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

October 24, 2024 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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
66

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • China
    • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 66 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Biological: CCT301-59
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.
Biological: CCT301-38
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Shanghai PerHum Therapeutics Co., Ltd.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Shanghai Public Health Clinical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 26, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 25, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 3, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 9, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 28, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 24, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CCT301-mRCC01; Phase I/II

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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