Dacarbazine

近年来，随着免疫细胞疗法的兴起及逐渐惠及临床许多中晚期癌症患者常面临一个关键疑问：正在接受化疗的患者能否联合免疫细胞治疗以提升疗效？ 多项临床研究已给出明确答案：中晚期癌症患者在化疗基础上联合免疫细胞疗法（如 CAR-T、TIL、NK 细胞等），可显著增强治疗效果，尤其在延长生存期、提高缓解率及降低复发风险等方面优势显著。以下结合全球肿瘤医生网整理的不同癌种关键研究数据与机制分析，为这一联合治疗策略提供具体佐证，助力患者坚定抗癌信心，开拓治疗新选择。 结直肠癌：NK+αβT细胞联合化疗，助结直肠癌患者达完全缓解，19个月未复发 《转化癌症研究》报告了一则突破性临床案例：一名IV期结直肠癌（CRC）患者接受卡培他滨联合NK+αβT细胞治疗后，获得显著治疗响应。治疗后患者癌胚抗原（CEA）水平从14.7ng/mL骤降至1.9ng/mL（恢复至正常范围），肝脏转移灶经CT扫描显示体积显著缩小，密度趋近正常肝组织（详见下图B/C）。基于影像学评估，患者达到 完全缓解（CR） —— 治疗前最大病灶为13.44mm×10.81mm，治疗后已无法测量 。更值得关注的是， 19个月随访期间患者未出现复发迹象，且无并发症发生 。 ▼该患者肝转移灶过继免疫治疗前（图A）、治疗后（图B）CT扫描，及增强CT扫描（图C） ▲图源“TCR”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 小细胞肺癌：DC-CIK与短程化疗联合实现长期生存 小细胞肺癌发病率低，但预后不佳。广泛期小细胞肺癌患者约占所有小细胞肺癌病例的70%，中位总生存期为8-13个月，5年总生存率仅为1%-5%。 2024年6月，《Frontiers in Oncology》报告了一个“CIK 细胞联合化疗治疗广泛期小细胞肺癌患者，实现13年长期生存”的病例报告！ 该患者是一位40多岁的男性，吸烟指数400，出现反复炎性咳嗽，经检查证实右肺小细胞肺癌，并伴右肺门和纵隔淋巴结转移。于是该患者开始放疗同时应用局部放疗，该治疗方案早期效果显著，然而随着疾病的进展，患者的原发病灶出现生长，遂开始接受CIK 治疗。 幸运的是，CIK 免疫细胞治疗联合化疗 4 个月后， 肺部CT显示患者原发性肺病灶明显缩小 （详见下图B）。治疗结束后， 肺部病灶无显著进展 （详见下图C）。并在后续随访中， 病灶持续稳定。 截至2024年，他已与这种侵袭性疾病 共生存了13年 。最新的肺内影像学数据和肿瘤评估指标 提示病情稳定，原发灶和转移灶均未进展。 ▼该患者治疗前后肺部CT对比 ▲图源“frontiers”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 注： ①图A：2013年肺CT，红色箭头指示右肺病灶更进展（化疗后）。 ②图B：2013年肺CT，CIK细胞治疗联合化疗3个月后，红色箭头指示右肺病灶缩小。 ③图C：2016年肺CT，CIK细胞治疗联合化疗治疗结束后。红色箭头指示右肺病灶。 ④图D：2023年肺CT。红色箭头指示右肺病灶稳定。 黑色素瘤：TIL疗法突破免疫耐药困境 一项纳入153例晚期黑色素瘤患者的临床研究显示，TIL 疗法联合化疗（达卡巴嗪）可以明显延缓患者的生存期，甚至实现无瘤。 按照常规疗法，这些患者可能只能活七八个月。但是在接受TIL疗法之后，大部分患者都控制住了病情， 疾病控制率（DCR）为77.8%，客观缓解率（ORR）为31.4%，甚至有9位患者达到肿瘤完全缓解（CR） 。 实体瘤整体数据：辅助性免疫细胞疗法（DC、T 淋巴细胞）联合化疗等，长期生存潜力显著 2022年8月，日本医学研究团队在《ANTICANCERRESEARCH》杂志发表了一项关于"辅助性免疫细胞疗法（DC、T淋巴细胞）联合其他全身疗法治疗实体瘤"的疗效分析。该研究纳入141例实体瘤患者（涵盖肺癌、胰腺癌、乳腺癌、结直肠癌、胃癌等），采用T淋巴细胞、树突状细胞（DC）疫苗联合化疗的治疗方案。 结果显示：全部入组患者 3年、5年、10年总生存率（OS）分别达86.6%、80.9%，10年总生存率（OS）竟高达74.5% （详见下图）。其中 乳腺癌患者生存数据尤为突出：3年OS率达100%，5年OS率96.2%，10年OS率86.4% 。 此外，全部入组患者 3年、5年、10年无疾病生存率（DFS）分别为72.8%、70.5%和58.5% （详见下图），充分证实免疫细胞疗法在预防肿瘤复发方面的显著价值。 小编寄语 虽然手术、放化疗的在抗癌领域三驾马车的重要地位不容撼动，但其局限性也困扰了很多患者，比如无法避免癌症的复发或转移、因放化疗而产生的副作用也会让患者痛苦不堪。而伴随着过继性免疫细胞疗法的蓬勃发展，无论是早期亦或是中晚期癌症患者，都有了更多选择。相对于只接受手术、放疗、化疗的传统治疗，辅助细胞免疫疗法能显著提高治疗效果，延长患者的生存期，达到1+1＞2的效果！ 参考资料 [1]Liu T,et al.Long-term, 13-year survival after immune cell therapy combined with chemotherapy for extensive-stage small-cell lung cancer: a case report[J]. Frontiers in Oncology, 2024, 14: 1389725. https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1389725/full [2]Li S,et al. Significant clinical response of advanced colorectal cancer to combination therapy involving capecitabine and adoptive cell transfer therapy: a case report[J]. Translational Cancer Research, 2019, 8(2): 693. https://tcr.amegroups.org/article/view/27354/html 本文为全球肿瘤医生网原创，未经授权严禁转载

MUNICH, Germany I June 24, 2025 I Thermosome GmbH , a clinical-stage drug development company focused on targeted tumor therapies, today announced new, encouraging data from its ongoing Phase I clinical trial evaluating its lead compound THE001 (DPPG 2 -TSL-DOX) in combination with regional hyperthermia (RHT) for the treatment of soft tissue sarcomas (STS). The Phase I study is assessing the safety, pharmacokinetics (PK), and preliminary efficacy of THE001 + RHT in participants with locally advanced unresectable or metastatic STS, who have exhausted all prior treatment options, including standard doxorubicin (DOX). Despite the early stage of development and a small number of participants, signs of meaningful clinical activity have emerged. Among the heavily pre-treated participants – including patients pre-treated with DOX – the median progression-free survival (PFS) following treatment with THE001 + RHT reached 4.5 months across both dose levels (20 and 40 mg/m²). This exceeds the typical median PFS of 2.7 to 3.5 months observed with first-line DOX therapy in treatment-naïve patients at DOX doses of 75 mg/m 2 , i.e., 2-4x higher than doses of THE001 applied in the Phase I setting. At dose level 2 (40 mg/m²), the mean PFS reached 7.1 months. Two out of three participants in this dose level achieved a partial response (PR) according to Choi criteria and completed the maximum extended treatment phase of 12 cycles (~8.3 months). Notably, one participant whose tumor was initially considered unresectable, could undergo surgical resection at the end of the extended study treatment. This participant showed a tumor shrinkage of -16% in the sum of target lesions, a partial response according to Choi criteria and no vital tumor cells in the resected target lesion. Across dose levels 1 and 2, THE001 + RHT demonstrated a favorable safety profile. There were no dose-limiting toxicities or high-grade treatment-related adverse events that led to treatment discontinuation, underscoring the good tolerability of THE001 in combination with RHT. “These findings not only provide consistent proof of the galenic concept of heat-triggered, largely complete DOX release from THE001, but also demonstrate clinical benefit in a highly challenging patient population,” said Dr. Frank Hermann, Chief Medical Officer of Thermosome. “We are particularly encouraged by the results of one participant who underwent resection after 12 full treatment cycles with THE001 and regional hyperthermia with no vital tumor cells found in the resected target lesion. These results clearly support future exploration in the neoadjuvant setting.” Alexander Eggermont, Professor of Clinical and Translational Immunotherapy, University Medical Center, Utrecht, and a member of Thermosome´s Clinical Advisory Board, commented: “The Phase I data of THE001, a thermosensitive liposomal DOX, and regional hyperthermia in heavily pre-treated DOX-experienced soft tissue sarcoma patients, particularly from dose level 2, are very encouraging. These results demonstrate the clinical potential of this highly innovative approach and provide the necessary foundation for transitioning into Phase II proof-of-concept development. I am excited to support this important work and look forward to advancing this promising therapy, which has the potential to significantly improve outcomes for patients with soft tissue sarcoma, particularly in the neoadjuvant setting.” “It is exciting to see the promising results of THE001 combined with regional hyperthermia, demonstrating strong potential to address the high unmet need for better treatments for soft tissue sarcoma,” added Prof. Shreyaskumar Patel, the Robert R. Herring Distinguished Professor of Medicine and Medical Director of the Sarcoma Center at The University of Texas MD Anderson Cancer Center, Houston Texas, and a member of Thermosome’s Clinical Advisory Board. ”Expansion into Phase II, also including the U.S., would offer a much-needed validation of this new therapeutic strategy for patients with STS. I look forward to supporting the advancement of this innovative treatment option to improve outcomes for patients here in the U.S. and globally on the back of the orphan drug designation granted by the FDA.” Considering supportive feedback from the German Federal Institute for Drugs and Medical Devices (BfArM) on the development of THE001 + RHT in the neoadjuvant setting, the available data from last-line participants are intended to support further development in the neoadjuvant setting. About Thermosome Thermosome is a clinical-stage drug development company focused on targeted tumor therapy combined with immune stimulation for improved cancer therapy. At its core is a novel, proprietary tumor targeting approach that allows for significantly increased local drug concentration and improved tumor penetration to achieve improved clinical treatment efficacy. The first clinical indication for its lead drug candidate THE001 is soft tissue sarcoma, where the Company aims to improve the current standard of care (free doxorubicin). Thermosome’s approach enables targeted tumor treatment independent of specific molecular targets and covers patient populations across all chemo-sensitive tumor subtypes. More information: www.thermosome.com About THE001 Thermosome’s clinical-stage lead drug candidate THE001 is a thermosensitive liposomal formulation of the chemotherapeutic drug doxorubicin (DPPG 2 -TSL-DOX). It has a different mode of action than conventional liposomes. Thermosome’s technology enables intravascular drug release initiated by a mild heat trigger using clinically established hyperthermia devices. This results in up to 15-fold higher local drug concentrations in the tumor and aims to improve clinical treatment efficacy by creating a local boost at the desired site of action. These high local concentrations, which also reach less well perfused areas, are intended to overcome drug resistance. This effect cannot be achieved by administration of conventional doxorubicin due to systemic toxicity. Thermosome intends to further enhance treatment efficacy through an additive immune response induced by regional hyperthermia. THE001 has potential for further development in other anthracycline-sensitive solid tumors, such as breast, bladder, and ovarian cancer. THE001 has been granted Orphan Drug Designation for STS in Europe and the United States. About the Phase I Study The Phase I, open-label, interventional dose-escalation trial enrolling patients with (including DOX-) pre-treated locally advanced unresectable or metastatic STS ( NCT05858710 ) is being conducted at two German clinical sites testing THE001 at various different dose levels in initially up to 6 cycles every 3 weeks with option to extend to up to 12 cycles in participants with at least disease control. Both completed dose level (20 mg/m² and 40 mg/m²) were well tolerated and declared safe by the independent data safety monitoring board (DSMB). Primary endpoints of the study are the safety and tolerability of THE001 and the determination of the maximum tolerated dose. A secondary objective is the evaluation of anti-tumor activity. Initial clinical data were presented at the CTOS 2024 Annual Meeting ( link ). About Soft Tissue Sarcomas (STS) STS is an atypical tumor with a patient population that includes many young patients. Locally advanced STS (LA-STS) are large invasive tumors that are difficult or impossible to resect. Neoadjuvant therapy is used to shrink these tumors preoperatively to allow tumor surgery with curative intent. Free doxorubicin in combination with ifosfamide or dacarbazine has been the gold standard for neoadjuvant therapy of all chemo-sensitive LA-STS for several decades. Guidelines also recommend combining DOX-based therapy with regional hyperthermia. However, with response rates of less than 30%, there is a significant unmet need for improved treatment options. Soft tissue sarcomas occur in more than 50 different subtypes that do not share a common driver mutation, making biologic targeting more difficult than physically controlled targeting with the most active agent. SOURCE: Thermosome