IFNα Expressing Mesenchymal Stromal Cells for Locally Advanced/Metastatic Solid Tumors

NCT05699811 | Recruiting Phase 1

• 1 other identifier: CHN-PLAGH-BT-078
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this first-in-human, single-center, prospective, open-label, phase 1/2 trial is to evaluate the safety and efficacy of the interferon alpha expressing mesenchymal stromal cells (MSC-IFNα) combined with or without immunochemotherapy in patients with locally advanced/metastatic solid tumors. The main questions aimed to answer are 1) to evaluate the safety and feasibility of MSC-IFNα in the treatment of locally advanced/metastatic solid tumors;2) to evaluate the anti-tumor effects of the MSC-IFNα combined with or without immunochemotherapy in the treatment of locally advanced/metastatic solid tumors; 3) to evaluate the pharmacokinetics/pharmacodynamics of MSC-IFNα and related immune effector cells.

Conditions

Locally Advanced or Metastatic Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment related adverse events(TRAE)

  Treatment related adverse events (TRAE) are defined as any medical events since the initiation of MSC-IFNα therapy. All TRAEs will be recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE V5.0)

  Up to 12 months since the initiation of MSC-IFNα therapy

Secondary Outcomes (4)

• Objective response rate (ORR) of MSC-IFNα combined with or without immunochemotherapy

  Up to 12 months since the initiation of MSC-IFNα therapy

• Progression free survival (PFS) of MSC-IFNα combined with or without immunochemotherapy

  Up to 12 months since the initiation of MSC-IFNα therapy

• Duration of response(DOR) of MSC-IFNα combined with or without immunochemotherapy

  Up to 12 months since the initiation of MSC-IFNα therapy

• Overall survival (OS) of MSC-IFNα combined with or without immunochemotherapy

  Up to 12 months since the initiation of MSC-IFNα therapy

Other Outcomes (10)

• Allograft MSC-IFNa cells in peripheral blood and in tumor microenvironments.

  Up to 12 months since the initiation of MSC-IFNα therapy

• Serum interferon-α level after infusion of MSC-IFNα

  Up to 12 months since the initiation of MSC-IFNα therapy

• Serum interferon-β level after infusion of MSC-IFNα

  Up to 12 months since the initiation of MSC-IFNα therapy

Study Arms (2)

MSC-IFNα monotherapy

EXPERIMENTAL

Subjects will be enrolled for safety evaluation of MSC-IFNα monotherapy. Subjects will receive MSC-IFNα infusion from a dose of 2×10\^6 cells/kg 1-4 times every 4-6 weeks. All treatment-related adverse events(TRAE) will be recorded for at least 28 days after the cell infusion.

Biological: MSC-IFNα

MSC-IFNα combined with immunochemotherapy

EXPERIMENTAL

Subjects will be enrolled and received MSC-IFNα combined with immunochemotherapy, namely nab-paclitaxel (125 mg/m2, 5 days before infusion), cyclophosphamide (200 mg/m2,4 days before infusion) and anti-PD-1 antibody (200mg, 7 days after infusion) for 4 cycles. From the 5th cycle, subjects will receive MSC-IFNα combined with anti-PD-1 antibody every 4-6 weeks for another 4 cycles for efficacy consolation. From the 9th cycle, subjects will receive anti-PD-1 antibody alone every 3 weeks for another 4 cycles for efficacy maintenance.

Biological: MSC-IFNα; Drug: Nab paclitaxel; Drug: Cyclophosphamide; Drug: Anti-PD-1 monoclonal antibody

Interventions

MSC-IFNα BIOLOGICAL

MSC-IFNα form a dose of 2×10\^6 cells/kg, intravenous infusion every 4-6 weeks

MSC-IFNα combined with immunochemotherapy; MSC-IFNα monotherapy

Nab paclitaxel DRUG

125mg/m2, intravenous infusion every 4-6 weeks

Also known as: Abraxane

MSC-IFNα combined with immunochemotherapy

Cyclophosphamide DRUG

200mg/m2, intravenous infusion every 4-6 weeks

MSC-IFNα combined with immunochemotherapy

Anti-PD-1 monoclonal antibody DRUG

200mg, intravenous infusion every 4-6 weeks

Also known as: Toripalimab Injection, Sintilimab Injection, Camrelizumab Injection, Tislelizumab Injection

MSC-IFNα combined with immunochemotherapy

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 locally advanced or metastatic solid tumors including, but not limited to, lung cancer, breast cancer, colorectal cancer, hepatocellular carcinoma, and sarcomas.
• Failed to at least first-line and second-line treatments or initially diagnosed locally advanced/metastatic solid tumors that have no National Comprehensive Cancer Network(NCCN) guideline-recommended therapy.
• Have at least one measurable target lesion.
• Previous treatment must be completed for more than 4 weeks prior to the enrollment of this study.
• Have an Eastern Cooperative Oncology Group performance status (ECOG) of 0 to 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 is 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 corticosteroid (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
• History of psychiatric disorders including depression, suicidality, and mania.
• 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.
• Uncontrolled concurrent 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 enrollment, and a negative result must be documented.
• Previous or concurrent cancer within 3 years prior to treatment start.

Sponsors & Collaborators

• Chinese PLA General Hospital: lead
• Wuxi Sinotide New Drug Discovery Institutes: collaborator

Study Sites (1)

Department of Biotherapeutic, Chinese PLA General Hospital

Beijing, China

RECRUITING

Related Links

• In vitro and in vivo studies of MSC-IFN-α

MeSH Terms

Interventions

Taxes; Albumin-Bound Paclitaxel; Cyclophosphamide; spartalizumab; toripalimab; sintilimab; camrelizumab; tislelizumab

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations; 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

• WeiDong Han, PhD

  Chinsese PLA Gereral Hospital

  PRINCIPAL INVESTIGATOR

• Yufang Shi, PhD

  Wuxi Sinotide New Drug Discovery Institutes

  STUDY CHAIR

Central Study Contacts

WeiDong Han, PhD

CONTACT

010-66937231; hanwdrsw@sina.com

Guanghua Rong, PhD

CONTACT

010-66947473; guanghua.rong@gmail.com

Study Design

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

Study Record Dates

• First Submitted: January 7, 2023
• First Posted: January 26, 2023
• Study Start: February 23, 2023
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 28, 2023

Record last verified: 2023-04

Locations

CN (1)