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Tebentafusp-tebn With LDT in Metastatic UM

ConditionMetastatic Uveal Melanoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorThomas Jefferson University

About this trial

This study is 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, the Prinicipal Investigator 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, the study will investigate the efficacy of tebentafusp-tebn in combination with TACE in patients with bulky hepatic disease.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Prior surgery or ablation for oligometastatic disease is allowable.

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.

Platelet count ≥ 100,000/mm³

Hemoglobin > 8.0g/dL

Disqualifiers

Failure to meet any of the criteria set forth in the Inclusion criteria section

History of prior tebentafusp-tebn use

Prior chemoembolization in Part 2 is not permitted

History of severe immediate or delayed hypersensitivity reaction to biologic drugs, monoclonal antibodies, iodinated contrast agent

Trial design

Design model

Sequential

Treatments tested in this trial

  • Tebentafusp-Tebn

    Drug

    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.

  • GM-CSF (Sargramostim)

    Drug

    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.

  • BCNU

    Drug

    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

Treatment groups

109 Participants
are divided into 4 treatment groups
Group A: Part 1A: Safety Lead-inExperimental treatment 2 interventions
Group B: Part 1B: CombinationActive comparator 2 interventions
Group C: Part 1B: Tebentafusp-tebn aloneActive comparator 1 intervention
Group D: Part 2: Efficacy of ComboActive comparator 2 interventions

Trial outcomes

Primary outcomes

1

Part 1A: Safety lead-in

Adverse events (AEs) according to NCI CTCAE Version 5.0. Safety and tolerability data will be presented by treatment arm using the safety population. Safety data will be summarized descriptively and will not be formally analyzed. AE presentation will include incidence, severity, and relationship to study drug.

Time frame
From when the patient receives the first study treatment to 7 days (for non-serious AEs) or 30 days (for SAEs) after completion of study treatment or withdrawal from the study.
2

Part 1A: Efficacy

6-month progression-free survival rate as determined by response criteria (RECIST 1.1). Will be summarized by count and percentage along with the two-sided 90% exact confidence interval (CI).

Time frame
From when the patient receives the first study treatment to 6 months after first treatment
3

Part 1B: Progression-free Survival

Defined as the time from the date of randomization until the date of objective disease progression or death by any cause. The primary Progression-free Survival (PSF) analysis will use a one-sided log-rank test, with a type I error of 0.05. In addition, PFS will be analyzed using Cox proportional hazards model and the estimated HR with 90% Confidence Interval (CI) will be reported. Kaplan-Meier curves of PFS will be presented by treatment arm along with estimated medians PFS (CIs).

Time frame
From when patient joins study until disease progression or death, up to 2.5 years after last patient's last treatment.
4

Part 2: 6-month progression-free survival rate

As determined by response criteria (RECIST 1.1). Defined as the proportion of patients alive and progression-free at 6 months after treatment initiation. Will be summarized by count and percentage. In addition, a two-sided 90% Confidence Interval (CI) based on the method of Koyama and Chen will be provided. This method is appropriate because it is proposed for Simon's 2-stage design, accounting for the inherent futility analysis.

Time frame
From when the patient receives the first study treatment to 6 months after first treatment.

Secondary outcomes

1

All toxicities using the NCI CTCAE Version 5.0

Safety and tolerability data will be presented by treatment arm using the safety population. Safety data will be summarized descriptively and will not be formally analyzed. AE presentation will include incidence, severity, and relationship to study drug.

Time frame
From when the patient receives the first study treatment to 7 days (for non-serious AEs) or 30 days (for SAEs) after completion of study treatment or withdrawal from the study.
2

Overall response rate (ORR)

Count and percentage of patients with a tumor response (Complete Response/Partial Response)

Time frame
From when the patient receives the first study treatment to at least one year (and up to 2.5 years) after discontinuing treatment
3

Liver-specific progression-free survival

As determined by response criteria (RECIST 1.1). Defined as the proportion of patients alive and progression-free at 6 months after treatment initiation. Will be summarized by count and percentage.

Time frame
From when patient joins study until disease progression or death, up to 2.5 years after last patient's last treatment.
4

Overall survival

Measured from the start of the treatment to death due to any cause. Date and cause of death will be recorded. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive. The cause of death will be categorized as either cancer-related or cancer-unrelated.

Time frame
From the start of the treatment to death due to any cause (assessed up to 2.5 years after last patient's last treatment)

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Thomas Jefferson University

Lead sponsor

Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

Collaborator

Wills Eye

Collaborator

Source ClinicalTrials.gov
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