CCT301-38 CAR-T in Patients With Relapsed or Refractory AXL Positive Sarcomas

SAR Clinical Trial

Official title:

A Phase I Trial to Assess Safety, Tolerability and Anti-tumor Activity of Autologous T Cell Modified Chimeric Antigen Receptor (CAR) (CCT301-38) in Patients With Relapsed or Refractory AXL Positive Sarcomas

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05128786
• Other study ID #: CCT301-38-SAR
• Status: Recruiting
• Phase: Phase 1
• Start date: December 30, 2021
• Est. completion date: August 15, 2025

Study information

• Verified date: April 2023
• Source: Shanghai PerHum Therapeutics Co., Ltd.
• Contact: Yuhong Zhou, M.D.
• Phone: +86-21-64041990
• Email: zhou.yuhong[@]zs-hospital.sh.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 9
• Est. completion date: August 15, 2025
• Est. primary completion date: August 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• SAR
• Sarcoma

Intervention

Biological:
• CCT301-38
Blood will be collected from subjects to isolate peripheral blood mononuclear cells for the production of CCT301-38. Subjects will receive the conditioning chemotherapy regimen of cyclophosphamide and fludarabine for lymphodepletion followed by a single or multiple dose of CCT301-38 via intravenous injection.

Locations

Country	Name	City	State
China	Zhongshan Hospital Affiliated to Fudan University	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai PerHum Therapeutics Co., Ltd.	Shanghai Zhongshan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DLT	To assess the safety and tolerability of CCT301-38 cell therapy for patients with AXL-positive (IHC 1+ or greater in =50% tumor cells) relapsed or refractory sarcomas.	28 days following infusion
Secondary	ORR	Proportion of subjects with the best overall response (BOR) of subjects with PR (partial response) and CR (complete response) as determined by local investigator using RECIST 1.1	Up to 52 weeks
Secondary	DCR	Disease control rate: The proportion of subjects with CR (complete response), PR (partial response) or SD (stable disease lasting over 6 months) as determined by local investigator using RECIST 1.1.	Up to 52 weeks
Secondary	DOR	Duration of response: The duration of time from record of response to first progression of disease as determined by RECIST 1.1 or death date not relevant to disease progression.	Up to 52 weeks
Secondary	PFS	Progression free survival: The time of disease progression by RECIST 1.1 or death since cell infusion.	Up to 52 weeks
Secondary	TEAE	Number, severity and duration of treatment of emergent adverse events (TEAEs) that occur during treatment according to NCI-CTCAE v 5.0.	Up to 52 weeks
Secondary	PK	The % of patients with detectable CCT301-38 cells in peripheral blood. [Time Frame: Up to 52 weeks]	Up to 52 weeks
Secondary	Biomarker	To evaluate the correlation of AXL biopsy score to ORR. [Time Frame: Up to 52 weeks]	Up to 52 weeks