A Study of CCT301-59 CAR T Therapy in Adult Subjects With Recurrent or Refractory Solid Tumors

NCT03960060 | Terminated Phase 1

• 1 other identifier: CCT301-59-mST01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical study is to investigate the safety and tolerability of CAR modified autologous T cells (CCT301-59) in subjects with recurrent or refractory solid tumors.

Conditions

Solid Tumor; Soft Tissue Sarcoma; Gastric Cancer; Pancreatic Cancer; Bladder Cancer

Outcome Measures

Primary Outcomes (3)

• Safety of CCT301-59 CAR T cell therapy

  To observe the safety of CCT301-59 CAR positive T cells in subjects using Common Toxicity Criteria for Adverse effects (CTCAE) version 5.0.

  Up to 52 weeks

• Efficacy of CCT301-59 CAR T cell therapy

  Objective response, such as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.

  Up to 52 weeks

• Kinetics of CAR T cells

  The level of CAR T cells in the peripheral blood and persistence of CAR T cells in patients will be tested.

  Up to 52 weeks

Study Arms (1)

CCT301-59

EXPERIMENTAL

The safety and preliminary therapeutic efficacy of CCT301-59 will be evaluated for subjects with ROR2 positive biopsy in a standard 3+3 dose escalation rule. Three dose levels of CAR T will be administered in this study: 1x10\^6, 3x10\^6, 1x10\^7 CCT301-59 CAR positive T cells/kg weight, intravenous infusion.

Biological: CCT301-59

Interventions

CCT301-59 BIOLOGICAL

Collect blood from the patients and isolate peripheral blood mononuclear cells for the production of CCT301-59. Subjects will receive the conditioning chemotherapy regimen of cyclophosphamide and fludarabine for lymphodepletion during the production of CCT301-59 and then subjects will receive one dose of CCT301-59 via intravenous injection.

CCT301-59

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary to participate in the clinical study, subjects and their family members agree to sign the informed consent form and follow all trial procedures.
• Male or female subjects 18-70 years of age.
• Subjects are diagnosed as recurrent or refractory solid tumors (soft tissue sarcoma, gastric cancer, pancreatic cancer and bladder cancer) with identified unresectable advanced or metastatic tumors by radiology and histology or cytology, progression after the first line or above treatment, or intolerance to standard treatment.
• At least one measurable lesion in accordance with RECIST 1.1, the long diameter of non-lymph node lesions ≥10mm (millimeter) according to CT (computerized tomography) scan-sectional image, or the short diameter of lymph node lesions ≥15mm; the longest axis of the measurable lesion ≥10 mm in CT scan (CT scan layer ≤ 5mm); FDG PET (fluorodeoxyglucose -positron emission tomography) of the measurable lesion \> 3 SUV (standardized uptake values).
• Subjects with ROR2 positive tumor tissue: the percentage of ROR2 positive staining cells in tumor cells detected by immunohistochemistry or RNA (Ribonucleic acid) in situ hybridization is ≥ 50%. The samples could be used within one year , otherwise the sample will be re-collected for biopsy.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score is 0 to 1.
• Expected survival will be ≥ 12 weeks.
• The organ and hematopoietic functions must meet the following requirements:
• Hemoglobin (HGB)≥90 g/L (gram per litre), no blood transfusion within two weeks;
• White blood cell count (WBC) ≥ 2.5×10\^9/L;
• Absolute neutrophil count (ANC) ≥ 1.5×10\^9/L;
• Platelet count (PLT) ≥ 80×10\^9/L;
• Total bilirubin (TBIL) ≤ 3.0ng/dL or ≤ 5 ULN (Upper Limit of Normal);
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5×ULN; AST and ALT≤ 5×ULN in case the abnormal hepatic function is caused by hepatocellular carcinoma or liver metastasis from other tumors;
• Serum creatinine (Cr) ≤ 1.5×ULN; or creatinine clearance (CrCl) ≥ 50 mL/min (milliliter per minute);

You may not qualify if:

• Pregnant or breastfeeding female subjects;
• Active infection of hepatitis B, or active hepatitis C;
• Infection with HIV/AIDS (Human Immunodeficiency Virus / Acquired Immunodeficiency Syndrome);
• Other active infection with clinical significance;
• Previous diseases or concurrent diseases:
• Subjects diagnosed as serious autoimmune disease in long-term (over two months) requirement of systemic immunosuppressant (steroid), or as immune mediated symptomatic diseases including ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), autoimmune vasculitis (e.g., Wegener's granulomatosis);
• Subjects with previous diagnosis as motor neuron disease;
• Subjects with previous disease of toxic epidermal necrolysis;
• Having any mental disorder that may affect the understanding of informed consent and relevant questionnaires, including dementia, altered mental status;
• Having serious uncontrollable disease judged in the study that may affect the subjects receiving the study treatment;
• Subjects with other active malignant tumors in the past five years including basal or squamous cell skin cancer, superficial bladder cancer or in situ breast cancer who have been completely cured, and without any follow-up treatment are not included;
• Current using of systemic steroid or steroid inhalant;
• Have used of immunotherapy treatment in the past three months or PD-1 (Programmed cell death protein 1) antibody, PD-L1 (Programmed death-ligand 1) antibody, PD-L2 antibody, CD137 (tumor necrosis factor receptor superfamily member 9, 4-1BB) antibody or CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) antibody, or cell therapy.
• Allergy to immunotherapy or relevant medications;
• Meningeal metastasis or central nervous system metastasis in the last 6 months, with obvious underlying diseases of the central nervous system, and leaving obvious symptoms;

Sponsors & Collaborators

• Shanghai PerHum Therapeutics Co., Ltd.: lead
• Shanghai Zhongshan Hospital: collaborator

Study Sites (1)

Shanghai Zhongshan Hospital

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Conditions

Sarcoma; Stomach Neoplasms; Pancreatic Neoplasms; Urinary Bladder Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Yuhong Zhou

  Shanghai Zhongshan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2019
• First Posted: May 22, 2019
• Study Start: May 16, 2019
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2023
• Last Updated: October 28, 2024

Record last verified: 2021-10

Locations

CN (1)