Trial Title:
Tebentafusp-tebn With LDT in Metastatic UM
NCT ID:
NCT06626516
Condition:
Metastatic Uveal Melanoma
Conditions: Official terms:
Melanoma
Uveal Neoplasms
Molgramostim
Carmustine
Sargramostim
Conditions: Keywords:
Uveal
uveal melanoma
metastatic uveal melanoma
melanoma
Liver-directed therapy
Liver-directed
Liver
liver-directed therapies
MUM
LDT
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
Intervention model description:
Part 1A: Single-arm combination therapy (tebentafusp-tebn with hepatic IE with GM-CSF),
with the first cohort of six patients being enrolled in a safety lead in.
Part 1B: If the safety and preliminary efficacy in Part 1A are met, we will then proceed
with a randomized phase II trial. 52 patients will be randomized in a 2:1 ratio to
receive tebentafusp-tebn in combination with hepatic IE or tebentafusp-tebn alone Part 2:
Single-arm, two-stage phase II trial of sequential TACE with BCNU followed by
tebentafusp-tebn in 39 patients with higher liver tumor burden
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Tebentafusp-Tebn
Description:
Dosing: All patients enrolled in this study will receive treatment with tebentafusp-tebn
based on the approved step-up dosing regimen of 20 mcg on C1D1, 30 mcg on C1D8, then 68
mcg weekly beginning on C1D15 and thereafter. This escalated dose administered at C1D15
will be the dose used for the remainder of the treatment period unless dose reduction is
implemented for toxicity. Beginning with C1D8, tebentafusp-tebn will be administered on
the scheduled day (± 2 days), and consecutive infusions of tebentafusp-tebn must be
administered at least 5 days apart.
Arm group label:
Part 1A: Safety Lead-in
Arm group label:
Part 1B: Combination
Arm group label:
Part 1B: Tebentafusp-tebn alone
Arm group label:
Part 2: Efficacy of Combo
Other name:
kimmtrak
Other name:
IMCgp100
Intervention type:
Drug
Intervention name:
GM-CSF (Sargramostim)
Description:
Recombinant human GM-CSF (Sargramostim, Leukine®, Sanofi US) 1,500mg will be mixed with
ethiodized oil (Ethiodol®). The GM-CSF/ethiodized oil mixture will be injected
selectively into one of the hepatic lobes, followed by infusion of gelatin sponge
particles to achieve the stasis of blood flow. This will repeat every 4 weeks.
Arm group label:
Part 1A: Safety Lead-in
Arm group label:
Part 1B: Combination
Other name:
yeast-derived recombinant human GM-CSF
Other name:
Leukine
Other name:
Hepatic Immunoembolization
Other name:
GM-CSF
Other name:
Sargramostim
Intervention type:
Drug
Intervention name:
BCNU
Description:
Patients will be treated with hepatic artery infusion of 300mg BCNU (1,3-bis
[2-chloroethyl]-1-nitrosourea, Carmustine) dissolved in ethiodized oil followed by
embolization with gelatin sponge particles [TACE with BCNU 300mg]; every 4 weeks +/- 7
days in the case of either bilobar or unilobar metastasis
Arm group label:
Part 2: Efficacy of Combo
Other name:
Carmustine
Other name:
BiCNU
Other name:
bis-chloroethylnitrosourea
Other name:
Hepatic Chemoembolization
Other name:
1,3-bis [2-chloroethyl]-1-nitrosourea
Summary:
We will conduct a multicenter, open label phase I/ II trial to assess the safety and
clinical efficacy of tebentafusp-tebn in combination with liver-directed therapies in
HLA-A*0201 positive patients with metastatic uveal melanoma. In Part 1 of the study, we
will investigate the safety and efficacy of tebentafusp-tebn in combination with hepatic
IE in patients with a low to moderate hepatic disease burden. In Part 2, we will
investigate the efficacy of tebentafusp-tebn in combination with TACE in patients with
bulky hepatic disease.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥18 years of age 2. Histologically or cytologically confirmed metastatic uveal
melanoma in the liver. Patients must have at least one measurable liver metastasis
that is ≥ 10 mm in longest diameter by CT scan or MRI. Extra-hepatic disease is
allowed.
3. Tumor Size Criteria: i. Part 1: Total volume of tumor must be < 50% of the liver
involvement by CT or MRI; M1a or M1b disease with largest tumor ≤ 5 cm ii. Part 2:
M1b disease with largest tumor > 5 cm, M1c disease, or ≥ 50% liver involvement by
CT or MRI 4. No prior systemic treatment with tebentafusp-tebn 5. Prior therapy: i.
Part 1: Patients must be treatment naïve in the metastatic setting.
1. Prior surgery or ablation for oligometastatic disease is allowable.
2. Palliative radiation of non-target lesions also allowable. ii. Part 2: Patients may
have had prior systemic therapy with chemotherapy, immunotherapy, or targeted
therapy. They can also have had prior liver directed therapy including surgery,
ablation, immunoembolization, or radioembolization. However cannot have had more
than two prior lines of treatment total.
6. HLA-A*0201 positive 7. ECOG performance status or 0 or 1 at the time of screening 8.
Life expectancy of greater than 3 months as assessed by the investigator 9. Patients
must have normal organ and bone marrow function as defined below:
1. Platelet count ≥ 100,000/mm³
2. Hemoglobin > 8.0g/dL
3. AST and/or ALT < 3x upper limited of normal (ULN)
4. Total bilirubin ≤ 2.0 mg/ml
5. Note: Patients with hyperbilirubinemia clinically consistent with an inherited
disorder of bilirubin metabolism (e.g., Gilbert syndrome) will be eligible at the
discretion of the treating physician and/or the principal investigator.
6. PT/PTT < 1.5x ULN
7. Serum creatinine ≤ 2.0 mg/dl or a creatinine clearance > 60mL/min
8. Potassium, magnesium, corrected calcium, and phosphate within normal laboratory
parameters 10. Women must not be pregnant or breast-feeding. 11. Women of
child-bearing potential and men must agree to use adequate contraception (hormonal
or barrier method of birth control; abstinence) prior to study entry, for the
duration of study participation, and for the 6 months after the final dose of the
study drug. Women of child-bearing potential must have a negative serum pregnancy
test within 14 days prior to study entry. Should a woman become pregnant or suspect
she is pregnant while she or her partner is participating in this study, she should
inform her treating physician immediately.
12. Male patients treated or enrolled on this protocol must be surgically sterile
or use double barrier contraception methods from enrollment through treatment,
and for 6 months after completion of study therapy.
13. Ability to understand and the willingness to sign a written informed consent
document.
Exclusion Criteria:
Parts 1 and 2:
1. Failure to meet any of the criteria set forth in the Inclusion criteria section
2. History of prior tebentafusp-tebn use
3. Prior chemoembolization in Part 2 is not permitted
4. History of severe immediate or delayed hypersensitivity reaction to biologic drugs,
monoclonal antibodies, iodinated contrast agent
5. Presence of symptomatic liver failure including ascites and hepatic encephalopathy
6. Presence of symptomatic or untreated central nervous system (CNS) metastases, or CNS
metastases that require corticosteroids within 21 days prior to initiation of study
therapy. Patients with brain metastases may be eligible if lesions have been treated
with local therapy and there is no evidence of CNS disease progression for at least
4 weeks as measured by MRI prior to first dose of study drug
7. History of another malignancy except for: 1) those who have been disease-free for 3
years prior to study treatment; 2) patients with a history of completely resected
non-melanoma skin cancer; 3) patients with indolent secondary malignancies not
requiring active therapy; 4) patients with completely resected carcinoma in situ.
Consult the study Principal Investigator if unsure whether second malignancies meet
the requirements specified above.
8. Major surgery within 2 weeks of the first dose of study drug (minimally invasive
procedures such as bronchoscopy, tumor biopsy, insertion of a central venous access
device, and insertion of a feeding tube are not considered major surgery and are not
exclusionary)
9. Radiotherapy within 2 weeks of the first dose of study drug, with the exception of
palliative radiotherapy to a limited field, such as for the treatment of bone pain
or a focally painful tumor mass
10. No outstanding toxicities from prior therapies greater than Grade 1. Except for
prior immune related side effects such as endocrinopathy that are managed with a
stable dose of thyroid or steroid supplement.
11. Use of any investigational drugs within 28 days (or five half-lives, whichever is
shorter; with a minimum of 14 days from the last dose) preceding the first dose of
study therapy and during the study.
12. Use of hematopoietic colony-stimulating growth factors (eg. G-CSF, GMCSF, M-CSF)
within 14 days prior to study treatment initiation. An erythroid-stimulating agent
is allowed as long as it was initiated at least 2 weeks prior to the first dose of
study treatment and the patient is not red blood cell transfusion dependent.
13. Known history of human immunodeficiency virus infection (HIV). Testing for HIV is
not necessary unless clinically indicated
14. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Testing for HBV
or HCV status is not necessary unless clinically indicated or if the patient has a
history of HBV or HCV infection.
15. Patients receiving systemic steroid therapy or any immunosuppressive medication.
Local steroid therapies (eg, otic, ophthalmic, intra-articular or inhaled
medications) are acceptable.
16. History of bleeding diathesis
17. Pregnant, likely to become pregnant, or breastfeeding women
18. Uncontrolled concurrent illness, evaluated at investigator discretion
19. Biliary obstruction, biliary stent or prior biliary surgery except cholecystectomy,
or any anatomic abnormalities that would interfere with immunoembolization or
chemoembolization
20. Patients with occlusion of the main portal vein
21. Inadequate collateral flow around an occluded portal vein as determined by
angiography
22. Arteriovenous shunt identified on arteriography of the hepatic artery
23. Any medical condition that, in the Investigator's judgement, would prevent patient
participation in the clinical study due to safety concerns, compliance with study
procedures or interpretation of study results
Part 1 Only:
a. History of severe immediate or delayed hypersensitivity reaction to GM-CSF
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Thomas Jefferson University
Address:
City:
Philadelphia
Zip:
19107
Country:
United States
Contact:
Last name:
Marlana Orloff, MD
Phone:
215-955-8874
Email:
marlana.orloff@jefferson.edu
Contact backup:
Last name:
Tina Savio
Phone:
215-955-8874
Email:
tina.savio@jefferson.edu
Investigator:
Last name:
Marlana Orloff, MD
Email:
Principal Investigator
Start date:
October 31, 2024
Completion date:
August 15, 2026
Lead sponsor:
Agency:
Thomas Jefferson University
Agency class:
Other
Collaborator:
Agency:
Sidney Kimmel Cancer Center at Thomas Jefferson University
Agency class:
Other
Source:
Thomas Jefferson University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06626516
