Session type: poster session
Abstract Title: A shielded CAR-T against GPC3 for refractory or relapsed hepatocellular carcinoma in China: A phase I trial
Date and time: 04/06/2021, 9:00 a.m. (EDT)
Abstract ID: 4095
Link: https://meetinglibrary.asco.org/record/199036/abstract
Revolutionary cell therapy against solid tumors
From March 10, 2021, a total of 11 patients were included in this study. All subjects had advanced HCC and had failed previous lines of treatment, including chemotherapy, TACE, and targeted therapies. All subjects had stage C (late stage) BCLC HCC, except for one stage B (intermediate stage) subject. All subjects had multiple lesions, of which 6 (54%) had distant metastases. Two subjects dropped out prematurely and were not evaluable. Of the 9 evaluable subjects, 4 achieved partial response (PR), 3 achieved stable disease (SD), and 2 experienced disease progression (PD). The objective response rate was 44.4% and the disease control rate reached 77.8%. A partial response lasting more than 6 months was observed in Subject 007 at the time of the data cutoff, whose tumor volume was reduced by more than 80% one month after the cell therapy infusion. (Dated June 2021, this subject had exceeded 8 months of disease control, follow-up is still ongoing). A good tumor response was also seen in Subject 012, who advanced and diffuses massive HCC and joined the study after failing radiation therapy, target drug, and 12 times TACE.
Barcelona Clinic Liver Cancer (BCLC) is a liver cancer staging system developed by the European Association for the Study of the Liver, to help assess patient status, select the right therapies for the right patients and predict the patient prognosis. The BCLC system classifies the HCC mainly into steps of 0, A, A1, A2, A3, A4, B, C and D.
On day 28 after infusion with CAR-T cells, the target tumor lesion had shrunk from 133 mm in diameter at baseline to 9 mm, a reduction of over 93%. Currently the subject is being evaluated for month 3 after CAR-T cell infusion, MRI has shown an almost complete tumor response. In addition, the level of AFP (alpha-fetoprotein, a tumor marker specific for primary liver cancer) decreased from a baseline of> 80,000 / ng / ml to 1148.9 ng / ml at month 1 , and 746.7 ng / ml at month 3 after infusion (normal range <40 ng / ml), demonstrating significant preliminary efficacy of Ori-CAR-001 in patients with advanced HCC.
Good security profile
Ori-CAR-001 CAR-T infusion demonstrated good safety and tolerability in 11 patients. Cytokine release syndrome (CRS) was observed in 9 patients (7 grade 1-2 cases and 2 grade 4 cases), which resolved after treatment with corticosteroids and tocilizumab. No neurotoxicity was observed.
Regarding the results of this exploratory study, Professor Ji Jiansong, Principal Investigator of Lishui Central Hospital, who is also Chief Scientist of the National Key R&D Program, Director of the Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research of Zhejiang China, said: “There is currently no effective treatment for relapsed / refractory hepatocellular carcinoma. Many challenges such as the tumor microenvironment are difficult to overcome and have limited the therapeutic effects of cell therapy in solid tumors. However, Ori-CAR-001, developed by OriginCell Therapeutics, was able to achieve an objective response rate of 44% and a disease control rate of 77% in patients with relapsed / refractory HCC, demonstrating a level of of safety and anti-tumor activity which cannot be achieved by currently available drugs Given its promising preliminary efficacy and safety data, we are confident in the future development prospects of Ori-CAR- 001 and continue our research studies. We are very proud and hope that Ori-CAR-001 will one day become a new treatment option for patients with advanced HCC.
Dr He Xiaowen, Co-Founder and Scientific Director of OriginCell Therapeutics, said, “Although immunocellular therapies have produced remarkable clinical responses in hematologic tumors, they have limited efficacy against solid tumors. OrginCell will continue to explore broader unmet needs. in this space, in the hope of bringing more effective immune-cellular therapies to clinicians and patients with advanced cancer. ”
About Ori-CAR-001
Ori-CAR-001 is a new generation autologous cell therapy with chimeric antigen receptor targeting GPC3 for the treatment of refractory / relapsed hepatocellular carcinoma (HCC). The construct of Ori-CAR-001 is composed of humanized anti-GPC3 scFv, a CD8-derived hinge region, a transmembrane domain linked to the 4-1BB co-stimulation domain, an intracellular signaling domain CD3z and Ori2 components expressed simultaneously by T2A. Compared to conventional CAR-T cells, Ori-CAR-001 has a significantly higher proportion of memory T stem cells, which can result in improved expansion and persistence in the body, thereby increasing their anti-tumor activity.
It should be noted that in addition to preliminary safety and efficacy data for Ori-CAR-001 presented at the ASCO annual meeting in 2021, OriginCell and study researchers also conducted translational medicine studies, in which the mode of administration, dosage, PK / La MP and biomarkers were explored. This will further promote the application and development of cell therapy for solid tumors.
OriginCell will plan more clinical development programs to further explore the potential of Ori-CAR-001 based on existing data, and the National Medical Products Administration (NPMA) application for an Investigational New Drug (IND) is currently underway. Classes.
About ASCO
With more than 40,000 members in more than 100 countries, the American Society of Clinical Oncology (ASCO) is the world’s leading academic organization for physicians and oncology professionals who care for people with cancer. Its mission is to prevent cancer and improve cancer care, and to promote the translation of research results into clinical practice. By providing access to a global network of oncology expertise, the ASCO Annual Meeting is recognized as the world’s most influential academic congress in the field of oncology.
About OriginCell Therapeutics
Founded in 2015, OriginCell Therapeutics Co., Ltd. (the Chinese name changed from “原 能 医学” to “原 启 生物” on May 25) received pre-Series A funding of nearly 100 million yuan exclusively from Qiming Venture Capital in late 2019, and the company has completed a Series A financing of more than 200 million yuan end of 2020. With the support of Qiming Venture Capital, OriginCell was separated from the OriginCell group as an innovative drug research and development asset and will focus on developing new immunotherapies for cancer treatment in the future.
Dedicated to independent innovation, OriginCell has built four innovative and synergistic proprietary technological platforms, namely Ori ™ Ab, a technological platform for the development and optimization of antibodies; Ori ™ CAR, a high memory CAR T technology platform; Ori ™ TIL, an efficient technological platform for cell expansion and culture; and Ori ™ UCAR, a universal CAR-T technology platform.
About Ori ™ Ab — Antibody Discovery Technology Platform
Ori ™ Ab is a technology platform that enables the expression of 1011 fully human antibody phage display libraries, 1012 nano-antibody libraries and adds antibody engineering capabilities. A series of higher antibody drug candidates and CAR-T cellular target antibodies have been produced from this platform.
About the Ori ™ CAR technology platform
Ori ™ CAR allows the insertion of unique signaling domains into a new and proprietary CAR construct, which dramatically improves the expansion efficiency of immune memory cells, effectively resists the stressful immune environment of solid tumors, improves ‘efficacy and persistence of CAR-T and inhibits tumor growth and prevents recurrence.
About Ori ™ TIL — A Technology Platform for Cellular Expansion and Culture
Ori ™ TIL can dramatically increase the number of expanded TIL cells, improve quality attributes and treatment parameters to break therapeutic limits. Clinical efficacy and safety can be provided by younger TIL cells which can provide enhanced anti-tumor activity.
About the Ori ™ UCAR technology platform
Ori ™ UCAR can effectively combine with antibody technology, Ori technology, gene editing and cell differentiation technology to make future CAR-T therapies more universal and convenient, while effectively reducing their cost of use.
SOURCE Organic technology Yuanqi (Shanghai) Co., Ltd.