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

NCT03393936 | Terminated Phase 1 DMC

• 1 other identifier: CCT301-mRCC01; Phase I/II
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Renal Cell Carcinoma

Keywords

CCT301-38; CCT301-59; stage IV metastatic renal cell carcinoma; AXL; ROR2

Outcome Measures

Primary Outcomes (2)

• Phase I Safety (Incidence of adverse events defined as dose-limiting toxicities(DLT)

  Incidence of adverse events defined as dose-limiting toxicities (DLT)

  Up to 28 days from cell infusion

• Phase II Objective Response Rate

  Objective Response Rate of confirmed complete and partial remission by independent radiology review RECIST (1.1)

  Up to 9 months from cell infusion

Study Arms (2)

CCT301-59

EXPERIMENTAL

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

CCT301-38

EXPERIMENTAL

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

Interventions

CCT301-38 BIOLOGICAL

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.

CCT301-38

CCT301-59 BIOLOGICAL

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.

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:

• Men or women aged 18\~70 years old.
• Patients are diagnosed as refractory / recurrent, Stage IV renal cell carcinoma by histological method with FDG PET signal \> 3 SUV in measurable metastatic lesion.
• Patients with at least two metastatic lesions, including one measurable metastatic tumor lesion \>10 mm measurable by CT.
• 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.
• Expected survival ≥12 weeks.
• ECOG 0-1
• 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

You may not qualify if:

• Pregnant women or women in lactation.
• Active HBV or HCV infection.
• HIV/AIDS infection.
• Active infection
• Previously suffered from diseases or concurrent diseases as follows:
• 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)
• Patients with previous diagnosis as motor neuron disease caused by autoimmunity
• Patients previously suffered from toxic epidermal necrolysis (TEN)
• Patients with any mental diseases including dementia, mental status change that may impinge the understanding and performance of informed consent and related questionnaire
• Patients with severe, uncontrollable diseases judged by investigator that may hinder them receiving this treatment
• 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.
• Ongoing treatment using systemic steroid or steroid inhalants.
• Previous treatment used gene/cell therapy products.
• Previous experience of immunotherapies including CIK, DC, DC-CIK, LAK for the treatment of cancer.
• Allergic to immunotherapies or related drugs

Sponsors & Collaborators

• Shanghai PerHum Therapeutics Co., Ltd.: lead
• Shanghai Public Health Clinical Center: collaborator

Study Sites (1)

Shanghai Public Health Clinical Center

Shanghai, Shanghai Municipality, 200000, China

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Tongyu Zhu

  Shanghai Public Health Clinical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects with ROR2 positive biopsy will receive CCT301-59. Subjects with AXL positive biopsy that are ROR2 negative will receive CCT301-38.

Study Record Dates

• First Submitted: December 25, 2017
• First Posted: January 9, 2018
• Study Start: March 26, 2018
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2023
• Last Updated: October 28, 2024

Record last verified: 2021-10

Locations

CN (1)