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

Exclusion Criteria

• •1. 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.
• •2. 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.
• •3. Primary CNS tumors.
• •4. 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.
• •5. 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.
• •6. Participation in any investigational drug study within 4 weeks prior to cell infusion.
• •7. 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).
• •8. Prior CAR T cell or other genetically modified T cell therapy.
• •9. 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).
• •10. Major surgical procedure, other than for diagnosis, within 4 weeks prior to enrollment, or anticipation of the need for a major surgical procedure during the study.
• •11. Received a vaccine containing live virus within 6 weeks prior the lymphodepletion.
• •12. Treatment with systemic chronic steroid therapy (prednisone ≥ 10 mg/day or equivalent) or any other immunosuppressive therapy (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 7 days or 7 half- lives of the prescribed therapy, whichever is shorter, prior to the planned apheresis date.
• •Note:
• •* The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
• •* Patients who receive low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.
• •13. Uncontrolled intercurrent illness including but not limited to poorly controlled hypertension or diabetes, or any medical condition determined by the investigator to be a risk for enrolling in the protocol.
• •14. Untreated or active infection at the time of initial screening, within 72 hours before lymphodepletion or at the time of leukapheresis. Prior oral or IV antibiotics antifungals or antiviral medications must be completed at least 1 week prior to IVS-3001 infusion except for use of prophylactic antimicrobial agents.
• •15. Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of Screening:
• •* Active hepatitis B virus (HBV) infection (chronic or acute), defined as having a positive hepatitis B surface antigen (HBsAg) test during Screening. Subjects with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody (HBc Ab) test at screening are eligible for the study if HBV deoxyribonucleic acid (DNA) test is negative. If a subject has a negative HBsAg test and a positive total HBc Ab test at screening, an HBV DNA test should be performed HBV viral load must be less than 100 UI/mL evaluated by PCR
• •* Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test followed by a positive HCV ribonucleic acid (RNA) test during Screening. The HCV RNA test will be performed only for subjects who have a positive HCV test. If patient infected with HBV the viral load must be less than 100 UI/mL evaluated by PCR.
• •16. History of Grade ≥ 2 bleeding within 4 weeks.
• •17. Subjects with symptomatic intrinsic lung disease
• •18. Subject is a woman of child-bearing potential and is pregnant (positive serum β-human choriogonadotropin test at Baseline), planning to become pregnant within 12 months after lymphodepletion, or is breastfeeding.
• •19. Subject is a man who plans to donate sperm or father a child within 12 months after lymphodepletion.
• •20. History of second primary malignant disease with the following exceptions:
• •* Malignancies that were treated and have not recurred within 2 years prior to Screening.
• •* Completely resected basal cell or squamous cell skin cancers.
• •* Any malignancy considered to be indolent, not requiring therapy and with low metastatic potential.