standard non-intensive regimen, it is not curative and relapse rates remain high. Most patients are not eligible for stem cell transplantation, often due to age, comorbidities, or insufficient response, and face limited treatment options and poor overall survival. Despite AML’s known sensitivity to immune-mediated control, current immunotherapies targeting PD-1, TIM-3, or CD47 have not delivered meaningful clinical benefit. This underscores the urgent need for novel immuno-oncology approaches. Recently, γ9δ2 T cells, with their cytotoxic activity and unique dual role in both innate and adaptive immunity, have emerged as promising immune modulators. Their association with reduced relapse and prolonged survival, particularly in the post-transplant setting, suggests that enhancing their anti-leukemic potential could offer a meaningful new treatment option for high-risk AML patients. About the EVICTION Study EVICTION is a first-in-human, dose-escalation (Part 1) and cohort-expansion (Part 2) clinical study of ICT01 in patients with various advanced relapsed or refractory solid or hematologic cancers that have exhausted standard-of-care treatment options. Part 1 (Phase I) is designed to characterize the preliminary safety, tolerability, and pharmacodynamic activity of increasing doses of ICT01 as monotherapy (Group A: solid tumors; Group B: hematologic tumors) and in combination with pembrolizumab (Group C: solid tumors). Part 2 comprises randomized dose-optimizing and efficacy estimating expansion cohorts of monotherapy (Group D: ovarian cancer; Group E: prostate cancer) and combination treatment of patients with AML (Group F), melanoma (Group G), urothelial cell carcinoma (Group H), or head-and-neck squamous cell carcinoma (Group I). More information on the EVICTION study can be found at clinicaltrials.gov (NCT04243499). About ICT01 ICT01 is a humanized, anti-BTN3A (also known as CD277) monoclonal antibody that selectively activates γ9δ2 T cells, which are responsible for immunosurveillance of malignancy and infections. The three isoforms of BTN3A targeted by ICT01 are overexpressed on many solid tumors (e.g., melanoma, urothelial cell, colorectal, ovarian, pancreatic, and lung cancer) and hematologic malignancies (e.g., leukemia and lymphomas) and also expressed on the surface of innate (e.g., γδ T cells and NK cells) and adaptive immune cells (T cells and B cells). BTN3A is essential for the activation of the anti-tumor immune response of γ9δ2 T cells. As demonstrated by data presented at past AACR, ASCO, ASH, ESMO and SITC conferences, ICT01 selectively activates circulating γ9δ2 T cells leading to migration of γ9δ2 T cells out of the circulation and into the tumor tissue and triggers a downstream immunological cascade through secretion of pro-inflammatory cytokines, including but not limited to IFNγ and TNFα, further augmenting the anti-tumor immune response. Anti-tumor activity and efficacy of ICT01 have been shown in patients across several cancer indications. About IMCHECK THERAPEUTICS ImCheck Therapeutics is developing a new generation of immunotherapeutic antibodies targeting butyrophilins, a novel superfamily of immunomodulators. By unlocking the power of γ9δ2 T cells, ImCheck’s innovative approach has the potential to transform treatments across oncology, autoimmune, and infectious diseases. The lead clinical-stage program, ICT01, has been advancing to late-stage trials, demonstrating a unique mechanism of action that modulates both innate and adaptive immunity. These “first-in-class” activating antibodies may deliver superior clinical outcomes compared to first-generation immunotherapy approaches, in particular in rationale combinations with immune checkpoint inhibitors and immunomodulatory anti-cancer drugs. Additionally, ImCheck’s pipeline compounds are progressing toward clinical development for autoimmune and infectious diseases. The company benefits from the pioneering research of Prof. Daniel Olive (INSERM, CNRS, Institut Paoli Calmettes, Aix-Marseille University), a global leader in γ9δ2 T cells and butyrophilins, as well as the expertise of a seasoned management team and the commitment of leading U.S. and European investors. For further information: https://www.imchecktherapeutics.com/ Press contacts: US and EU Trophic Communications Gretchen Schweitzer +49 (0) 172 861 8540 imcheck@trophic.eu France ATCG PARTNERS Céline Voisin +33 (0)6 62 12 53 39 imcheck@atcg-partners.com Attachment Download Press Release 25/05/22 Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.