CD70 Targeted CAR-T Cells in CD70 Positive Advanced/Metastatic Solid Tumors

NCT05947487 | Recruiting Phase 1

• 1 other identifier: CHN-PLAGH-BT-080
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

In this single-center, single-arm,prospective, open-label, phase 1/2 study, the safety and efficacy of autologous CD70 targeted chimeric antigen receptor modified T (CAR-T) cell therapy will be evaluated in patients with CD70 antigen positive advanced/metastatic solid tumors . In this clinical trial, at least 12 eligible patients in dose escalation period will be enrolled to receive 3 doses of CD70-CAR cell therapy according to the "3+3" principle. In dose expansion period, additional at most 21 eligible patients will be enrolled to receive CD70-CAR-T cell therapy at dose of recommended phase 2 dose(RP2D).

Conditions

Solid Tumor, Adult

Keywords

CD70; advanced or metastatic

Outcome Measures

Primary Outcomes (3)

• Incidence of treatment related adverse events

  AE is defined as any adverse medical event from the date of randomization to 12 months after CD70-CAR-T cell infusion. Among them, CRS and ICANS were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0.

  Up to 12 months since the initiation of CD70-CAR-T cell therapy.

• Incidence of dose limiting toxicities (DLTs)

  DLT was defined as CD70-CAR-T cells-related events with onset within first 28 days following infusion: The development of Grade (G) 3 or higher grade CRS lasting \> 2 weeks; All G4 non-hematologic toxicities.

  Up to 28 days since the initiation of CD70-CAR-T cell therapy

• Maximum tolerated dose (MTD)

  MTD is defined as the highest dose level of less than or equal to 2 DLT among the 6 subjects finally determined.

  Up to 28 days since the initiation of CD70-CAR-T cell therapy

Secondary Outcomes (7)

• Number and copy number of CD70-CAR-T cells

  Up to 3 years

• Objective response rate (ORR)

  Up to 3 years

• Progression Free Survival (PFS)

  Up to 3 years

• Time to response (TTR)

  Up to 3 years

• Duration of response (DOR)

  Up to 3 years

Study Arms (1)

CD70-targeting CAR-T cells

EXPERIMENTAL

Enrolled participants will be given a preconditioning regimen consisted of albumin-bound paclitaxel, cyclophosphamide and fludarabine before the infusion of CD70-CAR-T cells. Enrolled patients in this arm will be administered CD70-CAR-T cells in 3+3 based escalation manner.

Biological: CD70-targeting CAR-T cells

Interventions

CD70-targeting CAR-T cells BIOLOGICAL

Dose escalation: Dose1 (1×10\^6 cells/kg) , Dose 2(3×10\^6 cells/kg) ,Dose 3 (1×10\^7cells/kg); Dose expansion: RP2D Drug: Albumin-bound paclitaxel Administered intravenously at dose of 100-200mg/m2 on day -5; Drug: Cyclophosphamide Administered intravenously at dose of 15-30mg/kg on day -3 and day -2; Drug: Fludarabine Administered intravenously at dose of 30mg/m2 on day -3 and day -2;

CD70-targeting CAR-T cells

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 (inclusive).
• ECOG performance status ≤2 and Estimated life expectancy of more than 3 months.
• Histopathological confirmed advanced or metastatic solid tumors failed to at least first-line treatment or initially diagnosed advanced/metastatic solid tumors that have no NCCN guideline recommended standard first-line therapy. CD70 antigen expression level ≥ 30%.
• At least one measurable lesion at baseline per RECIST version 1.1.
• Fresh solid tumor samples or formalin-fixed paraffin embedded tumor archival samples within 6 months are necessary; Fresh tumor samples are preferred. Subjects are willing to accept tumor rebiopsy in the process of this study.
• Adequate organ function as defined by the following criteria: ANC≥1.5x10\^9/L; Platelet count ≥75x10\^9/L; Hemoglobin ≥90 g/L;Serum AST and serum ALT, ≤3.0 x ULN (≤5 x ULN for patients with liver cancer or metastases); Total serum bilirubin ≤1.5 x ULN(≤3 x ULN for patients with liver cancer or metastases); Serum creatinine ≤1.5 xULN or creatinine clearance of ≥60 mL/min.
• Pregnancy tests for women of childbearing age shall be negative; Both men and women agreed to use effective contraception during treatment and during the subsequent 1 year.
• Ability to understand and sign a written informed consent documen.

You may not qualify if:

• Subjects are being treated with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
• Received cytotoxic chemicals, monoclonal antibodies, or immunotherapy within 4 weeks or 5 half-lives before enrollment;
• Pregnant, lactating, or breastfeeding females;
• Known positive test result for human immunodeficiency virus (HIV) oracquired immune deficiency syndrome (AIDS);Active infection of hepatitis B virus (HBV), or hepatitis C virus (HCV);
• History of allergy or intolerance to study drug components;
• Prior organ allograft transplantations or allogeneic hematopoietic stem cell transplantation;
• Major surgery or trauma occurred within 28 days prior to enrollment, or major side effects have not been recovered.
• Known brain metastases or active central nervous system (CNS).Subjects with CNS metastases who were treated with radiotherapy for at least 3 months prior to enrollment, have no central nervous symptoms and are off corticosteroids, are eligible for enrollment, but require a brain MRI screening.
• Previous or concurrent cancer within 5 years prior to treatment start except for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors;
• Any serious underlying medical (eg, pulmonary, renal, hepatic,gastrointestinal, or neurological) or psychiatric condition or any issue that would limit compliance with study requirements;
• Vaccination within 30 days of study enrollment;
• Previously received CD70-CAR T cell therapy;
• Being participating any other trials or withdraw within 4 weeks;
• Researchers believe that other reasons are not suitable for clinical trials.

Sponsors & Collaborators

• Chinese PLA General Hospital: lead
• UTC Therapeutics Inc.: collaborator

Study Sites (1)

China

Beijing, Iotherapeutic Department of Chinsese PLA Gereral Hospital, China

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Yangbin Zhao, Ph.D

  UTC Therapeutics Inc.

  STUDY DIRECTOR

Central Study Contacts

Weidong Han, Ph.D

CONTACT

010-66937231; hanwdrsw@sina.com

Yang Liu, M.D

CONTACT

: 010-66939460; liuyang301blood@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Biotherapeutic Department

Study Record Dates

• First Submitted: July 8, 2023
• First Posted: July 17, 2023
• Study Start: July 15, 2023
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 17, 2023

Record last verified: 2023-07

Locations

CN (1)