Phase 2 Combination of Melphalan/HDS Via PHP + Tebentafusp in Treating Metastatic Uveal Melanoma

NCT ID: NCT07276386

Last Updated: 2025-12-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-31
• Study Completion Date: 2030-12-31

Brief Summary

This Phase 2 study evaluates the efficacy and safety of sequential treatment with percutaneous hepatic perfusion (PHP) using melphalan/HDS followed by tebentafusp in patients with metastatic uveal melanoma (mUM) with isolated liver metastases. The rationale is that PHP enhances antigen release and immunomodulation, potentially sensitizing tumors to tebentafusp in HLA-A*02:01-positive patients.

Conditions

Metastatic Uveal Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sequential PHP with Melphalan/HDS followed by Tebentafusp

Patients will undergo two percutaneous hepatic perfusion (PHP) procedures with melphalan/HDS, spaced 6-8 weeks apart. Tebentafusp will be initiated within 6 weeks (+/- 2 weeks) after the second PHP and administered weekly for 1 year. Additional PHP procedures (up to 6 total) may be performed as standard of care if disease progression occurs while on tebentafusp.

Group Type: EXPERIMENTAL

Melphalan/HDS (Percutaneous Hepatic Perfusion)

Intervention Type: DRUG

3 mg/kg ideal body weight (max 220 mg) infused via hepatic artery catheter.

Tebentafusp

Intervention Type: DRUG

20 mcg IV day 1, 30 mcg day 8, 68 mcg day 15, then weekly thereafter.

Interventions

Melphalan/HDS (Percutaneous Hepatic Perfusion)

3 mg/kg ideal body weight (max 220 mg) infused via hepatic artery catheter.

Intervention Type: DRUG

Tebentafusp

20 mcg IV day 1, 30 mcg day 8, 68 mcg day 15, then weekly thereafter.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patient is ≥18 years of age on the day of signing informed consent.
• ECOG performance status of 0 or 1.
• Histologically or cytologically confirmed liver metastasis of uveal melanoma.
• HLA-A*02:01 positive status.
• Measurable disease by computed tomography (CT) per RECIST 1.1 with at least one target lesion identified in the liver.
• Patient deemed suitable for PHP and tebentafusp.
• Female patient of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female patients of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 150 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Male patients of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 150 days after the last dose of study therapy. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Limited extrahepatic disease would be allowed initially, that can be treated with stereotactic body radiation therapy (SBRT) or surgical resection prior to the start of tebentafusp. This concept is similar to the FOCUS trial - definition of "treatable" limited disease at the discretion of the PI.
• Ability to provide and understand written informed consent prior to any study procedures.

• History of congestive heart failure, active cardiac conditions, including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), significant arrhythmias and severe valvular disease that precludes the use of general anesthesia.
• History or evidence of clinically significant pulmonary disease e.g. severe COPD that precludes the use of general anesthesia.
• Patients who are unable to undergo general anesthesia for any reason.
• Reduced renal function defined as Serum Creatinine >=1.5xULN or Creatinine Clearance < 40 mL/min, calculated using the Cockcroft and Gault formula.
• Reduced hepatic function (defined as AST, ALT, bilirubin>2.5*ULN and PT-INR>1.5) or medical history of liver cirrhosis (Child-Pugh Class B or C) or evidence of portal hypertension by history, endoscopy or radiology.
• Hemoglobin <90 g/L or platelets <100x109/L or neutrophils <1.5x109/L.
• Use of live vaccines four weeks before the last study treatment.
• History of severe reactions to melphalan, heparin or iodine contrast. Iodine contrast reaction history patients permitted if patient will be treated with pre-meds, or if still problematic, treating physician may switch to MRI TAP.
• Known human immunodeficiency virus (HIV) infection, acquired immunodeficiency syndrome (AIDS), hepatitis B or hepatitis C.
• Active autoimmune disease or a documented history of autoimmune disease requiring active systemic immunosuppressive treatment. Type-1 diabetes, atopic dermatitis, and hypothyroidism are exceptions to this.
• A condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Concomitant therapy with any other anti-cancer therapy, concurrent medical conditions requiring use of immunosuppressive medications (other than physiologic (i.e., >10 mg) doses of steroids or as specified in exclusion #14) or use of other investigational drugs.
• Has a known additional malignancy that is progressing or requires active treatment.
• Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 150 days after the last dose of study drug.
• A history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate in the opinion of the treating investigator.
• Previous treatment with PHP or tebentafusp.

Exclusion Criteria

• Life expectancy of less than 6 months.
• More than 50% of the liver volume replaced by tumor as measured by MRI.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Delcath Systems Inc.

INDUSTRY

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jonathan Zager, MD, FACS

Role: PRINCIPAL_INVESTIGATOR

Moffitt Cancer Center

Locations

Moffitt Cancer Center

Tampa, Florida, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Deanryan De Aquino

Role: CONTACT

Deanryan.Deaquino@moffitt.org

813-745-3998

Other Identifiers

MCC-23724

Identifier Type: -

Identifier Source: org_study_id