A Phase I Open-Label, Dose-escalation Trial of Tumor Necrosis Factor Alpha and Interleukin-2 Coding Oncolytic Adenovirus (TILT-123) in Combination With Pembrolizumab in Patients With Immune Checkpoint Inhibitor Refractory Non-Small Cell Lung Cancer

This is an open label, Phase 1, dose escalation trial evaluating the safety of oncolytic adenovirus TILT-123 in combination with Pembrolizumab in patients with immune checkpoint inhibitor refractory non-small cell lung cancer.

开始日期2024-03-20

申办/合作机构

TILT Biotherapeutics Oy

[+1]

NCT05222932 / Recruiting临床1期

A Phase I Open-Label, Dose-escalation Clinical Trial of Tumor Necrosis Factor Alpha and IL-2 Coding Oncolytic Adenovirus TILT-123 and Avelumab in Solid Tumor Patients (Melanoma and SCCHN) Refractory to or Progressing After Anti-PD(L)1

This is a phase 1, dose-escalation trial evaluating the safety of oncolytic adenovirus TILT-123 in combination with avelumab in patients with advanced solid tumors refractory to or progressing after anti-PD(L)1.

开始日期2023-03-08

申办/合作机构

TILT Biotherapeutics Oy

NCT05271318 / Recruiting临床1期

A Two-part, Phase I/Ib, Open-Label, Dose-escalation Trial of Tumor Necrosis Factor Alpha and Interleukin-2 Coding Oncolytic Adenovirus (TILT-123) in Combination With Pembrolizumab (Phase I Part) and Pembrolizumab and Pegylated Liposomal Doxorubicin (Phase Ib Part) in Patients With Platinum Resistant or Refractory Ovarian Cancer.

This is an open-label, phase 1, dose-escalation, multicenter and multinational trial evaluating the safety of oncolytic adenovirus TILT-123 in combination with Pembrolizumab, or Pembrolizumab and Pegylated Liposomal Doxorubicin in patients with platinum resistant or refractory ovarian cancer.

开始日期2022-05-17

申办/合作机构

TILT Biotherapeutics Oy

[+1]

100 项与 TILT Biotherapeutics Oy 相关的临床结果

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0 项与 TILT Biotherapeutics Oy 相关的专利（医药）

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项与 TILT Biotherapeutics Oy 相关的文献（医药）

2024-09-03·Clinical cancer research : an official journal of the American Association for Cancer Research

Safety, Efficacy, and Biological Data of T-Cell–Enabling Oncolytic Adenovirus TILT-123 in Advanced Solid Cancers from the TUNIMO Monotherapy Phase I Trial

Article

作者: Jaakkola, Marjut ; Kistler, Claudia ; Juteau, Susanna ; Pellinen, Teijo ; Haybout, Lyna ; Santos, Joao M. ; Korpisaari, Riitta ; Hemminki, Akseli ; Kemppainen, Jukka ; Alanko, Tuomo ; Quixabeira, Dafne C.A. ; Jirovec, Elise ; Havunen, Riikka ; Kudling, Tatiana V. ; Pakola, Santeri A. ; Clubb, James H.A. ; Sormunen, Jorma ; Cervera-Carrascon, Victor ; van der Heijden, Mirte ; Hemmes, Annabrita ; Sorsa, Suvi ; Peltola, Katriina J.

Abstract:

Purpose::

TILT-123 (igrelimogene litadenorepvec) is an oncolytic adenovirus armed with TNFa and IL2, designed to induce T-cell infiltration and cytotoxicity in solid tumors.

Patients and Methods::

TUNIMO (NCT04695327) was a single-arm, multicenter phase I dose-escalation trial designed to assess the safety of TILT-123 in advanced solid cancers refractory to standard therapy. Patients received intravenous and intratumoral TILT-123. The primary endpoint was safety by adverse events (AE), laboratory values, vital signs, and electrocardiograms. Secondary endpoints included tumor response, pharmacokinetics, and predictive biomarkers.

Results::

Twenty patients were enrolled, with a median age of 58 years. Most prevalent cancer types included sarcomas (35%), melanomas (15%) and ovarian cancers (15%). No dose-limiting toxicities were observed. The most frequent treatment-related AEs included fever (16.7%), chills (13.0%), and fatigue (9.3%). Ten patients were evaluable for response on day 78 with RECIST 1.1, iRECIST or PET-based evaluation. The disease control rate by PET was 6/10 (60% of evaluable patients) and 2/10 by RECIST 1.1 and iRECIST(20%of evaluable patients). Tumor size reductions occurred in both injected and non-injected lesions. TILT-123 was detected in injected and non-injected tumors, and virus was observed in blood after intravenous and intratumoral injections. Treatment resulted in reduction of lymphocytes in blood, with concurrent lymphocyte increases in tumors, findings compatible with trafficking.

Conclusions::

TILT-123 was safe and able to produce antitumor effects in local and distant lesions in heavily pre-treated patients. Good tolerability of TILT-123 facilitates combination studies, several of which are ongoing (NCT04217473, NCT05271318, NCT05222932, and NCT06125197).See related commentary by Silva-Pilipich and Smerdou, p. 3649

2024-09-01·MOLECULAR THERAPY

Overcoming effector T cell exhaustion in ovarian cancer ascites with a novel adenovirus encoding for a MUC1 bispecific antibody engager and IL-2 cytokine

Article

作者: Cervera-Carrascon, Victor ; Quixabeira, Dafne C A ; Zafar, Sadia ; Kanerva, Anna ; Pakola, Santeri ; Grönberg-Vähä-Koskela, Susanna A M ; Hemminki, Akseli ; Hemminki, Otto ; Arias, Victor ; Basnet, Saru ; Santos, Joao M ; Jirovec, Elise ; Kudling, Tatiana ; Haybout, Lyna ; Clubb, James H A ; Van der Heijden, Mirte

T cell-focused cancer immunotherapy including checkpoint inhibitors and cell therapies has been rapidly evolving over the past decade. Nevertheless, there remains a major unmet medical need in oncology generally and immuno-oncology specifically. We have constructed an oncolytic adenovirus, Ad5/3-E2F-d24-aMUC1aCD3-IL-2 (TILT-322), which is armed with a human aMUC1aCD3 T cell engager and IL-2. TILT-322 treatment stimulated T cell cytotoxicity through the increased presence of granzyme B, perforin, and interferon-gamma. Additional immune profiling indicated TILT-322 increased gamma delta T cell activation and impacted other cell types such as natural killer cells and natural killer-like T cells that are traditionally involved in cancer immunotherapy. TILT-322 treatment also decreased the proportion of exhausted CD8⁺ T cells as demarked by immune checkpoint expression in ovarian ascites samples. Overall, our data showed that TILT-322 treatment led to an enhanced T cell activation and reversed T cell exhaustion translating into high antitumor efficacy when given locally or intravenously. The analysis of blood and tumors isolated from an in vivo patient-derived ovarian cancer xenograft model suggested TILT-322 mediated tumor control through improved T cell functions. Therefore, TILT-322 is a promising novel anti-tumor agent for clinical translation.

2023-12-31·Oncoimmunology

Effective intravenous delivery of adenovirus armed with TNFα and IL-2 improves anti-PD-1 checkpoint blockade in non-small cell lung cancer

Article

作者: Räsänen, Jari ; Hemminki, Otto ; Aaltonen, Eero ; Quixabeira, Dafne C A ; Havunen, Riikka ; Borenius, Kristian ; Mäyränpää, Mikko I ; Lähdeniemi, Iris A K ; Sutinen, Eva ; Santos, Joao M ; Pakola, Santeri ; Arias, Victor ; Clubb, James H A ; Cervera-Carrascon, Victor ; Verschuren, Emmy W ; Hemminki, Akseli ; Kudling, Tatiana V ; Kanerva, Anna ; Sorsa, Suvi ; Ilonen, Ilkka ; Heiniö, Camilla

Lung cancer remains among the most difficult-to-treat malignancies and is the leading cause of cancer-related deaths worldwide. The introduction of targeted therapies and checkpoint inhibitors has improved treatment outcomes; however, most patients with advanced-stage non-small cell lung cancer (NSCLC) eventually fail these therapies. Therefore, there is a major unmet clinical need for checkpoint refractory/resistant NSCLC. Here, we tested the combination of aPD-1 and adenovirus armed with TNFα and IL-2 (Ad5-CMV-mTNFα/mIL-2) in an immunocompetent murine NSCLC model. Moreover, although local delivery has been standard for virotherapy, treatment was administered intravenously to facilitate clinical translation and putative routine use. We showed that treatment of tumor-bearing animals with aPD-1 in combination with intravenously injected armed adenovirus significantly decreased cancer growth, even in the presence of neutralizing antibodies. We observed an increased frequency of cytotoxic tumor-infiltrating lymphocytes, including tumor-specific cells. Combination treatment led to a decreased percentage of immunosuppressive tumor-associated macrophages and an improvement in dendritic cell maturation. Moreover, we observed expansion of the tumor-specific memory T cell compartment in secondary lymphoid organs in the group that received aPD-1 with the virus. However, although the non-replicative Ad5-CMV-mTNFα/mIL-2 virus allows high transgene expression in the murine model, it does not fully reflect the clinical outcome in humans. Thus, we complemented our findings using NSCLC ex vivo models fully permissive for the TNFα and IL-2- armed oncolytic adenovirus TILT-123. Overall, our data demonstrate the ability of systemically administered adenovirus armed with TNFα and IL-2 to potentiate the anti-tumor efficacy of aPD-1 and warrant further investigation in clinical trials.

项与 TILT Biotherapeutics Oy 相关的新闻（医药）

2024-09-09

·PipelineReview

TILT Biotherapeutics Presents Clinical Data on TILT-123 After Fully Intravenous Delivery Regimen at ESMO 2024

Results reinforce potential to develop TILT-123 as a systemic therapy in Phase II setting HELSINKI, Finland I September 09, 2024 I TILT Biotherapeutics (TILT), a clinical-stage biotechnology company developing cancer immunotherapies, announces that it will present data at the European Society of Medical Oncology (ESMO) Congress 2024. The results further demonstrate the potential for TILT-123 as an intravenous therapy. The data presented covers the results of a Phase I clinical cohort of TILT-123 monotherapy for the treatment of advanced solid cancers (NCT04695327), demonstrating the regimen is safe, resulting in tumor transduction and immunological effects in metastases. A fully intravenous delivery regimen of TILT-123 was studied in a total of 6 patients, whose cancer types included three rectal carcinomas, gastric intestinal type carcinoma, pancreatic ductal adenocarcinoma, and liposarcoma. TILT-123 was administered twice daily, first twice a week and subsequently at 3-week intervals. Of patients evaluable by imaging by data cutoff, disease control was seen in 33% of patients with RECIST1.1 and 66% of patients with PET-based criteria. Updated data will be presented at the meeting (1). TILT Biotherapeutics’ founder and CEO, Akseli Hemminki, a cancer clinician who has personally treated hundreds of cancer patients with oncolytic viruses, said “This data presented at ESMO 2024 provides additional validation on the potential of TILT-123 as fully intravenous therapy in very difficult to treat patient population. I am also proud of our progress with two other studies investigating the fully intravenous regimen of TILT-123. We are moving according to our plan towards Phase II and making good clinical progress.” TILT-123, an oncolytic adenovirus armed with tumor necrosis factor alpha (TNFα) and interleukin-2 (IL-2), is designed to enhance the efficacy of T-cell therapies, including immune checkpoint blockade or adoptive cell transfer. TILT’s approach uses oncolytic viruses to selectively replicate in and lyse cancer cells, while simultaneously stimulating immune responses towards the tumor. References: (1) Abstract: Poster #1025P presented 14 Sep at 09:00-17:00: Notes to Editors About TILT Biotherapeutics TILT Biotherapeutics is a clinical-stage biotechnology company developing cancer therapeutics based on its proprietary oncolytic adenoviruses armed with molecules including cytokines that can activate T cells and destroy cancer cells. The company’s patented TILT ® technology can be delivered intravenously, locoregionally, or intratumorally. It modifies the tumor microenvironment and has a broader systemic effect. By making cold tumors hot, it eliminates cancer’s ability to evade immune responses, thereby enhancing T-cell therapies such as immune checkpoint inhibitors, tumor infiltrating lymphocyte (TIL) therapy, and CAR T therapies. TILT’s lead asset, TILT-123 also known as Igrelimogene litadenorepvec , is a 5/3 chimeric serotype adenovirus armed with two human cytokines: TNF alpha and IL-2. Over sixty patients have been treated in five international trials sponsored by the company with promising initial efficacy responses observed in some of the patients. The company’s pioneering approach has been recognized by industry leaders. It has two collaborations with MSD (Merck & Co., Inc., Rahway, NJ, USA) investigating TILT-123 in combination with KEYTRUDA ® (pembrolizumab) in ovarian cancer (NCT05271318) and in refractory non-small cell lung cancer (NCT06125197). The company is also collaborating with Merck KGaA (Darmstadt, Germany) and investigating TILT-123 in combination with Bavencio ® (avelumab). Based in Helsinki, Finland, and with an office in Boston, the company was established over a decade ago as a spin-out from the University of Helsinki. It has funding from Lifeline Ventures, Finnish Industry Investment (TESI), angel investors, Business Finland, the European Innovation Council, and the U.S. Department of Defense. SOURCE: TILT Biotherapeutics

临床1期免疫疗法临床结果临床2期

2024-05-28

·BioSpace

TILT Biotherapeutics Presents Clinical Data on TILT-123 in Ovarian Cancer at ASCO 2024

Results reinforce potential to develop TILT-123 as a systemic therapy HELSINKI, Finland, May 28, 2024 (GLOBE NEWSWIRE) -- TILT Biotherapeutics (TILT), a clinical-stage biotechnology company developing cancer immunotherapies, announces that it will present two abstracts at the American Society of Clinical Oncology (ASCO) Annual Meeting 2024. Abstract (5562) demonstrates promising safety and efficacy data of TILT-123 in ovarian cancer patients, whilst abstract (2658) demonstrates the potential for TILT-123 as an intravenous therapy. Abstract (5562)* covers the results of a Phase I clinical trial of TILT-123 in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA® (pembrolizumab), for the treatment of platinum-resistant or -refractory ovarian cancer, demonstrating the combination is safe and appears to induce disease control in a difficult-to-treat patient population. 14 patients (out of 15 enrolled) were evaluable for treatment response, with disease control achieved in 64.3%. Analysis of biological samples indicated the presence of TILT-123 and induction of T cells in injected and non-injected lesions. Long term survival was seen in some patients: Median progression free survival (PFS) and overall survival (OS) in all patients were 105 and 280 days. In patients with stable disease (SD) on day 92 by RECIST 1.1, median PFS was 174 days and median OS was 293 days. Abstract (2658) introduces the development of oncolytic adenovirus TILT-123 as an intravenous (IV) therapy. Results across three Phase I trials showed that IV delivery results in systemic tumor transduction and accumulation of lymphocytes at tumors. This means TILT-123 reached tumors, despite not being directly injected into them, and successfully triggered an immune system toward the cancer. The IV injection of TILT-123 results in persistence of the virus in peripheral blood for up to 7 days. Tumor transduction was observed in 75% of patients in three Phase I trials on day 8 post TILT-123 systemic administration. TILT Biotherapeutics’ founder and CEO, Akseli Hemminki, a cancer clinician who has personally treated hundreds of cancer patients with oncolytic viruses, said “This data presented at ASCO 2024 provides additional validation as we move forward in our clinical trials for patients with resistant or refractory ovarian cancer that have few other treatment options.” TILT-123, an oncolytic adenovirus armed with tumor necrosis factor alpha (TNFα) and interleukin-2 (IL-2), is designed to enhance the efficacy of T-cell therapies, including immune checkpoint blockade or adoptive cell transfer. TILT’s approach uses oncolytic viruses to selectively replicate in and lyse cancer cells, while simultaneously stimulating immune responses towards the tumor. References: Abstract (5562): Poster #433 presented 3 June at 09:00-12:00 Abstract (2658): Poster #137 presented 1 June at 09:00-12:00 *The work was supported by the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense, in the amount of $2,098,194.00, through the Ovarian Cancer Research Program under Award No. HT9425-23-1-0988. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Assistant Secretary of Defense for Health Affairs or the Department of Defense. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Notes to Editors About TILT Biotherapeutics TILT Biotherapeutics is a clinical-stage biotechnology company developing cancer therapeutics based on its proprietary oncolytic adenoviruses armed with molecules including cytokines that can activate T cells and destroy cancer cells. The company’s patented TILT® technology can be delivered intravenously, locoregionally, or intratumorally. It modifies the tumor microenvironment and has a broader systemic effect. By making cold tumors hot, it eliminates cancer’s ability to evade immune responses, thereby enhancing T-cell therapies such as immune checkpoint inhibitors, tumor infiltrating lymphocyte (TIL) therapy, and CAR T therapies. TILT’s lead asset, TILT-123 also known as Igrelimogene litadenorepvec, is a 5/3 chimeric serotype adenovirus armed with two human cytokines: TNF alpha and IL-2. About fifty patients have been treated in four international trials sponsored by the company with promising initial efficacy responses observed in some of the patients. The company’s pioneering approach has been recognized by industry leaders. It has two collaborations with MSD (Merck & Co., Inc., Rahway, NJ, USA) investigating TILT-123 in combination with KEYTRUDA® (pembrolizumab) in ovarian cancer (NCT05271318) and in refractory non-small cell lung cancer (NCT06125197). The company is also collaborating with Merck KGaA, Darmstadt, Germany, and investigating TILT-123 in combination with avelumab. Based in Helsinki, Finland, and with an office in Boston, the company was established over a decade ago as a spin-out from the University of Helsinki. It has funding from Lifeline Ventures, Finnish Industry Investment (TESI), angel investors, Business Finland, the European Innovation Council, and the U.S. Department of Defense. Media contacts TILT Biotherapeutics COO Aino Kalervo aino@tiltbio.com Scius Communications Katja Stout +447789435990 katja@sciuscommunications.com Daniel Gooch +447747875479 daniel@sciuscommunications.com

临床结果临床1期免疫疗法ASCO会议

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.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

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