Abstract CT021: Preliminary clinical results of a therapeutic cancer vaccine PDC*lung01 in combination with anti-PD-1 in patients (pts) with stage IV NSCLC

作者: Althoff, Friederike ; Biesma, Bonne ; Cuppens, Kristof ; Pons-Tostivint, Elvire ; Wauters, Els ; Renard, Florence ; Adriaenssens, Stefanie ; Vansteenkiste, Johan ; Theelen, Willemijn ; Plumas, Joel ; Borm, Frank ; Skrzypski, Marcin ; Derijcke, Sofie ; Perol, Maurice ; Moro-Sibilot, Denis ; Debruyne, Channa ; Cantero, Frederique ; Sibille, Anne ; Demedts, Ingel ; Colinet, Benoit ; Van de Kerkhove, Charlotte ; De Vos, Beatrice ; Buchmeier, Eva-Lotte

AbstractBackground PDC*lung01 (IMP) is a therapeutic cancer vaccine based on an irradiated plasmacytoid dendritic cell line loaded with HLA-A*02:01-restricted peptides (NY-ESO-1, MAGE-A3, MAGE-A4, Multi-MAGE-A, MUC1, Survivin and Melan-A), able to prime and expand peptide-specific CD8+ T cells in vitro and in vivo, and is synergistic with anti-PD-1.Methods In this phase I/II study, HLA-A*02 positive NSCLC pts were enrolled in 4 cohorts: resected stage II/IIIA in adjuvant setting treated with low dose (A1) or high dose (A2) of IMP following SOC; or untreated stage IV NSCLC with measurable disease, PD-L1≥50% and no targetable driver mutation, treated with low dose (B1) or high dose (B2) of IMP in combination to pembrolizumab 200mg q3w, continuously. IMP was simultaneously administered by SC and IV route weekly for 6 consecutive doses. Objective response rate (ORR) and progression-free survival (PFS) were assessed in cohort B2. We report herein preliminary efficacy results of the first 21 pts analysed when the 19th evaluable patient reached the 9-months PFS and the safety of 38 pts.Results Out of 21, 19 pts receiving at least 5 doses of IMP and having 1 post-baseline radiological evaluation were evaluated. The median follow-up was 12.5 months. The best objective response (BOR) included 12 PR (63.2%) and 7 SD (36.8%) with ORR of 63.2% (80% CI 45.9% - 78.2%) and a disease control rate (DCR) of 94.7%. The 9mPFS according to the Kaplan-Meier estimate was 52.1% (80% CI 36.5% - 65.56%). The mPFS was 10.9 months. The median duration of response was 9.49 months. An antigen-specific CD8+ T-cell response was induced against the lung antigens of the IMP in 68.4% of pts. Immune responses with remarkable expanded anti-tumor CD8+ T-cells were observed both in PR and SD. More immune response results will be available in the final analysis of the 45 pts of cohort B2. Treatment-related AEs (TRAEs) were mostly Grade 1-2. Only 1 severe TRAE occurred, a Grade 4 allergic infusion-related reaction, leading to IMP discontinuation. Thirteen pts experienced a serious AE, of which 3 were considered causally related to the IMP.Conclusions The BOR, ORR, DCR, PFS, duration of response and safety of PDC*lung01 in combination with anti-PD-1 showed encouraging signals suggesting that this combination may provide a clinical meaningful tumour response in stage IV NSCLC population with a mild safety profile. Interestingly, the immune response observed confirms the mechanism of action of the IMP in relation to clinical activity.Citation Format: Willemijn Theelen, Maurice Perol, Kristof Cuppens, Ingel Demedts, Frank Borm, Bonne Biesma, Els Wauters, Benoit Colinet, Eva-Lotte Buchmeier, Friederike Althoff, Elvire Pons-Tostivint, Charlotte Van de Kerkhove, Denis Moro-Sibilot, Anne Sibille, Sofie Derijcke, Marcin Skrzypski, Joel Plumas, Beatrice De Vos, Channa Debruyne, Frederique Cantero, Stefanie Adriaenssens, Florence Renard, Johan Vansteenkiste. Preliminary clinical results of a therapeutic cancer vaccine PDC*lung01 in combination with anti-PD-1 in patients (pts) with stage IV NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT021.

2024-03-22·Cancer Research

Abstract 1182: PDC*lung01: An innovative therapeutic cancer vaccine induces specific immune responses in combination with anti- PD-1 treatment in patients with non-small cell lung cancer

作者: Colinet, Benoit ; Sibille, Anne ; Cuppens, Kristof ; Perol, Maurice ; Moro-Sibilot, Denis ; Demedts, Ingel ; Theelen, Willemijn ; Plumas, Joel ; Duchayne, Camille ; Badawy, Kays Al ; Skrzypski, Marcin ; Wauters, Els ; Buchmeier, Eva-Lotte ; Biesma, Bonne ; Borm, Frank ; Derijcke, Sofie ; Van de Kerkhove, Charlotte ; Vansteenkiste, Johan ; Debruyne, Channa ; Pons-Tostivint, Elvire ; Devos, Beatrice ; Collodoro, Mike

AbstractWe have developed an innovative cancer vaccine for the treatment of advanced NSCLC patients in combination with checkpoint inhibitors. This PDC*lung01 product based on an irradiated plasmacytoid dendritic cell line loaded with HLA-A*02:01 restricted peptides (NY-ESO-1, MAGE-A3, MAGE-A4, Multi-MAGE-A, MUC1, Survivin and Melan-A) is able to prime and expand peptide-specific CD8+ T cells in vitro and in vivo, and is synergistic with anti-Programmed Death (PD)-1 (Plumas et al, 2022; Hannani et al, 2023, NCT03970746). In study PDC-LUNG-101 with EudraCT number 2018-002382-19, PDC*lung01 is injected intravenously and subcutaneously for 6 times at two dose levels, 14 million, or 140 million cells in stage II/IIIA (cohort A1 & A2, monotherapy) or stage IV with TPS≥50% (cohort B1 & B2; in combination with pembrolizumab) patients. We report here the analysis of immune response of 3 cohorts (A1, A2, B1) of patients and the first 19 patients out of 42 (cohort B2) treated with high dose of PDC*lung01 in combination with Pembrolizumab at baseline and 3 timepoints post injection. Several circulating immune parameters have been evaluated at different times before and after vaccination using different assays we have developed: leukocyte count and determination of circulation peptide specific CD8+ T cells by flow cytometry using multimer tools without prior in vitro culture. The assay made on purified CD8+ T-cells allowed us to define a limit of quantification (LOQ) to accurately assess the fold changes of the cell expansion. In addition, tumor microenvironment (TME) was analyzed by multiplex fluorescence immunochemistry. The data of 42 patients for who an immune response has been evaluated (cohorts A and B) will be presented. No major changes in circulating main lymphocyte frequencies (B cells, NK cells, CD4+, CD8+, or Treg T cells) were observed during treatment. In addition, no major cell activation (CD25+, CD54, or DR+) was noted. In contrast, in a significant number of patients, PDC*lung01 induced circulating peptide-specific CD8+ T cell expansion in all 4 cohorts at different levels and time points against at least one out of seven peptides used. The percentages of patients for who an expansion of antigen-specific T-cell were observed were 50%, 64%, 66.7% and 68.4% in A1, A2, B1 and B2 cohorts respectively. The intensity of the immune response was proportional to the dose of PDC*lung01 and to the combination with pembrolizumab. When possible, total and peptide-specific CD8+ T cells were sorted for analysis of TCR repertoire, illustrating the modelling and dynamics of the immune response. The TME features will also be illustrated. To conclude, treatment with PDC*lung01 induces an anti-tumor immune response in a significant number of patients which appears to be enhanced by the combination with pembrolizumab.Citation Format: Joel Plumas, Anne Sibille, Ingel Demedts, Elvire Pons-Tostivint, Charlotte Van de Kerkhove, Sofie Derijcke, Willemijn Theelen, Bonne Biesma, Frank Borm, Els Wauters, Mike Collodoro, Kays Al Badawy, Camille Duchayne, Channa Debruyne, Beatrice Devos, Benoit Colinet, Denis Moro-Sibilot, Maurice Perol, Eva-Lotte Buchmeier, Marcin Skrzypski, Kristof Cuppens, Johan Vansteenkiste. PDC*lung01: An innovative therapeutic cancer vaccine induces specific immune responses in combination with anti- PD-1 treatment in patients with non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1182.

2023-01-30·Genes & Cancer

Leveraging a powerful allogeneic dendritic cell line towards neoantigen-based cancer vaccines

Article

作者: Leplus, Estelle ; Plumas, Joël ; Chaperot, Laurence ; Laulagnier, Karine ; Hannani, Dalil

In recent years, immunotherapy has finally found its place in the anti-cancer therapeutic arsenal, even becoming standard of care as first line treatment for metastatic forms. The clinical benefit provided by checkpoint blockers such as anti-PD-1/PD-L1 in many cancers revolutionized the field. However, too many patients remain refractory to these treatments due to weak baseline anti-cancer immunity. There is therefore a need to boost the frequency and function of patients' cytotoxic CD8+ cellular effectors by targeting immunogenic and tumor-restricted antigens, such as neoantigens using an efficient vaccination platform. Dendritic cells (DC) are the most powerful immune cell subset for triggering cellular immune response. However, autologous DC-based vaccines display several limitations, such as the lack of reproducibility and the limited number of cells that can be manufactured. Here we discuss the advantages of a new therapeutic vaccine based on an allogeneic Plasmacytoid DC cell line, which is easy to produce and represents a powerful platform for priming and expanding anti-neoantigen cytotoxic CD8+ T-cells.

项与 PDC Line Pharma SASU 相关的新闻（医药）

2024-04-14

·药明康德

完全缓解率达83%的联合疗法；疾病控制率近95%的肺癌免疫联合疗法 | 一周盘点

▎药明康德内容团队编辑本期看点1. 个体化治疗性癌症疫苗GNOS-PV02联用PD-1抑制剂与PD-1抑制剂单药相比，在一项早期临床试验中使晚期肝癌患者的总缓解率（ORR）近翻倍，患者的中位总生存期（mOS）获大幅延长。2. 癌症疫苗PDC*lung01联用PD-1抑制剂一线治疗转移性非小细胞肺癌（NSCLC），在一项1/2期临床试验中的疾病控制率（DCR）高达94.7%。3. CD47抑制剂evorpacept联用利妥昔单抗和来那度胺治疗惰性和侵袭性复发/难治性B细胞非霍奇金淋巴瘤（B-NHL），在一项1/2期临床试验中的ORR为94%，完全缓解（CR）率为83%。4. 长效IL-2超级激动剂MDNA11治疗晚期实体肿瘤，使1例转移性胰腺导管腺癌（PDAC）患者在基线时存在的所有病变完全消退。药明康德内容团队整理GNOS-PV02：公布1/2期临床试验数据Geneos Therapeutics公司公布其个体化治疗性癌症疫苗GNOS-PV02的1/2期临床试验全部入组患者的安全性、免疫原性和疗效数据。这项试验中使用的癌症疫苗是一款DNA质粒递送的新抗原疫苗。该公司通过对每例患者的肿瘤进行测序，发现基于每个患者独特的肿瘤突变产生的新抗原，然后将表达这些新抗原的DNA序列导入到DNA质粒中。这种基于DNA的个体化治疗性癌症疫苗可能包含多达40种新抗原。此次公布的结果显示，该试验达到了安全性和免疫原性的主要终点，以及基于缓解率的疗效次要终点。在36名晚期肝癌患者中，有11名（30.6%）对该疫苗与PD-1抑制剂Keytruda联合疗法产生缓解，这大约是过去对照药物缓解率的两倍。其中3例患者达到了CR，8例患者达到了部分缓解（PR）。数据截止时，患者的mOS为19.9个月，而先前报道的Keytruda和其他PD-1抑制剂单药用于二线治疗时的mOS范围为12.9-15.1个月。▲GNOS-PV02治疗晚期肝癌患者的临床结果（图片来源：参考资料[28]）此外，免疫学分析证实，在14名可评估的患者中，100%的患者出现了对疫苗编码的新抗原的新T细胞反应。单细胞测序分析显示，这些T细胞克隆中的绝大多数是CD8 T效应记忆细胞，这是诱导抗肿瘤细胞毒性的关键细胞。PDC*lung01：公布1/2期临床试验的新数据 PDC*line Pharma公司公布了其用于NSCLC患者的现货型治疗性癌症疫苗候选药物PDC*lung01单药或与抗PD-1治疗联用的1/2期临床试验中最后一批患者的中期数据。浆细胞样树突状细胞（PDC）系是一种有效的专业抗原呈递细胞系，能够激发和增强患者的抗肿瘤细胞毒性CD8+ T细胞，并能与抗PD-1治疗协同作用。PDC*lung01是由7种活性组分组成的细胞悬液，装载着多种肿瘤抗原。此次公布的数据显示，中位随访时间为12.5个月时，在19例可评估的患者中，高剂量PDC*lung01与pembrolizumab联用一线治疗IV期（转移性）NSCLC患者的DCR为94.7%，ORR为63.2%，获得缓解的患者均为PR。患者的中位无进展生存期（mPFS）为10.9个月，中位缓解持续时间为9.49个月。Evorpacept（ALX148）：公布1/2期临床试验数据ALX Oncology公布了其CD47抑制剂evorpacept（ALX148）联用利妥昔单抗和来那度胺治疗惰性和侵袭性复发/难治性B细胞非霍奇金淋巴瘤的1/2期临床试验数据。Evorpacept是一种下一代CD47阻断疗法，它将高亲和性CD47结合结构域与经特殊处理的Fc结构域相结合，因此无法激活Fc受体，有望降低CD47靶向抗体因激活Fc受体可能产生的毒副作用。此外，与其它抗CD47抗体相比，evorpacept的分子量更小，更容易渗透到实体瘤中，从而提高疗效。截至目前，evorpacept已在500多名受试者中使用，并在与各种抗癌抗体联用时，在一系列血液和实体恶性肿瘤中显示出良好的活性和耐受性。该研究中，20名惰性和2名侵袭性复发/难治性B-NHL患者接受了evorpacept联用利妥昔单抗和来那度胺的治疗，该组合疗法的耐受性良好，安全性与利妥昔单抗联用来那度胺相似，未报告剂量限制性毒性。接受evorpacept联用利妥昔单抗和来那度胺的患者的最佳ORR为94%，83%的患者实现了CR。与之相比，在先前的一项3期基准试验中，接受利妥昔单抗联用来那度胺的此类患者的ORR为78%，CR率为34%。MDNA11：公布1/2期临床试验的新数据 Medicenna Therapeutics公司公布了其下一代长效IL-2超级激动剂MDNA11治疗晚期实体瘤的新临床结果。MDNA11具有优秀的CD122（IL-2受体β）结合作用，而没有CD25（IL-2受体α）亲和力，从而能优先刺激癌症杀伤效应T细胞和NK细胞。此次公布的结果显示，MDNA11的耐受性良好，没有报告剂量限制毒性和血管渗漏综合征。截至2024年3月22日的数据，14例患者中有4例达到了PR，3例达到了疾病稳定（SD），ORR为29%，DCR为50%。MDNA11已使3名转移性黑色素瘤患者获得了6个月至18个月的持久SD，并且这些患者的肿瘤有缩小。第66周时，1例转移性胰腺导管腺癌患者在基线时存在的所有病变均完全消退。一例双检查点抑制剂治疗后进展的黑色素瘤患者的靶病灶在第28周时完全消退，非靶病灶在第36周持续缩小。Autogene cevumeran（BNT122，RO7198457）：公布1期临床试验的新数据 BioNTech公司在2024年美国癌症研究协会（AACR）年会上，公布了其针对胰腺导管腺癌的个体化癌症疫苗autogene cevumeran的临床试验随访成果。Autogene cevumeran是基于BioNTech的iNeST癌症疫苗技术平台生成的个体化新抗原疫苗，它可以编码数十种新抗原，旨在激发人体针对肿瘤细胞产生更为全面的免疫反应，防止肿瘤细胞逃避免疫系统的攻击。此前公布的结果显示，16名接受过手术治疗的患者在atezolizumab治疗后接受了autogene cevumeran治疗。在这16人中，8人（50%）产生了T细胞免疫反应，由疫苗诱导产生了大量新抗原特异性的T细胞——其中一半的T细胞可以靶向一种以上的新抗原。▲去年5月所公布autogene cevumeran与抗PD-L1抗体atezolizumab和化疗联用，治疗PDAC患者的疗效结果（图片来源：参考资料[27]）此次公布的分析表明，患者在接种PDAC癌症疫苗3年后，体内的T细胞免疫应答持续激活，并且患者的无复发生存期（RFS）得到了持续的延长。这一结果印证了该癌症疫苗的免疫持久性。DOC1021：公布1期临床试验的中期数据Diakonos Oncology公司公布了其树突状细胞疫苗DOC1021用于治疗多形性胶质母细胞瘤（GBM）患者的1期开放标签试验的中期分析结果。该公司的树突状细胞疫苗由患者自身的免疫细胞与从肿瘤样本中提取的RNA和蛋白质结合制成。这种独特的方法可以靶向完整的癌症抗原谱，而无需进行任何基因修饰。通过利用天然的免疫信号通路，这种策略使免疫系统能将癌细胞视同病毒感染的细胞一样进行识别和清除。此次公布结果时，GBM患者的mOS期尚未达到，但有望大幅超过接受标准治疗（SOC）患者12.7个月的预期mOS。平均随访时间为12.9个月时，16名新确诊的GBM患者中有12名仍然存活，且未发生可归因的严重不良事件。2021年10月入组的首例GBM患者已存活了两年多。尽管接受的治疗剂量不到预计治疗剂量的25%，接下来入组的4名患者中的每一位都存活了15个月以上，其中两名在20.3个月和17.5个月时仍然存活。MGMT未甲基化GBM患者目前的12个月生存率为88%，而接受SOC的MGMT未甲基化GBM患者的12个月生存率仅为53%。OBX-115：公布1期临床试验的新数据 Obsidian Therapeutics公司公布了其肿瘤浸润淋巴细胞（TIL）疗法OBX-115用于晚期或转移性黑色素瘤患者的1期临床试验的最新进展，包括25周的中期研究随访安全性数据和最新的详细疗效数据。OBX-115是一种新型工程化的TIL疗法，该TIL具有表达于细胞膜上受调节的白介素-15（IL-15）蛋白，因此患者在接受OBX-115治疗时不需要同时接受传统TIL治疗方案中要求的高剂量IL-2。临床前数据显示，与未经改造的TIL疗法相比，OBX-115具有增强的持久性与效力，动物模型的肿瘤控制得到改善，因此具潜力改善不同类型实体瘤患者的临床结果。此次公布的结果显示，OBX-115的耐受性良好，与使用高剂量IL-2的非工程化TIL疗法具有差异化的安全性，未报告剂量限制性毒性和≥4级的非血液学事件。OBX-115诱导了深入且持久的缓解，ORR为50%，其中CR率为33%，mPFS尚未达到，6个月无进展生存率为67%。此外，所有患者在接受治疗后肿瘤负荷有所减轻，疾病控制时间≥12周。TILT-123：公布1期临床试验的初步数据 TILT Biotherapeutics公司公布了其溶瘤病毒疗法TILT-123联合Keytruda治疗铂类耐药或难治性卵巢癌的1期临床试验的安全性和有效性数据。TILT-123是一种溶瘤腺病毒，不但能够在肿瘤内部复制、裂解肿瘤并且释放肿瘤相关抗原，还可以产生免疫刺激细胞因子TNFα和IL-2。该病毒的另一个优势是它不会在正常细胞中繁殖，而且可以使用肿瘤内注射或者静脉注射给药。TILT-123在临床前癌症模型中表现出100%的缓解率。这项研究中，患者接受了瘤内或腹膜内注射TILT-123联合静脉注射Keytruda的治疗。结果显示，71%可评估患者的疾病得到了控制，其中一名粘液腺癌患者获得了长期PR。注射和未注射的肿瘤都出现了肿瘤体积缩小和显著的免疫调节，这表明该疗法有可能导致全身性的缓解。ELVN-001：公布1期临床试验数据 Enliven Therapeutics公司公布了其小分子激酶抑制剂ELVN-001治疗复发/难治性或对现有酪氨酸激酶抑制剂（TKI）不耐受的慢性髓系白血病（CML）患者的1期临床试验的积极数据。ELVN-001是一种强效、高选择性、潜在“best-in-class”的小分子激酶抑制剂，专门针对CML患者的致癌驱动因子BCR-ABL融合蛋白。ELVN-001还具有针对耐药性最强的BCR-ABL1耐药突变体T315I和其他已知耐药突变体的活性。截至2024年3月18日的数据，ELVN-001的耐受性良好，未报告≥3级治疗相关的非血液学毒性反应。治疗12周时，既往接受过asciminib和/或对TKI耐药的患者的初始累积主要分子缓解（MMR）率为44%（7/16），与已获批的BCR-ABL1酪氨酸激酶抑制剂在1期临床试验中的数据相比具有优势。在可评估的患者中，所有患者在12周时BCR-ABL1融合蛋白的转录水平都有改善或保持稳定。大家都在看药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看）[1] Inozyme Pharma Announces Positive Topline Data from Ongoing Phase 1/2 Trials of INZ-701 in Adults with ABCC6 Deficiency (PXE) and ENPP1 Deficiency. 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Retrieved April 9, 2024, from https://www.globenewswire.com/news-release/2024/04/09/2860391/0/en/Medicenna-Presents-Updated-Results-of-Single-Agent-MDNA11-Anti-tumor-Activity-from-Dose-Escalation-and-Ongoing-Dose-Expansion-of-the-Phase-1-2-ABILITY-1-Study-at-the-2024-Annual-Me.html[15] Corvus Pharmaceuticals Announces Initiation of Placebo-Controlled Phase 1 Clinical Trial of Soquelitinib for Atopic Dermatitis. Retrieved April 9, 2024, from https://www.globenewswire.com/news-release/2024/04/09/2860339/0/en/Corvus-Pharmaceuticals-Announces-Initiation-of-Placebo-Controlled-Phase-1-Clinical-Trial-of-Soquelitinib-for-Atopic-Dermatitis.html[16] Diakonos Oncology’s Unique Dendritic Cell Vaccine (DOC1021) Improves Survival Compared to Standard of Care in Phase 1 Trial for Glioblastoma. Retrieved April 9, 2024, from https://www.diakonosoncology.com/blog/diakonos-oncologys-unique-dendritic-cell-vaccine-doc1021-improves-survival-compared-to-standard-of-care-in-phase-1-trial-for-glioblastoma/[17] Vanqua Bio Announces First Patient Dosed in Phase 1 Clinical Trial Evaluating VQ-101, its Small Molecule GCase Activator for GBA-Parkinson’s Disease and Related Disorders. Retrieved April 9, 2024, from https://www.globenewswire.com/news-release/2024/04/09/2859875/0/en/Vanqua-Bio-Announces-First-Patient-Dosed-in-Phase-1-Clinical-Trial-Evaluating-VQ-101-its-Small-Molecule-GCase-Activator-for-GBA-Parkinson-s-Disease-and-Related-Disorders.html[18] Obsidian Therapeutics Presents Positive 25-Week Median Study Follow-Up Safety and Efficacy Data from First-in-Human Study of OBX-115 in Advanced Melanoma at the American Association for Cancer Research Annual Meeting. Retrieved April 9, 2024, from https://www.businesswire.com/news/home/20240409687216/en/[20] Tr1X Announces FDA Clearance of First Investigational New Drug Application for TRX103, an Allogeneic Regulatory T-Cell Therapy to Treat Autoimmune Diseases. Retrieved April 11, 2024, from https://www.prnewswire.com/news-releases/tr1x-announces-fda-clearance-of-first-investigational-new-drug-application-for-trx103-an-allogeneic-regulatory-t-cell-therapy-to-treat-autoimmune-diseases-302112587.html[21] ViGeneron Announces First Patient Dosed in Phase 1b Clinical Trial of VG901 For the Intravitreal Treatment of Retinitis Pigmentosa. Retrieved April 11, 2024, from https://vigeneron.com/press/vigeneron-announces-first-patient-dosed-in-phase-1b-clinical-trial-of-vg901-for-the-intravitreal-treatment-of-retinitis-pigmentosa/[22] TILT Biotherapeutics Presents Clinical Data on TILT-123 in Combination with KEYTRUDA® (pembrolizumab) for Ovarian Cancer at AACR 2024. Retrieved April 11, 2024, from https://www.globenewswire.com/news-release/2024/04/10/2860497/0/en/TILT-Biotherapeutics-Presents-Clinical-Data-on-TILT-123-in-Combination-with-KEYTRUDA-pembrolizumab-for-Ovarian-Cancer-at-AACR-2024.html[23] Enliven Therapeutics Announces Positive Proof of Concept Data from Phase 1 Clinical Trial of ELVN-001 in Chronic Myeloid Leukemia. Retrieved April 11, 2024, from https://ir.enliventherapeutics.com/news-releases/news-release-details/enliven-therapeutics-announces-positive-proof-concept-data-phase[24] Possible New Hope for Metastatic Cancer Patients: Food and Drug Administration Grants Approval for Clinical Trials For Lamassu's Groundbreaking Cancer Treatment Protocol. Retrieved April 11, 2024, from https://www.prnewswire.com/news-releases/possible-new-hope-for-metastatic-cancer-patients-food-and-drug-administration-grants-approval-for-clinical-trials-for-lamassus-groundbreaking-cancer-treatment-protocol-302114390.html[25] MEI Pharma Reports Initial Data from Clinical Study Evaluating ME-344 in Combination with Bevacizumab (Avastin®) in Relapsed Metastatic Colorectal Cancer Patients. Retrieved April 11, 2024, from https://www.businesswire.com/news/home/20240411126658/en[26] Boundless Bio Announces First Patient Dosed in First-in-Human Phase 1/2 Clinical Trial of BBI-825 in Cancer Patients with Resistance Gene Amplifications. Retrieved April 11, 2024, from https://www.businesswire.com/news/home/20240410633469/en[27] Rojas et al., (2023). Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature, https://doi.org/10.1038/s41586-023-06063-y[28] Yarchoan M, Gane EJ, Marron TU, Perales-Linares R, Yan J, Cooch N, Shu DH, Fertig EJ, Kagohara LT, Bartha G, Northcott J, Lyle J, Rochestie S, Peters J, Connor JT, Jaffee EM, Csiki I, Weiner DB, Perales-Puchalt A, Sardesai NY. Personalized neoantigen vaccine and pembrolizumab in advanced hepatocellular carcinoma: a phase 1/2 trial. Nat Med. 2024 Apr 7. doi: 10.1038/s41591-024-02894-y. Epub ahead of print. PMID: 38584166.[29] Silence Therapeutics Announces JAMA Publication of Additional Phase 1 Data for Zerlasiran in Subjects with Elevated Lipoprotein(a). Retrieved April 11, 2024, from https://www.businesswire.com/news/home/20240408451903/en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：本文来自药明康德内容团队，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

疫苗免疫疗法临床结果

2024-01-17

·Business Wire

PDC*line Pharma and Partners Receive €8.1M From Walloon Region and Wallonia Health Cluster BioWin for Personalized Therapeutic Vaccine Project

LIÈGE, Belgium & GRENOBLE, France--( BUSINESS WIRE )--PDC*line Pharma, a clinical stage biotech company developing a new class of potent and scalable active immunotherapies for cancer, announces today the selection of the PDC*neo+ project for funding by the Walloon region and BioWin, the health cluster for Wallonia. This is the result of a call for proposals on R&D projects in the field of Advanced Therapy Medicinal Products (ATMP). Members of the project consortium will receive €8.1M ($8.9M) in funding, including €4.7M ($5.1M) for PDC*line Pharma. The total budget is €12.5M ($13.7M). The project aims to develop PDC*neo+, a personalized therapeutic vaccine for colorectal cancer using PDC*line Pharma's innovative PDC*line technology. Targeting unique neoantigens in each colorectal cancer patient, PDC*neo+ represents a groundbreaking approach in cancer immunotherapy. Globally, colorectal cancer (CRC) is among the most prevalent and deadly cancers , with a high recurrence rate post-surgery and chemotherapy. PDC*neo+ is designed as an adjuvant treatment to prevent relapses in high-risk patients with stages II, III and certain stage IV CRCs. Its action post-chemotherapy potentially makes it a pioneering treatment in CRC. This project is a collaborative effort involving several key partners. OncoDNA contributes its expertise in personalized medicine and liquid biopsies, focusing on neoantigen identification and circulating tumor DNA analysis. salamanderU is developing a compact isolator for decentralized vaccine production to bring manufacturing closer to the clinical centers. Academic centers UCLouvain – IREC (Institut de Recherche Expérimentale et Clinique)/MIRO (Molecular Imaging, Radiotherapy and Oncology) and ULB-BCTL (Breast Cancer Translational Research Laboratory) offer essential support in translational research and clinical trial execution. The main goal of the project is to confirm the clinical feasibility and safety of PDC*neo+ in a phase I trial. This initiative is expected to have a significant impact on CRC patient care, alongside broader economic and societal benefits. Over its three-year duration, across all partners, it is estimated to create or maintain around 34 full-time jobs. “We are very happy that our project has been selected by the Walloon region. The subsidies and collaborative effort of the partners in the consortium will speed-up the launch of a first phase I clinical trial with PDC*neo+, the personalized vaccine based on PDC*line cells loaded with neoantigens to treat CRC patients, positioning our technology in the very promising field of neoantigen-based cancer vaccines,” said Eric Halioua, CEO of PDC*line Pharma. “We are very thrilled to be part of this innovative project and clinical trial. It acknowledges our recent proficiency in the discovery of neoantigens and our robust experience in liquid biopsy monitoring by detection of circulating tumor DNA (ctDNA)," said Jean-Pol Detiffe, founder and chief strategy and innovation officer at OncoDNA. “We are very enthusiastic about participating in this collaborative project and bringing the production of PDC*Neo+ closer to the patient. Through this project, salamanderU strengthens its position as a designer and manufacturer of innovative isolators for the manufacture of ATMP,” said Claude Dedry, CEO of salamanderU. “We are very pleased and motivated to take part in this exciting and collaborative project. With our expertise, we will contribute to characterizing the immunogenicity of colorectal cancers and to the development and recruitment of patients for this clinical trial,” said Marc Van den Eynde and Jean-Pascal Machiels, oncologists at UCLouvain (Cliniques universitaires St-Luc). “We are delighted to be involved in this interesting collaborative project. Leveraging our expertise in various ‘omics’ technologies, such as single-cell RNA sequencing and spatial transcriptomics, we will delve into the tumor microenvironment of colorectal cancers. Our objective is to develop predictive biomarkers for vaccine response and actively contribute to patient recruitment for the clinical trial," said Christos Sotiriou, head of the BCTL at ULB and Francesco Sclafani, gastrointestinal oncologist and clinical researcher at Institut Jules Bordet, Hopital Universitaire de Bruxelles (HUB) and Bordet Cancer Research Laboratory. About PDC*line Pharma Founded in 2014 as a spin-off of the French Blood Bank (EFS), PDC*line Pharma is a Belgian-French clinical-stage biotech company that develops an innovative class of active immunotherapies for cancers, based on a GMP-grade allogeneic therapeutic cell line of Plasmacytoid Dendritic Cells (PDC*line). PDC*line is much more potent than conventional dendritic cell-based vaccines in priming and boosting antitumor antigen-specific cytotoxic T-cells, including the T-cells specific for neoantigens, and is synergistic with checkpoint inhibitors. The technology can potentially be applied to any type of cancer. Following a first-in-human phase I feasibility study in melanoma, PDC*line Pharma is now focused on the development of PDC*lung01, its candidate for Non-Small-Cell Lung Cancer (NSCLC), currently in phase I/II trials, and PDC*neo with neoantigens, in preclinical development. The company has a staff of 42, with an experienced management team. It has raised more than €61M in equity and non-dilutive funding. In March 2019, PDC*line Pharma granted the LG Chem Life Sciences company an exclusive license in South Korea and an exclusive option in other Asian countries for the development and commercialization of the PDC*lung01 cancer vaccine for lung cancer. The total deal is worth €108M, plus tiered royalties on net sales in Asia. www.pdc-line-pharma.com About OncoDNA OncoDNA is a leading genomic and theranostic company specializing in precision medicine for the treatment of cancer and genetic diseases. The company helps clinicians, academic researchers, and biopharma companies to outsmart molecular complexity with the mission of delivering the promise of precision medicine. The company not only provides clinical guidance for the treatment and real-time monitoring of late-stage cancer patients, but also supports research and drug development in cancer and genetic diseases. Since its early days in 2012, OncoDNA grew into a corporate group of companies with world-renowned expertise. The Group offers a unique portfolio that combines NGS services, biomarker testing, data analysis software and clinical decision support tools. OncoDNA is headquartered in Belgium, and its entities – BioSequence and IntegraGen – are based in Spain and France. OncoDNA employs over 115 employees across 9 countries, works with an international network of 35 distributors and collaborates with European-based accredited laboratories. OncoDNA is keen to meet laboratory partners and oncologists who would like to benefit from our expertise and work in partnership with us for the benefit of oncologists and their patients. Visit www.oncodna.com About salamanderU salamanderU is a technology company made up of a multidisciplinary team of business experts in the life sciences, pharmaceutical engineering and IT industries. We enhance our clients’ competitive advantage by increasing the robustness and the efficiency of their operational pharmaceutical processes. salamanderU develops and commercializes both technical and digital solutions: technical with acrylic resin isolators, and digital with voice-controlled electronic batch record and manufacturing execution system software. www.salamanderu.com About UCLouvain IREC/MIRO and Cliniques universitaires Saint-Luc UCLouvain is one of the most important universities in Belgium. The IREC-MIRO-Oncology laboratory (UCLouvain) and the Cancer and Hematology Roi Albert II Institute at Cliniques universitaires Saint-Luc have expertise in clinical, translational and fundamental research in oncology. Through the conduct of several academic studies, we have characterized the tumor microenvironment of several cancers and investigated the effectiveness of different combinations of targeted and immune therapies. Our phase 1 research unit is internationally recognized in the investigation of innovative therapies such as novel immune and genetic treatments. www.uclouvain.be About IJB The Institut Jules Bordet (IJB) is the only Comprehensive Cancer Centre in Belgium and is part of the Hopital Universitaire de Bruxelles (HUB) and of the Université Libre de Bruxelles (ULB). The strength of IJB is built upon its integration of three missions: excellence of care, innovative research and a high level of education. The Institute has participated in the creation of several international networks, including the European Organization for Research and Treatment of Cancer (EORTC), the Breast International Group (BIG), Accelerating Oncology Drug Development and Innovative Strategies in Clinical Trials (Oncodistinct) and the Organization of European Cancer Institutes (OECI). The Breast Cancer Translational Research Laboratory (BCTL), headed by Prof. Sotiriou, is an academic laboratory at the ULB faculty of medicine located within the Institut Jules Bordet. The main research focus of BCTL consists of improving the molecular understanding of breast cancer biology, disease dissemination and progression using state-of-the art ‘omics’ technologies as well as identifying novel prognostic and predictive biomarkers. The ultimate goal of this laboratory is to accelerate the translation into the clinic of basic science discoveries dedicated to breast cancer. www.bordet.be

疫苗临床1期引进/卖出免疫疗法

2022-09-16

·药明康德

一周盘点 | 一文尽览18款抗癌创新疗法最新进展

▎药明康德内容团队编辑本期看点1. mRNA疫苗助力CAR-T疗法，BioNTech潜在“first-in-class” CAR-T疗法BNT211治疗睾丸癌疾病控制率（DCR）达85%。2. ImCheck Therapeutics靶向γδ T细胞的单克隆抗体疗法ICT01与检查点抑制剂（CPI）联用有潜力成为CPI耐药患者的新治疗选择。3. Relay Therapeutics高特异性FGFR2口服抑制剂RLY-4008在胆管癌患者中的早期临床数据亮眼。4. Exelixis的下一代口服酪氨酸激酶抑制剂（TKI）XL092作为单药或与CPI联用在接受过免疫治疗和/或靶向VEGF的TKI治疗的患者群体中表现出令人鼓舞的疗效和安全性。5. Immunocore现货型T细胞受体（TCR）双特异疗法IMC-F106C在多种实体瘤上展现良好的耐受性，并具有持续的疗效。药明康德内容团队整理BNT211：公布1/2期临床试验的中期数据BioNTech公布了其靶向实体瘤的新一代CAR-T疗法BNT211用于治疗复发或难治性晚期实体瘤患者的1/2期临床试验的积极中期数据。结果显示，BNT211具有令人鼓舞的抗肿瘤活性迹象，并且两个测试剂量水平的安全性仍然可控。BNT211是一款潜在“first-in-class”治疗策略，它将靶向CLDN6抗原的CAR-T疗法与表达CLDN6抗原的CARVac相结合。首先给患者输注低剂量的CLDN6靶向CAR-T疗法。然后给患者注射编码CLDN6的mRNA疫苗CARVac。这种疫苗会在抗原呈递细胞表面表达CLDN6，刺激体内CAR-T细胞的扩增。在该研究中，对21例可评估患者的疗效评估显示，最佳总缓解率（ORR）为33%， DCR为67%，包括1例完全缓解（CR）、6例部分缓解（PR）和7例疾病稳定（SD）。特别令人鼓舞的临床反应是接受第2剂量水平治疗的7例睾丸癌患者中，观察到了1例CR、3例PR和2例SD，ORR为57%，DCR为85%。正如之前报道的那样，在更高剂量的CAR-T细胞和与mRNA疫苗联合使用时，抗肿瘤活性往往更高。安全性方面，在该试验中包括细胞因子释放综合征（CRS）和剂量限制性毒性在内的不良事件是可控的。观察到1次短暂发生的1级神经毒性和1次迅速消退的3级CRS。ICT01：公布1期临床试验数据ImCheck Therapeutics公布了其靶向嗜乳脂蛋白家族成员BTN3A的单克隆抗体疗法ICT01联用pembrolizumab治疗实体肿瘤的1/2a期临床试验的第1阶段剂量递增研究的数据。ICT01靶向的BTN3A在多种实体瘤和血液癌症中高度表达，同时也表达在先天和适应性免疫细胞表面。BTN3A对激活γ9δ2 T细胞的抗癌免疫反应非常关键。ICT01通过与BTN3A结合，可以选择性激活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。此次公布的数据显示，该组合疗法对CPI耐药患者显示出广泛的抗肿瘤免疫反应和持久的疾病控制，有潜力成为这类患者的新治疗选择。所有接受治疗的患者此前至少接受过一种CPI方案并失败，42%（5/12）的黑色素瘤患者，22%（4/18）的非小细胞肺癌（NSCLC）患者，22%（2/9）的膀胱癌患者及1例（1/1）头颈部鳞状细胞癌（HNSCC）患者的疾病得到了控制。安全性方面，ICT01表现出良好且一致的安全性和耐受性特征，无剂量限制性毒性组合，与单一疗法结果一致。RLY-4008：公布1/2期临床试验的中期数据Relay Therapeutics公布了其高特异性FGFR2口服抑制剂RLY-4008在1/2期临床试验中治疗携带成纤维细胞生长因子受体2（FGFR2）变异的胆管癌和多种其他实体瘤患者的积极中期数据。RLY-4008是通过Relay公司专有技术平台对蛋白构象的动态平衡进行详细分析，而开发出对FGFR2具特异性的抑制剂。临床前研究显示，RLY-4008在癌细胞系中表现出FGFR2依赖性的抗癌活性，在缩小肿瘤的同时，对其他靶标（包括FGFR家族的其他蛋白）影响极小，具有良好的抗脱靶特性。此外，RLY-4008在细胞和体内临床前模型中，表现出对已知耐药突变的强力活性。该临床试验中，17例关键剂量下的疗效可评估的胆管癌患者中，15例观察到了PR，ORR为88%。在所有剂量水平的方案中，38例未接受过泛FGFR治疗并携带FGFR2融合的胆管癌患者有资格进行疗效评估，其中24例达到了PR，ORR为63%。大多数治疗中出现的不良事件是可预测的低级别、可监测、可管理且很大程度上可逆的不良事件。未观察到4/5级不良事件。未见显著的FGFR2脱靶毒性，例如高磷血症和腹泻。XL092：公布1b期临床试验数据Exelixis公布了其下一代口服TKI XL092作为单药或与atezolizumab或avelumab联合用于无法手术的局部晚期或转移性实体瘤患者的全球开放标签1b期临床试验的结果。XL092单药和XL092与atezolizumab联用在接受过免疫治疗和/或靶向VEGF的TKI治疗的患者群体中表现出令人鼓舞的疗效和安全性。XL092可抑制与癌症生长和扩散有关的受体酪氨酸激酶的活性，包括VEGF受体、MET、AXL 和MER。这些受体酪氨酸激酶参与正常细胞功能和病理过程，例如肿瘤发生、转移、肿瘤血管生成和对多种疗法（包括免疫检查点抑制剂）的抗性。XL092单药队列的患者最常见的癌症类型是透明细胞肾细胞癌（RCC）、转移性去势抵抗性前列腺癌（CRPC）和乳腺癌。观察到71%的患者肿瘤缩小，客观缓解率为10%， DCR为90%，4例患者达到确认的PR。在接受过免疫治疗和/或靶向VEGF的TKI治疗的19例透明细胞RCC患者（68%接受过卡博替尼治疗）中，客观缓解率为11%，DCR为95%。XL092 联合atezolizumab队列的患者最常见的癌症类型是结直肠癌、转移性CRPC和肉瘤。观察到56%的患者的肿瘤缩小，客观缓解率为4%，DCR为74%，1例患者达到确认的PR。安全性方面，60%接受XL092单药治疗的患者和38%接受联合治疗的患者发生了3/4级治疗相关的不良事件（AE），未报告5级治疗相关AE。IMC-F106C：公布1期临床试验数据Immunocore公布了其现货型TCR双特异疗法的临床1期试验初步结果。数据显示IMC-F106C双特异性蛋白在多种实体瘤上展现良好的耐受性，并具有持续的疗效。IMC-F106C是一种抗癌免疫动员单克隆TCR（ImmTAC）分子，被设计用于以超高亲和力识别细胞内的癌抗原，并通过与CD3受体结合，激活效应T细胞选择性地杀死这些癌细胞。IMC-F106C靶向PRAME抗原，这是一种黑色素瘤细胞高度表达的肿瘤相关抗原。IMC-F106C是该公司开发的首个PRAMExCD3 ImmTAC。在临床活性剂量组队列当中，在以下不同实体瘤患者中观察到PR情形：皮肤黑色素瘤（2/6）、卵巢瘤（2/4）、未经tebentafusp治疗的葡萄膜黑色素瘤（3/6）。所有的卵巢瘤患者皆具铂类药物抗性，而所有皮肤黑色素瘤患者之前皆曾接受过PD-1与CTLA-4抗体治疗。在这7位达到PR的病患中，有6位仍呈现缓解状态，且其中2位已呈现缓解超过7个月。此外，大多数能够接受循环肿瘤DNA（ctDNA）检验的患者，其ctDNA含量至少出现50%的下降。安全性方面，IMC-F106C耐受性良好，治疗相关不良事件多为可控且与已知的机制一致。最常见的治疗相关不良事件为1级的CRS（没有观察到3级或以上的CRS），这些不良事件多在病患接受最初3剂治疗时发生，没有病患因此死亡或中断治疗。DS-7300：公布1/2期临床试验数据第一三共（Daiichi Sankyo）公布了其潜在的“first-in-class”靶向B7-H3的抗体偶联药物（ADC）DS-7300在针对实体肿瘤的1/2期临床试验中的后续数据。B7-H3在多种癌症类型中过度表达，包括肺癌、前列腺癌和食道癌，并且其过度表达已被证明与某些癌症的不良预后相关，这使得B7-H3成为了有潜力的治疗靶点。该临床试验招募的患者的肿瘤类型包括小细胞肺癌（SCLC）、鳞状NSCLC、CRPC、食管鳞状细胞癌（ESCC）、头颈部鳞状细胞癌（HNSCC）或子宫内膜癌。在晚期肺癌患者的两个亚组中，SCLC和鳞状NSCLC患者的缓解率分别为58%和40%。SCLC患者的中位缓解持续时间（DOR）为5.5个月，鳞状NSCLC患者为4.3个月。在转移性CRPC患者中观察到33%的缓解率，中位DOR为4.4个月。在ESCC患者中观察到23%的缓解率，中位DOR为2.8个月。BCA101：公布1/1b期临床试验数据Bicara Therapeutics公布了其潜在“first-in-class”EGFRxTGF-β双特异性抗体BCA101的1/1b期临床试验的新数据。BCA101的一端可以与癌症细胞表面的EGFR受体结合，另一端是TGF-β陷阱。TGF-β在构建具有免疫抑制能力的肿瘤微环境中起到重要作用，通过捕获TGF-β，这款疗法可能改变肿瘤微环境，帮助增强免疫细胞的抗癌活性。该1/1b期研究中，BCA101单药以及与pembrolizumab联用作为不可切除、复发/转移性HNSCC患者的一线治疗，以及作为既往接受过化疗的晚期肛管鳞状细胞癌（SCAC）患者的二线治疗进行评估。此次公布的数据显示，BCA101作为单一药物具有良好的耐受性和临床活性。在剂量递增试验中，剂量超过1000 mg队列中可评估患者的DCR为58%。在联合剂量递增试验中，13例可评估的患者中4例（31%）为PR，其中HNSCC和SCAC各2例，1例HNSCC患者对抗PD-1治疗和西妥昔单抗耐药。DCR为69%。PDC*lung01：公布1/2期临床试验的初步数据PDC*line Pharma公布了其用于NSCLC的治疗性现货肿瘤疫苗候选药物PDC*lung01单药或与抗PD-1治疗联用的1/2期临床试验的初步结果。浆细胞样树突状细胞（PDC）系是一种有效的专业抗原呈递细胞系，能够激发和增强患者的抗肿瘤细胞毒性CD8+ T细胞，并能与抗PD-1治疗协同作用。PDC*lung01是由7种活性组分组成的细胞悬液，装载着多种肿瘤抗原。此次公布的数据显示，PDC*lung01与pembrolizumab联用一线治疗IV期（转移性）NSCLC患者的客观缓解率为66.7%，9个月时的无进展生存（PFS）率为66.7%，安全性可接受。Vimseltinib：公布1/2期临床试验数据Deciphera Pharmaceuticals公布了其高选择性的CSF1R激酶抑制剂vimseltinib用于治疗不适合手术的腱鞘巨细胞瘤（TGCT）患者的1/2期研究的最新结果。结果显示，第一阶段的客观缓解率为69%，第二阶段中队列A的客观缓解率53%，队列B为46%。此外，2期研究中患者报告的疼痛和僵硬的改善具有临床意义。此次更新的安全性和有效性数据支持正在进行的3期MOTION研究。FORE8394：公布1/2a期临床试验中期数据Fore Biotherapeutics公布了其新型下一代选择性BRAF抑制剂FORE8394在BRAF激活变异的晚期肿瘤患者中的1/2a期临床试验的中期数据。FORE8394旨在靶向广泛的BRAF突变，同时保留不影响野生型RAF的活性。研究结果显示，在未使用过MAPK抑制剂的BRAF V600+人群中确认的单药ORR为43%，中位反应持续时间为17.8个月；71%的患者的临床获益超过24周。此外，在包括高级别和低级别胶质瘤在内的原发性中枢神经系统肿瘤中也观察到了FORE8394的疗效。安全性方面，FORE8394具有良好的耐受性，任何不良事件都是短暂且可控的。ANV419：公布1/2期临床试验数据Anaveon公布了其选择性IL-2激动剂ANV419在实体瘤患者中的1/2期研究的最新临床数据。研究结果显示，ANV419在高剂量下具有良好的耐受性和安全性，具有强大的药效学作用和出色的IL-2R-β-γ选择性。在ANV419的剂量≥108 µg/kg时，75%的患者至少达到疾病稳定（5例SD，1例PR）。一例仍在接受ANV419治疗的患者在治疗两周后达到PR，肿瘤体积缩小31%，到治疗3个月时，反应持续加深，肿瘤缩小56%。该药的2期项目已在黑色素瘤患者中启动，包括多发性骨髓瘤在内的多项联合试验正在准备中。TG6002：公布1期临床试验数据Transgene公布了其新一代多功能溶瘤病毒TG6002联合口服非细胞毒性前药5-氟胞嘧啶（5-FC）在晚期胃肠道癌患者中的1期临床试验的数据。TG6002被设计为能够通过引起免疫原性细胞死亡直接和选择性地破坏癌细胞（溶瘤），并通过FCU1基因直接在肿瘤中产生化疗剂。该基因在肿瘤细胞中的表达能够使5-FC局部转化为常用的化疗药物5-氟尿嘧啶（5-FU）。此次公布的1期最高剂量水平下治疗的37例患者产生的新数据表明，TG6002具有良好的耐受性，并证实了其静脉给药的作用机制。DCC-3116：公布1期临床试验数据Deciphera Pharmaceuticals公布了其潜在“first-in-class”强效、选择性的小分子ULK1/2激酶抑制剂DCC-3116单独或联合MAPK通路抑制剂用于治疗携带RAS或RAF基因突变的晚期或转移性肿瘤患者的1期剂量递增试验的数据。DCC-3116旨在通过抑制负责启动自噬的ULK1/2激酶来抑制癌症自噬，从而影响肿瘤细胞的存活。此次公布的数据显示，DCC-3116的耐受性良好，未观察到剂量限制性毒性或与治疗相关的严重不良事件。该研究中最常见的癌症类型是结直肠癌（56%）和胰腺癌（28%），83%的患者携带KRAS突变，17%携带BRAF突变。在第16周时，可评估的14例患者的最佳响应为SD，DCR为29%。Visugromab：公布1期临床试验数据CatalYm公布了其GDF-15中和抗体visugromab与PD-1抑制剂nivolumab联合用于治疗最后一线抗PD-1/PD-L1复发/难治性实体肿瘤患者的1期临床试验数据。总体而言，在最高的两个剂量水平组中观察到了25%的肿瘤消退率。在第3-5剂量水平组中的18例患者中有6例显示出临床获益，包括3例已确认的的PR和3例长期SD。其中一些患者仍在接受治疗，有的已超过12个月。此外，该试验还确定了潜在可用于选择viugromab治疗的最佳目标人群的预测性生物标志物。当回顾性地应用这些生物标志物时，PR率高达50%，临床获益率>65%。研究人员正在准备对这些发现进行验证性的临床探索。Ubamatamab：公布1/2期临床试验数据Regeneron Pharmaceuticals公布了其针对复发性卵巢癌的MUC16xCD3靶向双特异性抗体ubamatamab的1/2期临床试验的数据。在该试验中，不同剂量组的ORR为14%（6/42），在没有内脏转移的患者中，ORR为21%（6/29），在MUC16高表达的患者中，ORR为31%（4/13）。REGN5093：公布1/2期临床试验数据Regeneron Pharmaceuticals公布了其针对MET变异的晚期NSCLC患者的METxMET靶向双特异性抗体REGN5093的1/2期临床试验的数据。在接受迄今为止最高剂量测试的36例MET变异的晚期NSCLC患者中，6例达到了PR，其中5例为先前接受过抗PD-1抗体治疗的患者。Fianlimab：公布1期临床试验数据Regeneron Pharmaceuticals公布了其LAG-3抑制剂fianlimab联用PD-1抑制剂cemiplimab治疗晚期黑色素瘤的1期临床试验的数据。此次公布的数据包括3个剂量扩展队列。其中，前2个队列招募的是既往未接受过PD-1/PD-L1抑制剂治疗的患者，客观缓解率分别为62.5%和65%，第1个队列的中位无进展生存期（PFS）为24个月。第3个个队列招募的是既往接受过PD-1/PD-L1抑制剂治疗的患者，客观缓解率为 13%。Rhenium-186 NanoLiposome：公布1期临床试验数据Plus Therapeutics公布了其靶向放射疗法Rhenium-186 NanoLiposome用于治疗复发性胶质母细胞瘤（GBM）的1期临床试验数据。Rhenium-186 NanoLiposome是一种利用特殊开发的小分子与放射性同位素铼-186进行药物装载，然后固定到纳米脂质体内部的药物。在给药后，铼会释放β粒子辐射，精确地靶向快速分裂的癌细胞，而不影响周围的健康细胞和组织，同时释放γ粒子辐射，使医生能够对整个治疗过程进行实时成像。数据表明，直接给予该疗法对复发性胶质母细胞瘤患者是安全的，辐射剂量>100 Gray的患者的中位总生存期（OS）为22.9个月，辐射剂量<100 Gray的患者的中位OS为5.6 个月，总体生存获益具有统计学意义。药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息参考资料：[1] Fore Biotherapeutics Presents Positive Interim Data From Phase 1/2a Trial Evaluating FORE8394 in Patients With Advanced Tumors With Activating BRAF Alterations at ESMO 2022. Retrieved September 12, 2022, from https://www.businesswire.com/news/home/20220912005184/en[2] Plus Therapeutics Presents Positive Phase 1 Data from ReSPECT-GBM Clinical Trial at the European Society for Medical Oncology Congress 2022. Retrieved September 12, 2022, from https://ir.plustherapeutics.com/news-releases/news-release-details/plus-therapeutics-presents-positive-phase-1-data-respect-gbm[3] PDC*line Pharma presents first clinical results from Phase I/II trial with PDC*lung01 at ESMO 2022. Retrieved September 12, 2022, from http://pdc-line-pharma.com/news/pdcline-pharma-presents-first-clinical-results-phase-iii-trial-pdclung01-esmo-2022[4] Transgene Confirms the Potential of the Intravenous Route of its Invir.IO™ Oncolytic Viruses against Solid Tumors with TG6002 Phase I Data Presented at ESMO Congress 2022. Retrieved September 12, 2022, from https://www.transgene.fr/wp-content/uploads/Transgene_PressRelease_TG6002-ESMO-Poster_EN.pdf[5] Deciphera Pharmaceuticals, Inc. Presents Updated Phase 1/2 Data for Vimseltinib in TGCT at the European Society for Medical Oncology (ESMO) Congress 2022. Retrieved September 11, 2022, from https://investors.deciphera.com/news-releases/news-release-details/deciphera-pharmaceuticals-inc-presents-updated-phase-12-data[6] ImCheck Presents Positive Safety and Efficacy Data from the Completed Phase 1 Dose Escalation Cohort of ICT01 plus Pembrolizumab in the EVICTION Trial at ESMO Congress 2022. Retrieved September 10, 2022, from https://www.imchecktherapeutics.com/all-press-release/news/imcheck-presents-positive-safety-and-efficacy-data-from-the-completed-phase-1-dose-escalation-cohort-of-ict01-plus-pembrolizumab-in-the-eviction-trial-at-esmo-congress-2022/ s/[7] Deciphera Pharmaceuticals, Inc. Presents Initial Phase 1 Single Agent Dose Escalation Data for First-in-Class ULK Inhibitor of Autophagy, DCC-3116, at the European Society for Medical Oncology (ESMO) Congress 2022. Retrieved September 10, 2022, from https://investors.deciphera.com/news-releases/news-release-details/deciphera-pharmaceuticals-inc-presents-initial-phase-1-single[8] Bicara Therapeutics Presents New Data from Ongoing Phase 1/1b Trial of Lead First-in-Class Bifunctional Program, BCA101, at the European Society for Medical Oncology (ESMO) Congress 2022. Retrieved September 10, 2022, from https://www.bicara.com/bicara-therapeutics-presents-new-data-from-ongoing-phase-1-1b-trial-of-lead-first-in-class-bifunctional-program-bca101-at-the-european-society-for-medical-oncology-esmo-congress-2022/[9] Anaveon presents updated data from the Phase I/II study of ANV419 during the ESMO Congress 2022. Retrieved September 10, 2022, from https://anaveon.com/anaveon-presents-updated-data-from-the-phase-i-ii-study-of-anv419-during-the-esmo-congress-2022/[10] Exelixis Announces Dose-Escalation Results from the Phase 1 STELLAR-001 Trial Evaluating XL092 Alone and in Combination with an Immune Checkpoint Inhibitor in Patients with Advanced Solid Tumors at ESMO 2022. Retrieved September 10, 2022, from https://ir.exelixis.com/news-releases/news-release-details/exelixis-announces-dose-escalation-results-phase-1-stellar-001[11] BioNTech Presents Encouraging Phase 1/2 Follow-up Data for CAR-T Candidate BNT211 in Hard-To-Treat Solid Tumors at ESMO. Retrieved September 9, 2022, from https://investors.biontech.de/news-releases/news-release-details/biontech-presents-encouraging-phase-12-follow-data-car-t[12] Fianlimab (LAG-3 Inhibitor) Combined with Libtayo® (cemiplimab) Demonstrates Greater than 60% Response Rates in Two Independent Cohorts of Patients with Advanced Melanoma Naïve to PD-1 or PD-L1 Inhibitors. Retrieved September 12, 2022, from https://investor.regeneron.com/news-releases/news-release-details/positive-neoadjuvant-libtayor-cemiplimab-monotherapy-data[13] Late Breaking Data Presented at ESMO Congress 2022 Demonstrate Potential of RLY-4008 to Transform Treatment Options for Cholangiocarcinoma Patients with FGFR2-Driven Disease. Retrieved September 11, 2022, from https://ir.relaytx.com/news-releases/news-release-details/late-breaking-data-presented-esmo-congress-2022-demonstrate[14] CatalYm Demonstrates Clinical Efficacy and Tolerability in First-in-Human Phase 1 Trial for Visugromab and Nivolumab Combination. Retrieved September 10, 2022, from https://www.catalym.com/catalym-demonstrates-clinical-efficacy-and-tolerability-in-first-in-human-phase-1-trial-for-visugromab-and-nivolumab-combination/[15] NOVEL REGENERON BISPECIFIC ANTIBODIES SHOW ENCOURAGING ANTI-TUMOR ACTIVITY IN TWO ADVANCED SOLID TUMORS. Retrieved September 10, 2022, from https://investor.regeneron.com/news-releases/news-release-details/novel-regeneron-bispecific-antibodies-show-encouraging-anti[16] Immunocore presents promising initial Phase 1 data for first off-the-shelf TCR therapy targeting PRAME at the ESMO 2022 Congress. Retrieved September 9, 2022, from https://ir.immunocore.com/news-releases/news-release-details/immunocore-presents-promising-initial-phase-1-data-first-shelf[17] DS-7300 Continues to Show Promising Durable Response in Patients with Several Types of Advanced Cancer. 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