A Safety And Efficacy Study Of HLA-G- Targeted CAR-T Cells IVS-3001 In Subjects With Previously Treated Advanced HLA-G-Positive Solid Tumors

NCT05672459 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2022-0261NCI-2023-00020
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed clinical study is a Phase 1/2a trial to investigate the safety, tolerability, pharmacokinetics and clinical activity of anti-HLA-G CAR-T cells IVS-3001 administered to subjects with previously treated, locally advanced, or metastatic solid tumors which are HLA-G positive (HLA-G+) - as determined by immunohistochemistry (IHC) analysis on tumor biopsies using the 4H84 antibody.

Conditions

Solid Tumor

Keywords

IVS-3001; CART; HLA-G; ccRCC-renal cell carcinoma; Kidney cancer; EOC-epithelial ovarian cancer

Outcome Measures

Primary Outcomes (2)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  through study completion an average of 3 years.

• . Objective Response Rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

  through study completion an average of 3 years

Study Arms (1)

Dose Escalation (Part 1) and Expansion (Part 2 )

EXPERIMENTAL

Participants will receive IVS 3001 at the selected dose Participants will receive IVS 3001 at the recommended phase 2 dose

Drug: Single Injection of IVS-3001- Anti - HLA-G CAR-T cells; Drug: Fludarabine phosphate; Drug: Cyclophosphamide; Procedure: leukapheresis

Interventions

Single Injection of IVS-3001- Anti - HLA-G CAR-T cells DRUG

Given by IV (vein)

Dose Escalation (Part 1) and Expansion (Part 2 )

Fludarabine phosphate DRUG

Given by IV (vein)

Dose Escalation (Part 1) and Expansion (Part 2 )

Cyclophosphamide DRUG

Given by IV (vein)

Dose Escalation (Part 1) and Expansion (Part 2 )

leukapheresis PROCEDURE

Given by IV (vein)

Dose Escalation (Part 1) and Expansion (Part 2 )

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years old.
• Histologically or pathologically confirmed diagnosis of a locally advanced unresectable or metastatic HLA-G+ select solid tumor malignancy who failed or intolerant to standard of care therapies known to confer clinical benefit per treating physician.
• For Phase 2a, eligible subjects will be enrolled into indication-specific cohorts:
• Cohort 1: HLA-G+ clear cell renal cell carcinoma who failed or intolerant to checkpoint inhibitor (CPI) and tyrosine kinase inhibitor (TKI)
• Cohort 2: Epithelial ovarian carcinoma who failed or intolerant to platinum-based therapy, and should have failed or intolerant for PARP inhibitor if BRCA 1/2 mutated
• Cohort 3: Other HLA-G+ tumors (biomarker driven) who failed or intolerant to at least one prior line of therapy and for whom at discretion of treating physician there is no standard therapy to confer a clinical benefit
• HLA-G expression on tumor cells (any level of expression is acceptable) as determined by immunohistochemistry (IHC) analysis on tumor biopsies using the 4H84 antibody \[1, 2\]
• Measurable disease (at least one target lesion) per RECIST v1.1 \[3\]
• Life expectancy \>12 weeks.
• Availability of a pre-treatment tumor archived tissue specimen to test for HLA-G expression.
• In case an archival tissue is not available, patients should be willing to consent for pretreatment biopsy to screen for HLA-G expression.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 \[4\]
• Subjects must have adequate venous access for apheresis or agree to use of a central line for apheresis collection.
• Subject has adequate organ function:
• Cardiac: Left ventricular ejection fraction (LVEF) at rest must be \>45%.

You may not qualify if:

• Subjects who meet any of the following criteria are NOT eligible for the study.
• Immunotherapy at enrollment and after. Note: Bridging therapies (including herbal therapies) other than immunotherapies are allowed from cell harvest to 2 weeks before lymphodepletion (5 weeks for nitrosoureas or mitomycin) or 5 half-lives, whichever is shorter and must be reported in the CRF.
• Palliative radiotherapy is permitted but treatment must be completed at least 2 weeks prior to the start of lymphodepletion.
• Symptomatic, untreated, or actively progressing central nervous system metastases (subjects with prior brain metastases treated at least 2 weeks prior to the planned IVS-3001 infusion who are clinically stable and do not require chronic corticosteroid treatment are allowed.
• Primary CNS tumors.
• History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, or leptomeningeal disease.
• Ongoing toxicities related to prior anticancer therapy that have not resolved to Grade ≤ 1 (other than alopecia). Note: Current unresolved Grade ≥ 2 non-hematologic toxicity may be allowed after discussing with the study Chair/Co-Chair.
• Participation in any investigational drug study within 4 weeks prior to cell infusion.
• Autoimmune disease, chronic infection or any disease requiring systemic immunosuppressive therapy (e.g., calcineurin inhibitors, methotrexate, immunosuppressive antibodies such as anti-IL-6 or anti-IL-6-receptor).
• Prior CAR T cell or other genetically modified T cell therapy.
• Impaired cardiac function or clinically significant cardiac disease, including any of the following:
• Symptomatic congestive heart failure requiring treatment.
• Clinically significant cardiac arrhythmia.
• Uncontrolled hypertension Acute myocardial infarction or unstable angina pectoris within 6 months prior to enrollment.
• QTcF \> 480 msec; or, marked limitation of physical activity due to symptoms, or unable to carry on any physical activity without discomfort (New York Heart Association Functional Class III-IV).

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Invectys: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Kidney Neoplasms

Interventions

fludarabine phosphate; Cyclophosphamide; Leukapheresis

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques

Study Officials

• Aung Naing, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 3, 2023
• First Posted: January 5, 2023
• Study Start: June 21, 2023
• Primary Completion (Estimated): June 29, 2026
• Study Completion (Estimated): December 29, 2029
• Last Updated: February 25, 2026

Record last verified: 2026-02

Locations

US (1)