Safety and Efficacy of CCT301 CAR-T in Adult Subjects With Recurrent or Refractory Stage IV Renal Cell Carcinoma

October 19, 2021 updated by: Shanghai PerHum Therapeutics Co., Ltd.

A Dose Escalation and Dose Expansion Trial to Assess the Safety, Tolerability and Anti-tumor Activity of Autologous T Cell Modified Chimeric Antigen Receptor (CAR) CCT 301-38 or CCT 301-59 in Patients With Recurrent or Refractory Stage IV Renal Cell Carcinoma

This is a two arm, open-label, dose escalation and dose expansion clinical study to evaluate the safety and efficacy of infusion of autologous CCT301-38 or CCT 301-59 T cells in adult subjects with relapsed and refractory stage IV metastatic renal cell carcinoma.Subjects with ROR2 positive biopsy will receive CCT301-59. Subjects with AXL positive biopsy that are ROR2 negative will receive CCT301-38.

Study Overview

Status

Active, not recruiting

Study Type

Interventional

Enrollment (Anticipated)

66

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Shanghai
      • Shanghai, Shanghai, China, 200000
        • Shanghai Public Health Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Men or women aged 18~70 years old.
  2. Patients are diagnosed as refractory / recurrent, Stage IV renal cell carcinoma by histological method with FDG PET signal > 3 SUV in measurable metastatic lesion.
  3. Patients with at least two metastatic lesions, including one measurable metastatic tumor lesion >10 mm measurable by CT.
  4. Tumor tissues samples confirmed CCT301 target positive IHC. Patient with histological biopsy.

    • tumor tissue with greater than or equal to 50% positive staining by IHC method for ROR2 ;
    • tumor tissue with greater than or equal to 50% positive staining by IHC method for AXL that is ROR2 negative.
  5. Expected survival ≥12 weeks.
  6. ECOG 0-1
  7. Adequate organ function as documented by:

    • ANC≥1.9X10^9/L
    • PLT≥100x10^9/L
    • Hb≥9.0g/dL
    • rCCR≥50ml/min
    • ALT and AST≤2.5ULN; for liver metastasis, ALT and AST ≤5ULN
    • Serum TBiL≤3.0mg/dL, TBiL≤2.5ULN
  8. PT: INR < 1.7 or extended PT to normal value < 4s
  9. Adequate venous access for venous blood collection, and no other contraindication of blood cell separation
  10. Patients with willingness to be in this study and able to provide informed consent
  11. Capable of receiving treatment and follow up, included patients are required to receive treatment in the enrolled centre
  12. Women of childbearing age are required to take acceptable measures to minimize the possibility of pregnancy during whole session. Women of childbearing age must have negative results of serum or urine tests within 24 hours prior to infusion. Women patients must not be in lactation;
  13. Immunological detection

    Exclusion Criteria:

  14. Pregnant women or women in lactation.
  15. Active HBV or HCV infection.
  16. HIV/AIDS infection.
  17. Active infection
  18. Previously suffered from diseases or concurrent diseases as follows:
  19. Patients confirmed as severe autoimmune diseases in long-term (over 2 months) need of systemic immune inhibitors (steroid) or as immune-mediated symptomatic diseases including ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), autoimmune vasculitis (for example, Wegener's granulomatosis)
  20. Patients with previous diagnosis as motor neuron disease caused by autoimmunity
  21. Patients previously suffered from toxic epidermal necrolysis (TEN)
  22. Patients with any mental diseases including dementia, mental status change that may impinge the understanding and performance of informed consent and related questionnaire
  23. Patients with severe, uncontrollable diseases judged by investigator that may hinder them receiving this treatment
  24. Patients with other previously active malignant tumors including basal or squamous skin cancer, superficial bladder cancer, and in situ breast carcinoma within 5 years who had been completely cured without the need of follow-up treatment are not excluded.
  25. Ongoing treatment using systemic steroid or steroid inhalants.
  26. Previous treatment used gene/cell therapy products.
  27. Previous experience of immunotherapies including CIK, DC, DC-CIK, LAK for the treatment of cancer.
  28. Allergic to immunotherapies or related drugs
  29. Patients in need of treatment for heart failure with ≥2 NYHA or for poor controlled hypertension.
  30. Patients with unstable or active peptic ulcer or alimentary tract hemorrhage.
  31. Patients with previous organ transplantation or ready for organ transplantation.
  32. Patients in need of anticoagulant therapy treatment (warfarin or heparin)
  33. Patients judged by investigators as not appropriate for this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CCT301-59
The safety and efficacy of CCT301-59 will be evaluated for subjects with ROR2 positive biopsy in a standard 3+3 dose escalation approach. 3 CAR T dosage will be tested in this study: 1×10^5/kg, 1×10^6/kg, 1×10^7/kg CAR+ T cells.
Subjects will undergo blood draw to isolate peripheral blood mononuclear cells (PBMCs) for the production of CCT301-59. During CCT301-59 production, subjects will receive a conditioning chemotherapy regimen of cyclophosphamide and fludarabine for the purpose of lymphocyte depletion. After lymphodepletion, subjects will receive one dose treatment with CCT301-59 by intravenous (IV) injection.
Experimental: CCT301-38
The safety and efficacy of CCT301-38 will be evaluated for subjects with AXL positive but ROR2 negative biopsy in a standard 3+3 dose escalation approach. 3 CAR T dosage will be tested in this study: 1×10^5/kg, 1×10^6/kg, 1×10^7/kg CAR+ T cells.
Subjects will undergo blood draw to isolate peripheral blood mononuclear cells (PBMCs) for the production of CCT301-38. During CCT301-38 production, subjects will receive a conditioning chemotherapy regimen of cyclophosphamide and fludarabine for the purpose of lymphocyte depletion. After lymphodepletion, subjects will receive one dose treatment with CCT301-38 by intravenous (IV) injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase I Safety (Incidence of adverse events defined as dose-limiting toxicities(DLT)
Time Frame: Up to 28 days from cell infusion
Incidence of adverse events defined as dose-limiting toxicities (DLT)
Up to 28 days from cell infusion
Phase II Objective Response Rate
Time Frame: Up to 9 months from cell infusion
Objective Response Rate of confirmed complete and partial remission by independent radiology review RECIST (1.1)
Up to 9 months from cell infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Tongyu Zhu, Shanghai Public Health Clinical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 26, 2018

Primary Completion (Anticipated)

June 30, 2022

Study Completion (Anticipated)

June 30, 2023

Study Registration Dates

First Submitted

December 25, 2017

First Submitted That Met QC Criteria

January 3, 2018

First Posted (Actual)

January 9, 2018

Study Record Updates

Last Update Posted (Actual)

October 21, 2021

Last Update Submitted That Met QC Criteria

October 19, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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