cct301-38 car-t in patients with relapsed or refractory axl positive sarcomas

Conditions: SAR

Summary: this clinical study is to investigate the safety and tolerability of cct301-38 car modified autologous t cells (cct301-38) in subjects with relapsed or refractory axl positive sarcomas

this study is an open label, single-center phase i dose escalation trial to assess the safety, tolerability, dlt and mtd of cct301-38 cell therapy in patients with axl positive relapsed or refractory sarcomas. subjects that meet inclusion criteria with positive axl biopsy (ihc 1+ or greater in ≥50% tumor cells) will receive cct301-38 according to the 3+3 dose escalation design.

Eligibility criteria:
inclusion criteria: 1. patients with willingness to be in the study and follow all study procedures, and capable of providing informed consent 2. male or female aged 18-70 years; 3. patients with unresectable, locally advanced or metastatic relapse/refractory sarcomas that have failed at least the front line standard treatment confirmed by histology or cytology; 4. at least one measurable lesion, i.e. the length of non-lymph node lesions examined according to ct cross-sectional scanning or magnetic resonance imaging (mri), or the short diameter of the lymph node lesions is ≥15 mm according to recist 1.1, and the fdg pet signal from the measurable lesion is \> 3 suv; 5. tumors with axl positive (ihc 1+ or greater) in ≥50% of all tumor cells. a new biopsy is required if the sample is over one year. 6. ecog performance status 0-1; 7. expected survival greater than 12 weeks; 8. adequate organ and hematopoietic system functions to meet the following requirements: * hemoglobin (hgb) s 90 g/l, no blood transfusions within two weeks; * white blood cell (wbc) count≥2.5×109/l； * absolute neutrophil count (anc) ≥1.5×109/l; * platelet (plt) count ≥80×109/l; * total bilirubin (tbil) ≤3.0ng/dl or ≤5 uln; * alt and ast ≤5 uln; for liver metastasis, alt and ast ≤5 uln * creatinine (cr) ≤1.5 x uln; or creatinine removal rate (crcl) ≥50 ml/min; 9. pt: inr \< 1.7 or extended pt to normal value \< 4s 10. normal language, recognition and consciousness assessed by investigator during screening phase; 11. capable of receiving treatment and follow-up, including treatment in the clinical center; exclusion criteria: 1. females with pregnancy or in lactation period; 2. subjects with active hepatitis b, or active hepatitis c. subjects with undetectable hbv dna or hcv rna after anti-virus treatment can be enrolled; 3. hiv positive; 4. other active infections of clinical significance; 5. subjects with the following previous or accompanying diseases: • subjects diagnosed as severe autoimmune diseases that require long term (more than 2 months) treatment with systemic immunosuppressants (steroids), or diseases with immune-mediated symptoms, including ulcerative colitis, crohn's disease, rheumatoid arthritis, systemic lupus erythematosus (sle), and autoimmune vasculitis (e.g. wegena granuloma); 6. patients with previous diagnosis as motor neuron disease caused by autoimmunity; 7. patients previously suffered from toxic epidermal necrolysis (ten) 8. patients with any mental illness, including dementia, mental changes, which may cause difficulties understanding the informed consent and related questionnaires; 9. patients with serious uncontrollable diseases, which may interfere with the therapies in this study; 10. patients with other active malignancies in the past 5 years excluding those with completely cured basal or squamous skin cancers, superficial bladder cancers or primary breast cancers without need of follow-up treatment; 11. subjects receiving systemic steroids or steroid inhalants; 12. patients who have received tumor immunotherapy (including monoclonal antibody against pd-1, pd-l1, pd-l2, cd137 or ctla-4, or cell therapy) in the past 4 weeks; 13. subjects allergic to immunotherapies or related drugs; 14. patients with metastatic lesions in meninges or central nervous system, or clear evidence of central nervous system diseases with continuous significant symptoms in the last 6 months; 15. patients with nyha class ii heart failure, or hypertension incontrollable by standard care, or medical history of myocarditis, or heart attack within a year; 16. subjects who have received or are going to receive organ transplantation; 17. patients with active bleeding; 18. patients with incontrollable pleural or abdominal fluid that needs clinical treatment or intervention; 19. patients as determined by the investigators to be inappropriate for the study.

Keywords: axl, car-t, cct301-38, sarcoma car-t cct301-38 sarcoma