Phase II Open-label, Multi-center Study of Tebentafusp in HLA-A*0201 Positive Previously Untreated Metastatic Uveal Melanoma (mUM) With Integrated Circulating Tumor DNA (ctDNA) Biomarker (TARGET-tebe)
This is a phase II open-label, single-arm, multi-center study of tebentafusp in HLA- A\*0201 positive previously untreated (1L) untreated metastatic uveal melanoma (mUM) with an integrated circulating tumor DNA (ctDNA) biomarker.
⁃ Histologically or cytologically confirmed untreated metastatic uveal melanoma (mUM).
⁃ HLA-A\*0201 genotype positive as assessed using a CLIA-certified blood typing method and confirmed by central review.
• If HLA-A status is not known, blood for HLA-A testing must be submitted during Screening, and HLA-A\*0201 positive status confirmed prior to enrollment using a CLIA- certified blood typing method.
• If the patient is known to be HLA-A\*0201 positive, this information must be provided in the Screening packet and centrally reviewed by treating PI and Sponsor-Investigator prior to enrollment.
• The following HLA testing methodologies are suitable to determine HLA-A\*0201 positivity:
‣ Multiplex real-time PCR based testing performed by entities including but not limited to Labcorp, and American Red Cross.
⁃ HLA testing as part of peripheral blood molecular profiling technology including but not limited to Caris Life Sciences Molecular Profiling Technology.
• Patients be willing to undergo ctDNA assessment using Signatera assay.
• Have provided newly obtained core biopsy of a tumor lesion not previously irradiated.
• Adequate organ function on screening labs obtained within 4 weeks of Week 1 day 1
• Must meet the following criteria related to prior treatment:
‣ No prior systemic therapy in the metastatic or advanced setting including chemotherapy, or targeted therapy.
• NOTE: Patients must be tebentafusp naïve.
∙ NOTE: Patients must not have received prior PD-1, CTLA-4, LAG-3 directed Immune Checkpoint Inhibitor therapy delivered in the adjuvant, and/or neoadjuvant settings unless such therapy was received \>6 months prior initial diagnosis of mUM.
⁃ No prior regional, liver-directed therapy including chemotherapy, radiotherapy, or embolization.
⁃ Prior surgical resection of oligometastatic disease is allowed.
⁃ Prior neoadjuvant or adjuvant therapy is allowed provided administered in the curative setting in patients with localized disease.
• Life expectancy of \>6 months as estimated by the investigator.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 at Screening.
• Patients have measurable disease according to RECIST v.1.1.
• All other relevant medical conditions must be well-managed and stable, in the opinion of the investigator, for at least 28 days prior to first administration of study drug.