Clinical Study of Cord Blood-Derived CAR-NK Cells in Gastric Cancer and Pancreatic Cancer

Gastric Cancer Clinical Trial

Official title:

A Phase I Clinical Study of Cord Blood-Derived CAR-NK Cells Targeting Claudin18.2 in the Treatment of Advanced Gastric Cancer and Advanced Pancreatic Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06464965
• Other study ID #: 2024-105
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 13, 2024
• Est. completion date: June 2027

Study information

• Verified date: June 2024
• Source: Zhejiang Provincial People's Hospital
• Contact: Liu Yang, M.D.
• Phone: 13666601475
• Email: yangliuqq2003[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Main Objective: To study the maximum tolerated dose (MTD) and dose-dependent toxicity (DLT) of cord blood-derived CAR-NK cells (CB CAR-NK182) targeting Claudin18.2 in patients with advanced gastric cancer and advanced pancreatic cancer.

Secondary Objective: To evaluate the efficacy of CB CAR-NK182 in patients with advanced gastric cancer and advanced pancreatic cancer: overall objective tumor response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), etc.

To evaluate the CAR-NK amplification and persistence of CB CAR-NK182 in the blood of patients with advanced gastric cancer and advanced pancreatic cancer;

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: June 2027
• Est. primary completion date: June 13, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Male or female aged 18-75 years (inclusive);

2. Understands and voluntarily signs a written informed consent form, and is willing and able to comply with all trial requirements;

3. Patients with advanced gastric cancer and advanced pancreatic cancer confirmed by histopathology or cytology, who have failed standard treatment or cannot tolerate standard treatment, including but not limited to: pancreatic cancer and gastric cancer;

4. Immunohistochemical (IHC) detection of CLDN18.2, the positive expression of CLDN18.2 in tumors must be = 10%;

5. At least 1 measurable lesion according to RECIST 1.1;

6. ECOG score is 0-1;

7. All toxic reactions caused by previous antineoplastic therapy were resolved to grade 0-1 (according to NCI CTCAE 5.0 edition); Expected survival = 12 weeks;

In addition to the primary disease, no serious hematology, heart and lung, liver and kidney disease, laboratory tests meet the following requirements:

Peripheral blood neutrophil absolute value = 2000/mm3, platelet = 50000/mm3 Serum creatinine = 1.5mg/dL;ALT (alanine aminotransferase)/AST (aspartate aminotransferase) below 2.5 times the upper limit of normal; Total bilirubin = 1.5mg/dL; Cardiac ejection fraction (EF)= 50%; International standard ratio (INR) or prothrombin time (PT) below 1.5 times the upper limit of normal; Activated partial coagulation time (aPTT) below 1.5 times the upper limit of normal; 10. Women of childbearing potential must have a negative serum pregnancy test and agree to effective birth control during the treatment phase and within 12 months after injection of CAR-NK cells; Male patients must agree to use effective birth control during the study and for 12 months after injection of CAR-NK cells.

Exclusion Criteria:

1. History of other tumors;

2. Patients who have received CAR-T,CAR-NK,TCR-T and other cell therapy targeting Claudin18.2 within 3 months before study treatment;

3. Patients with hypersensitivity to cell therapy or any related drugs;

4. Active autoimmune diseases;

5. Active infections that cannot be controlled;

6. HIV infection, uncontrolled HBV, HCV and syphilis infections;

7. Have metastatic disease of the central nervous system (CNS), leptomeningeal disease or spinal cord compression;

8. Patients with severe heart disease;

9. Patients with unstable/active ulcers or bleeding from the digestive system;

10. Patients with a history of bleeding or bleeding tendency in the digestive system;

11. Pregnant or lactating women;

12. There are other factors that the researcher believes are not suitable for participating in the trial.

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastric Cancer
• Pancreas Adenocarcinoma
• Stomach Neoplasms

Intervention

Biological:
• CB CAR-NK182
To study the maximum tolerated dose (MTD) and dose-dependent toxicity (DLT) of cord blood-derived CAR-NK cells (CB CAR-NK182) targeting Claudin18.2 in patients with advanced gastric cancer and advanced pancreatic cancer

Locations

Country	Name	City	State
China	Zhejiang Provincial People's Hospital	Hangzhou	Zhejiang

Sponsors (3)

Lead Sponsor	Collaborator
Zhejiang Provincial People's Hospital	Hangzhou RonGu Biotechnology Limited Company, Zhejiang University

Country where clinical trial is conducted

China, 

References & Publications (10)

Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Ruschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. doi: 10.1016/S0140-6736(10)61121-X. Epub 2010 Aug 19. Erratum In: Lancet. 2010 Oct 16;376(9749):1302. — View Citation

Cappell KM, Kochenderfer JN. Long-term outcomes following CAR T cell therapy: what we know so far. Nat Rev Clin Oncol. 2023 Jun;20(6):359-371. doi: 10.1038/s41571-023-00754-1. Epub 2023 Apr 13. — View Citation

Fanotto V, Cordio S, Pasquini G, Fontanella C, Rimassa L, Leone F, Rosati G, Santini D, Giampieri R, Di Donato S, Tomasello G, Silvestris N, Pietrantonio F, Battaglin F, Avallone A, Scartozzi M, Lutrino ES, Melisi D, Antonuzzo L, Pellegrino A, Torri V, Aprile G. Prognostic factors in 868 advanced gastric cancer patients treated with second-line chemotherapy in the real world. Gastric Cancer. 2017 Sep;20(5):825-833. doi: 10.1007/s10120-016-0681-6. Epub 2016 Dec 27. — View Citation

Gowrikumar S, Singh AB, Dhawan P. Role of Claudin Proteins in Regulating Cancer Stem Cells and Chemoresistance-Potential Implication in Disease Prognosis and Therapy. Int J Mol Sci. 2019 Dec 20;21(1):53. doi: 10.3390/ijms21010053. — View Citation

Heinemann V, Ebert MP, Laubender RP, Bevan P, Mala C, Boeck S. Phase II randomised proof-of-concept study of the urokinase inhibitor upamostat (WX-671) in combination with gemcitabine compared with gemcitabine alone in patients with non-resectable, locally advanced pancreatic cancer. Br J Cancer. 2013 Mar 5;108(4):766-70. doi: 10.1038/bjc.2013.62. Epub 2013 Feb 14. — View Citation

Khawar MB, Gao G, Rafiq M, Shehzadi A, Afzal A, Abbasi MH, Sheikh N, Afzal N, Ashraf MA, Hamid SE, Shahzaman S, Kawish N, Sun H. Breaking down barriers: The potential of smarter CAR-engineered NK cells against solid tumors. J Cell Biochem. 2023 Aug;124(8):1082-1104. doi: 10.1002/jcb.30460. Epub 2023 Aug 11. — View Citation

Kyuno D, Takasawa A, Takasawa K, Ono Y, Aoyama T, Magara K, Nakamori Y, Takemasa I, Osanai M. Claudin-18.2 as a therapeutic target in cancers: cumulative findings from basic research and clinical trials. Tissue Barriers. 2022 Jan 2;10(1):1967080. doi: 10.1080/21688370.2021.1967080. Epub 2021 Sep 5. — View Citation

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020 Jan;70(1):7-30. doi: 10.3322/caac.21590. Epub 2020 Jan 8. — View Citation

Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, Song C, Wu H, Eng-Wong J, Kim K, Kang YK. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018 Oct;19(10):1372-1384. doi: 10.1016/S1470-2045(18)30481-9. Epub 2018 Sep 11. — View Citation

Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. doi: 10.1016/S1470-2045(17)30111-0. Epub 2017 Mar 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MTD	Maximum Tolerated Dose	3 years
Primary	DLT	Dose-Dependent Toxicity	3 years
Secondary	ORR	Overall objective tumor response rate	3 years
Secondary	DCR	Disease control rate	3 years
Secondary	PFS	progression-free survival	3 years
Secondary	OS	overall survival	3 years
Secondary	DOR	duration of response	3 years