Phase I/Ib Study of NK Expressing an Affinity-enhanced T-cell Receptor (TCR) Against the NY-ESO-1

NCT06083883 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2023-0289NCI-2023-08752
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find a recommended dose of donated NK cells that can be given along with chemotherapy to patients with advanced cancers. The safety and effects of this therapy will also be studied.

Conditions

Synovial Sarcoma; Myxoid/Round Cell Liposarcoma

Outcome Measures

Primary Outcomes (1)

• 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 1 year.

Study Arms (1)

Dose escalation - Inpatient and Outpatient

EXPERIMENTAL

Participants will be assigned to receive a dose level of NK cells based on when the participants joins the study. Up to 6 participants will be enrolled at each dose level. If no intolerable side effects are seen after the first 3-6, the next group of participants will get at higher dose. Up to 4 dose levels of NK cells will be tested. If the first dosing group shows intolerable side effects, a lower dose will be tested.

Drug: Fludarabine phosphate; Drug: NY-ESO-1 TCR/IL-15 NK; Drug: Cyclophosphamide

Interventions

Fludarabine phosphate DRUG

Given by IV (vein)

Also known as: Fludarabine, Fludara®

Dose escalation - Inpatient and Outpatient

NY-ESO-1 TCR/IL-15 NK DRUG

Given by IV (vein)

Dose escalation - Inpatient and Outpatient

Cyclophosphamide DRUG

Given by IV (vein)

Also known as: Cytoxan®, Neosar®

Dose escalation - Inpatient and Outpatient

Eligibility Criteria

• Age: 16 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with all cancer histology, with an HLA-A\*02:01, HLA-A\*02:05 or HLA-A\*02:06 positive and a positive expression of NY-ESO-1 (\>/= 50% tumor cells 2+ or 3+ by IHC) in the preenrollment tumor sample, for the dose escalation cohort. NY-ESO expression must be confirmed at MDACC prior to study entry.
• Patients with histologically confirmed synovial sarcoma (cohort 1) or myxoid/round cell liposarcoma (cohort 2), with an HLA-A\*02:01, HLA-A\*02:05 or HLA-A\*02:06 positive and a positive expression of NY-ESO-1 (\>/= 50% tumor cells 2+ or 3+ by IHC) in the pre-enrollment tumor sample, for the expansion cohorts. Archival samples will be permitted for screening. NY-ESO expression must be confirmed at MDACC prior to study entry.
• Patients must meet disease-specific eligibility criteria (see below).
• Patients must have relapsed or become refractory to standard of care treatment and must have received at least one prior line of systemic therapy including either doxorubicin and/or ifosfamide (synovial sarcoma and MRCLS) or trabectedin (MRCLS).
• Patients must have measurable disease per the RECIST v1.1 at enrollment.
• Patients must be at least 2 weeks from last cytotoxic chemotherapy at the time of first administration of lymphodepleting chemotherapy. Patients may continue tyrosine kinase inhibitors or other targeted therapies until at least 3 days prior to administration of lymphodepleting chemotherapy.
• Patients must be at least 3 months from any cell therapy for malignancy.
• Eastern Cooperative Oncology Group performance status 0-1 (Appendix A).
• Adequate organ function at screening, as defined by the following:
• Renal: Serum creatinine ≤ 1.5 mg/dL or estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration equation) ≥45 ml/min/1.73 m2
• Hepatic: alanine transaminase (ALT)/aspartate transaminase (AST) ≤ 2.5 x upper limit of normal (ULN) or ≤ 5 x ULN if documented liver metastases, total bilirubin ≤ 1.5 mg/dL or ≤ 3.0 mg/dL for patients with Gilbert's Syndrome. No history of liver cirrhosis and no ascites.
• Cardiac: Cardiac ejection fraction ≥ 50%, no clinically significant pericardial effusion as determined by echocardiogram (ECHO) or multigated acquisition (MUGA) scan, and no symptomatic cardiac disease or history of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)
• Pulmonary: No clinically significant pleural effusion (per principal investigator \[PI\] judgement), and baseline oxygen saturation ≥ 92% on room air,
• Hematological: absolute neutrophil count (ANC) ≥ 1000/mm3, platelet count ≥ 75,000/mm3, and hemoglobin ≥ 8 g/dL
• Coagulation: International normalized ratio (INR) ≤ 1.5 ULN and activated partial thromboplastin time (aPTT) ≤ 1.5 ULN. Patients on therapeutic doses of anticoagulation medication must have INR and/or aPTT ≤ the upper limit of the therapeutic range for intended use.

You may not qualify if:

• Presence of clinically significant ≥ Grade 2 toxicity from previous anticancer treatment, as determined by the PI.
• Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials for management or not responding to appropriate therapy. Note: Patients with simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
• Known Active hepatitis B or C.
• Known human immunodeficiency virus with detectable viral load.
• Presence of active neurological disorder(s).
• Active autoimmune disease within 12 months of enrollment (excluding low-grade psoriasis or well-controlled autoimmune thyroid disease).
• Amyloidosis or POEMS syndrome.
• Symptomatic or uncontrolled central nervous system involvement or signs of cord compression.
• In the case radiation therapy is indicated, the washout must be at least 14 days.
• Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using corticosteroids for at least 7 days prior to trial treatment.
• Patients must not have any other malignancies within the past 2 years except for in situ carcinoma of any site, adequately treated (without recurrence post resection or post radiotherapy) carcinoma of the cervix or basal or squamous cell carcinomas of the skin, or active non-lifethreatening second malignancy that would not, in the investigator's opinion, potentially interfere with the patient's ability to participate and/or complete this trial. Examples include but are not limited to: urothelial cancer Grade Ta or T1 and adenocarcinoma of the prostate treated by active surveillance.
• Presence of any other serious medical condition that may endanger the patient at investigator's discretion, including but not limited to:
• New York Heart Association Class III or IV heart failure
• Myocardial infarction or stroke ≤ 26 weeks prior to NY-ESO-1 TCR/IL-15 NK cell infusion
• Unstable angina within ≤ 13 weeks prior to NY-ESO-1 TCR/IL-15 NK cell infusion unless the underlying disease has been corrected by procedural intervention (e.g., stent, bypass)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Sarcoma, Synovial; Liposarcoma, Myxoid

Interventions

fludarabine phosphate; fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Liposarcoma; Neoplasms, Adipose Tissue

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• John Livingston, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John Livingston, MD

CONTACT

(713) 792-3626; jalivingston@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: October 9, 2023
• First Posted: October 16, 2023
• Study Start: March 27, 2024
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2028
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

US (1)