Pan-T Booster Co-expressing MSLN CAR T Cell Therapy in Advanced/Metastatic Solid Tumors

NCT05693844 | Recruiting Phase 1 DMC

• 1 other identifier: CHN-PLAGH-BT-077
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

In preclinical study, investigators have demonstrated that the newly developed pan-T booster (harbouring CD40 agonist and one T cell costimulator agonist) co-expressing MSLN CAR T cell possess more powerful antitumor activity than previously reported MSLN-CAR T cells. In this clinical trial, enrolled patients receive an initial dose of pan-T booster co-expressing MSLN CAR T cells at 1×10\^6 cells/kg based on the basic principle of dose escalation design, in order to evaluate the safety, feasibility, pharmacokinetics/pharmacodynamics, and efficacy of pan-T booster co-expressing MSLN CAR T cell in vivo.

Conditions

Advanced or Metastatic Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Incidence of treatment related adverse events

  Treatment related adverse events are defined as any medical events since the initiation of MSLN targeted CAR T cell therapy . CRS or CRES will be graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria, and the others will be graded by CTCAE V5.0

  Up to 12 months since the initiation of MSLN targeted CAR T cell therapy

• Incidence of dose limiting toxicities (DLTs)

  Dose limiting toxicities are defined as MSLN targeted CAR T cell therapy related adverse events within the first 28 days that meet the following criteria: grade 3 or higher CRS or CRES, and any other grade 4 adverse events.

  Up to 28 days since the initiation of MSLN targeted CAR T cell therapy

Secondary Outcomes (6)

• Number and copy number of MSLN targeted CAR T cell

  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)

Pan-T booster co-expressing MSLN CAR T cell

EXPERIMENTAL

Before the infusion of pan-T booster co-expressing MSLN CAR T cells, all enrolled patients need to undergo conditioning chemotherapy consisting of albumin-bound paclitaxel, cyclophosphamide, and fludarabine.

Biological: Pan-T booster co-expressing MSLN CAR T cell; Drug: Albumin-bound paclitaxel; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

Pan-T booster co-expressing MSLN CAR T cell BIOLOGICAL

Starting Dose: 1×10\^6 cells/kg

Pan-T booster co-expressing MSLN CAR T cell

Albumin-bound paclitaxel DRUG

Administered intravenously at dose of 100-200mg/m2 on day -5

Pan-T booster co-expressing MSLN CAR T cell

Cyclophosphamide DRUG

Administered intravenously at a total dose of 15-30mg/kg on day -3 and day -2

Pan-T booster co-expressing MSLN CAR T cell

Fludarabine DRUG

Administered intravenously at dose of 30mg/m2/d on day -3 and day -2

Pan-T booster co-expressing MSLN CAR T cell

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 from 18 to 75 years with estimated life expectancy \>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. Mesothelin antigen expression percentage \>＝10%.
• \. Have at least one measurable target lesion.
• \. 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.
• \. Previous treatment must be completed for more than 4 weeks prior to the enrollment of this study, and subjects have recovered to \<= grade 1 toxicity.
• \. Have an Eastern Cooperative Oncology Group performance status (ECOG) of 0 or 2 at the time of enrollment.
• \. Have adequate organ function, which should be confirmed within 2 weeks prior to the first dose of study drugs.
• \. Previous treatment with anti-PD-1/PD-L1 antibodies are allowed.
• \. Ability to understand and sign a written informed consent document.
• \. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, and up to 90 days after the last dose of the drug.

You may not qualify if:

• \. Active, known or suspected autoimmune diseases.
• \. 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.
• \. Subjects are being treated with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
• \. History of severe hypersensitive reactions to other monoclonal antibodies.
• \. History of allergy or intolerance to study drug components.
• \. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
• \. History or concurrent condition of interstitial lung disease of any grade or severely impaired pulmonary function.
• \. Uncontrolled intercurrent illness, including ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (excluding insignificant sinus bradycardia and sinus tachycardia) or psychiatric illness/social situations and any other illness that would limit compliance with study requirements and jeopardize the safety of the patient.
• \. History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
• \. Pregnant or breast-feeding. Women of childbearing potential must have a pregnancy test performed within 7 days before the enrollment, and a negative result must be documented.
• \. Previous or concurrent cancer within 3 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)\].
• \. Vaccination within 30 days of study enrollment.
• \. Active bleeding or known hemorrhagic tendency.
• \. Subjects with unhealed surgical wounds for more than 30 days.
• \. Being participating any other trials or withdraw within 4 weeks.

Sponsors & Collaborators

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

Study Sites (1)

Kaichao Feng

Beijing, Beijing Municipality, 100853, China

RECRUITING

MeSH Terms

Interventions

Albumin-Bound Paclitaxel; Cyclophosphamide; fludarabine

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Yangbin Zhao, PhD

  UTC Therapeutics Inc.

  STUDY DIRECTOR

Central Study Contacts

Kaichao Feng, MD

CONTACT

+861066939460; timothyfkc@126.com

Weidong Han, PhD

CONTACT

+861066937463; hanwdrsw69@yahoo.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: December 27, 2022
• First Posted: January 23, 2023
• Study Start: January 20, 2023
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 10, 2024

Record last verified: 2024-05

Locations

CN (1)