Phase I, Open-Label, Study of Tumor Infiltrating Lymphocytes Engineered With Membrane Bound IL15 Plus Acetazolamide in Adult Patients With Metastatic Melanoma

NCT05470283 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2022-0356NCI-2022-06873
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the recommended dose of OBX-115 in combination with acetazolamide that can be given to patients with metastatic melanoma previously treated with immune checkpoint inhibitors. The safety and tolerability of the study drug combination will also be studied.

Conditions

Tumor; Metastatic Melanoma; Melanoma

Outcome Measures

Primary Outcomes (1)

• Incidence and nature of dose-limiting toxicities (DLTs) during the first 28 days after OBX-115 + acetazolamide administration as assessed by CTCAE version 5.0. Incidence and severity of AEs and SAEs after OBX-115 + acetazolamide administration.

  through completion of study, an average of 1 year

Study Arms (1)

OBX-115 plus Acetazolamide

EXPERIMENTAL

Participants will receive chemotherapy to prepare your body for the study drug combination, then you will receive OBX-115 and acetazolamide.

Drug: OBX-115; Drug: Acetazolamide; Drug: Cyclophosphamide; Drug: Furosemide; Drug: Mesna; Drug: Fludarabine Phosphate

Interventions

OBX-115 DRUG

Given by IV

OBX-115 plus Acetazolamide

Acetazolamide DRUG

Given by PO

OBX-115 plus Acetazolamide

Cyclophosphamide DRUG

Given by IV

Also known as: Cytoxan®, Neosar

OBX-115 plus Acetazolamide

Furosemide DRUG

Given by IV

OBX-115 plus Acetazolamide

Mesna DRUG

Given by IV

OBX-115 plus Acetazolamide

Fludarabine Phosphate DRUG

Given by IV

Also known as: Fludarabine, Fludara

OBX-115 plus Acetazolamide

Eligibility Criteria

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

You may qualify if:

• Male or female patients age ≥ 18 at the time of signing ICF
• Patient has a pathologically confirmed diagnosis of metastatic melanoma that is unresectable stage III or stage IV and has lesion(s) amenable to resection for the generation of TILs and at least one separate lesion for RECIST v1.1 response assessment
• Patient must be relapsed and/or refractory to immune checkpoint inhibitor (ICI) therapy including either anti PD-1 either with or without anti CTLA-4 blocking antibody and/or anti LAG-3 antibody. Patients should have received standard-of-care (SOC) therapy per standard clinical practice guidelines. Patients must not have had exposure to more than 3 prior lines of anti-PD-1 antibody-containing therapeutic regimens administered in the metastatic setting If the patient is BRAF V600 mutation-positive with rapidly progressing disease, the patient should have received available FDA-approved targeted therapy.
• ECOG Performance status 0-1
• Within 7 days of tumor harvest and within 7 days of initiating lymphodepletion, patients must meet the following laboratory criteria:
• Absolute neutrophil count (ANC) ≥ 1000/mm3
• Hemoglobin ≥ 8.0 g/dL (transfusion allowed)
• Platelet count ≥ 75,000/mm3
• ALT/SGPT and AST/SGOT ≤ 2.5 x the upper limit of normal (ULN)
• Patients with liver metastases may have liver function tests (LFT) ≤ 5.0 x ULN
• Calculated creatinine clearance (Cockcroft-Gault) ≥ 50.0 mL/min
• Total bilirubin ≤ 1.5 X ULN
• Negative serum pregnancy test (female patients of childbearing potential)
• Patients must have a 12-lead electrocardiogram (EKG) showing no active ischemia and Fridericia's corrected QT interval (QTcF) less than 480 ms
• Patients must have echocardiogram showing no evidence of congestive heart failure (as defined by New York Heart Association Functional Classification III or IV) or LVEF \<50%

You may not qualify if:

• Patients with uncontrolled intercurrent medical illnesses, including active systemic infection, coagulation disorders or major cardiovascular, respiratory or immune diseases. PI or his/her designee shall make the final determination regarding appropriateness of enrollment
• Patients on chronic steroid therapy for primary immunodeficiency; however, prednisone or its equivalent is allowed at ≤ 10 mg/day
• Patients who are pregnant or breastfeeding
• Chemotherapy within 2 weeks prior to TIL harvest
• Treatment with small molecule targeted antineoplastics and chemotherapy within 2 weeks of initiation of lymphodepletion, or 5 half-lives, whichever is shorter
• The use of immune checkpoint inhibitors as bridging therapy is not allowed.
• Patients who have received live vaccines within 30 days prior to TIL harvest and initiation of lymphodepletion
• Patients with active infection requiring systemic therapy or causing fever (temperature \> 38.1oC) or patients with unexplained fever (temperature \> 38.1oC) within 7 days prior to day of investigational product administration
• Patient has active infection with human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus (HCV) requiring active antiviral therapy.
• Cytomegalovirus (CMV) IgM antibody titer or PCR assay; and Epstein-Barr virus (EBV) IgM or PCR assay indicating active infection. Tumor harvest may take place even with positive results as long as consult with infectious disease physician is planned and the infection can be appropriately treated, if needed, prior to initiation of lymphodepletion.
• Positive herpes simplex virus (HSV)-1 serology or PCR assay • Patients who are HSV PCR assay positive will need to receive appropriate treatment and become PCR assay negative prior to starting the lymphodepletion Tumor harvest may take place even with positive results as long as consult with infectious disease physician is planned and the infection can be appropriately treated, if needed, prior to initiation of lymphodepletion.
• Persistent prior therapy-related toxicities greater than Grade 2 according to Common Toxicity Criteria for Adverse Events (CTCAE) v5.0, except for peripheral neuropathy, alopecia, or vitiligo prior to enrollment. Patients with prior immune mediated hypophysitis or adrenal insufficiency or hypothyroidism are eligible for treatment as long as they are on stable, physiologic doses of hormone repletion.
• History of organ or hematopoietic stem cell transplant
• History of clinically significant autoimmune disease
• The following are exceptions to the criterion:

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Neoplasms; Melanoma

Interventions

Acetazolamide; Cyclophosphamide; Furosemide; Mesna; fludarabine phosphate; fludarabine

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Sulfanilamides; Sulfonamides; Amides; Aniline Compounds; Amines; Sulfones; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfonic Acids; Sulfur Acids

Study Officials

• Rodabe N Amaria, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

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: July 20, 2022
• First Posted: July 22, 2022
• Study Start: September 7, 2022
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

US (1)