IFNα Expressing Mesenchymal Stromal Cells for Locally Advanced/Metastatic Solid Tumors
NCT ID: NCT05699811
Last Updated: 2023-04-28
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
40 participants
INTERVENTIONAL
2023-02-23
2026-12-31
Brief Summary
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Detailed Description
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Interferon(IFN) has been widely used for cancer treatment for its pleiotropic antitumor effects. IFN receptor signals mediate intrinsic and extrinsic effects on tumor cells and the TME, including tumor-infiltrating lymphocytes as well as tumor-associated stroma. Additionally, IFNs also exert direct intrinsic antitumor effects including inhibition of cell proliferation by inducing cell cycle arrest, cell death via apoptosis and ferroptosis, cell differentiation, and senescence, thus acting as a tumor suppressor. Accumulating evidence suggests that IFNs play critical roles in cancer immunotherapy, however, the variations in responses and the adverse effects have reduced their popularity in clinical applications. New IFN-based strategies should be considered as a high priority.
Our team has developed a protocol to genetically express IFNα in bone marrow-derived MSCs. In vitro and in vivo experiments have shown that the MSC-IFNα cells possess a potent ability to home to TME and to secret IFNα. By changing TME, MSC-IFNα induces strong anti-tumor effects in several cancer types in animal models. In addition, preliminary data also indicated that the combination of IFNα-MSCs with chemotherapy and/or programmed death-1(PD-1)/programmed death-ligand 1(PD-L1)blockade may bring an even stronger anti-tumor immunity.
In this study, by producing MSC-IFNα cells with human umbilical-cord-derived mesenchymal stromal cells (hUC-MSCs, passage 5 to passage 7), the investigators plan to conduct a first-in-human, prospective, open-label, phase 1/2 trial to evaluate the safety and efficacy of MSC-IFNα combined with or without immunochemotherapy in patients with locally advanced/metastatic solid tumors.
\[Study design\] Phase 1 Arm 1. Safety evaluation of MSC-IFNα monotherapy A total of 3-9 subjects will be enrolled for the safety evaluation of MSC-IFNα monotherapy. All treatment-related adverse events (TRAE) will be recorded for at least 28 days after cell infusion. Subjects with any grade 3-4 TRAE that lasts for 7 days or more within the 28 days after infusion will be determined as treatment intolerance (TI).
The first 3 subjects will receive MSC-IFNα infusion 1-4 times every 4-6 weeks at a dose of 2×10\^6 cells/kg. If TI occurred in any of the 3 subjects, another 3 subjects will be enrolled and received a 70% reduced MSC-IFNα dose (i.e. 6×10\^5 cells/kg, 2x10\^5/kg, and so on) until tolerable dose (no TI in all 3 subjects) was reached.
Arm 2. Safety and efficacy evaluation of MSC-IFNα combined with immunochemotherapy.
A total of 3-9 subjects will be enrolled and receive MSC-IFNα infusion (tolerable dose determined in Arm 1) every 4-6 weeks for 4 cycles. Immunochemotherapy, namely nab-paclitaxel (125 mg/m2, 5 days before cell infusions), cyclophosphamide (200 mg/m2,4 days before cell infusions) and anti-PD-1 antibody (200mg, 7 days after infusion) will be given. From the 5th cycle, subjects will receive MSC-IFNα combined with anti-PD-1 antibody (200mg, 7 days after infusion) every 4-6 weeks for another 4 cycles for efficacy consolation. From the 9th cycle, subjects will receive anti-PD-1 antibody (200mg) alone every 3 weeks for another 4 cycles for efficacy maintenance. The safety, efficacy, and other required data will be collected and the optimized combined regimen (OCR) of MSC-IFNα and immunochemotherapy will be determined. MSC-IFNα related AE will be continuously monitored in this arm, and reduced MSC-IFNα dose will be considered if necessary.
Phase 2 A total of 10-30 subjects will be enrolled and received the OCR determined in the phase 1 of the trial. The safety, efficacy, and other required data will be collected.
During the treatment, efficacy in all subjects will be assessed at baseline and every 8 weeks thereafter until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs first.
During post-treatment follow-up, efficacy and TRAEs in all subjects will be assessed every 12 weeks until death, withdrawal of consent, loss to follow-up, or end of the study, whichever occurs first.
Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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MSC-IFNα monotherapy
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.
MSC-IFNα
MSC-IFNα form a dose of 2×10\^6 cells/kg, intravenous infusion every 4-6 weeks
MSC-IFNα combined with immunochemotherapy
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.
MSC-IFNα
MSC-IFNα form a dose of 2×10\^6 cells/kg, intravenous infusion every 4-6 weeks
Nab paclitaxel
125mg/m2, intravenous infusion every 4-6 weeks
Cyclophosphamide
200mg/m2, intravenous infusion every 4-6 weeks
Anti-PD-1 monoclonal antibody
200mg, intravenous infusion every 4-6 weeks
Interventions
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MSC-IFNα
MSC-IFNα form a dose of 2×10\^6 cells/kg, intravenous infusion every 4-6 weeks
Nab paclitaxel
125mg/m2, intravenous infusion every 4-6 weeks
Cyclophosphamide
200mg/m2, intravenous infusion every 4-6 weeks
Anti-PD-1 monoclonal antibody
200mg, intravenous infusion every 4-6 weeks
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Histopathological confirmed locally advanced or metastatic solid tumors including, but not limited to, lung cancer, breast cancer, colorectal cancer, hepatocellular carcinoma, and sarcomas.
3. 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.
4. Have at least one measurable target lesion.
5. Previous treatment must be completed for more than 4 weeks prior to the enrollment of this study.
6. Have an Eastern Cooperative Oncology Group performance status (ECOG) of 0 to 2 at the time of enrollment.
7. Have adequate organ function, which should be confirmed within 2 weeks prior to the first dose of study drugs.
8. Previous treatment with anti-PD-1/PD-L1 antibodies is allowed.
9. Ability to understand and sign a written informed consent document.
10. 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.
Exclusion Criteria
2. 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.
3. Subjects are being treated with either corticosteroid (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
4. History of psychiatric disorders including depression, suicidality, and mania.
5. History of allergy or intolerance to study drug components.
6. Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
7. 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.
8. History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
9. 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.
10. Previous or concurrent cancer within 3 years prior to treatment start.
18 Years
75 Years
ALL
No
Sponsors
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Wuxi Sinotide New Drug Discovery Institutes
UNKNOWN
Chinese PLA General Hospital
OTHER
Responsible Party
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Han weidong
Director of Biotherapeutic Department
Principal Investigators
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WeiDong Han, PhD
Role: PRINCIPAL_INVESTIGATOR
Chinsese PLA Gereral Hospital
Yufang Shi, PhD
Role: STUDY_CHAIR
Wuxi Sinotide New Drug Discovery Institutes
Locations
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Department of Biotherapeutic, Chinese PLA General Hospital
Beijing, , China
Countries
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Central Contacts
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Facility Contacts
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Related Links
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In vitro and in vivo studies of MSC-IFN-α
Other Identifiers
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CHN-PLAGH-BT-078
Identifier Type: -
Identifier Source: org_study_id
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