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Tebentafusp

Phase 3

Advanced Melanoma | Small molecule | Oncology |Immunocore Holdings plc|Last Updated: Mar 4, 2026

Target and mechanism

Molecular targetPMEL
Target classBinding Agent
ModalitySmall molecule

Success Probability

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Market & Valuation

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Trial Design

RandomizedCONTROLLEDDMCBiomarker
Total Trials1
Total Enrollment540

FDA Designations

No designations recorded

Clinical trial landscape

Tebentafusp · 5 trials · 6 indications

Phase 3 2Phase 2 3
NCT06246149Adjuvant Tebentafusp in High Risk Ocular MelanomaUveal Melanoma
RECRUITING290 Analytics
NCT05549297Tebentafusp Regimen Versus Investigator's Choice in Previously Treated Advanced Melanoma (TEBE-AM)Advanced Melanoma
RECRUITING540 Analytics
PHASE3RECRUITING
Adjuvant Tebentafusp in High Risk Ocular Melanoma
Uveal MelanomaUnlock trial analytics
PHASE3RECRUITING
Tebentafusp Regimen Versus Investigator's Choice in Previously Treated Advanced Melanoma (TEBE-AM)
Advanced MelanomaUnlock trial analytics

Study Endpoints

Primary Endpoints

Recurrence-Free survival (RFS)
8.1 years from first patient in

RFS is defined as the time between randomization and local recurrence, distant recurrence, or death, whichever occurs first

Overall Survival (OS)
Up to ~4 years

OS is the time from randomization to death due to any cause.

Change in ctDNA response
At Baseline, at Week 10 of each 12-week cycle, Up to 24 months]

ctDNA response (defined as ≥0.3 log reduction) in ctDNA-evaluable patients as measured using Signatera assay.

Progression Free Survival (PFS)
Up to 24 months

Progression-free survival (PFS) will be defined as the elapsed time in months from the first date of study treatment until documented disease progression, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or death from any cause, whichever is earlier. For participants who remain alive without progression, follow-up time will be censored at the date of last disease assessment.

Number of Participants Experiencing Treatment-Related Adverse Events
Up to 24 months

The number of participants experiencing treatment-related adverse events (AEs) and serious adverse events (SAEs) in participants receiving protocol therapy will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5, per physician discretion.

Estimate the rate of molecular response (MR) to tebentafusp in each of 2 cohorts A. Cutaneous melanoma with MRD B. Uveal melanoma with MRD
ctDNA taken at baseline until end of treatment (maximum of 6 months)

Best response to treatment, with partial molecular response (pMR) defined as a decrease in the allele frequency of the index mutation(s), and complete molecular response (cMR) as no detectable mutation(s)

Secondary Endpoints

Overall Survival (OS)
8.1 years from first patient in
Occurrence of Adverse Events
8.1 years from first patient in
Health-related Quality of Life
8.1 years from first patient in
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
TebentafuspEXPERIMENTALParticipants will receive tebentafusp 20 mcg on week 1, 30 mcg on week 2, 68 mcg on week 3, and 68 mcg weekly thereafter for 6 months i.e., maximum 26 infusions.
ObservationNO_INTERVENTION -
Arm A: Tebentafusp MonotherapyEXPERIMENTALParticipants receive tebentafusp as single agent.
Arm B: Tebentafusp + PembrolizumabEXPERIMENTALParticipants receive tebentafusp in combination with pembrolizumab.
Arm C: Investigator's ChoiceEXPERIMENTALParticipants receive investigator's choice of therapy.
Tebentafusp (IMCgp100)EXPERIMENTALDose: 20mcg W1D; 30mcg W2D1; 68mcg W3D1and subsequent doses Frequency: Weekly on D1 of 12-week cycles
Tebentafusp in combination with Radioembolization GroupEXPERIMENTALParticipants in this group will first be administered Yttrium 90 Trans-Arterial Radioembolization (Y90 TARE) therapy, followed by a 14 to 28 day recovery period. Participants will then be administered Tebentafusp once weekly during every 28-day cycle. Participants may receive up to 24 months or 24 cycles of Tebentafusp therapy. Total participation is about 3 years.
Cutaneous melanoma with molecular relapsed diseaseEXPERIMENTALtebentafusp weekly IV escalating in the first treatment cycle with dose 20 mcg on day 1, 30 mcg on day 8, 68 mcg on days 15 and 22. Thereafter weekly doses will be 68 mcg IV for 6 months.
Uveal melanoma with molecular relapsed diseaseEXPERIMENTALtebentafusp weekly IV escalating in the first treatment cycle with dose 20 mcg on day 1, 30 mcg on day 8, 68 mcg on days 15 and 22. Thereafter weekly doses will be 68 mcg IV for 6 months.

Interventions

NameTypeDescription
TebentafuspDRUGTebentafusp will be administered weekly i.v.
Tebentafusp with PembrolizumabDRUGSoluble gp100-specific T cell receptor with anti-CD3 scFV in combination with pembrolizumab
Investigators ChoiceDRUGInvestigators choice of therapy
TheraSphere™ Yttrium-90 Trans-Arterial RadioembolizationRADIATIONParticipants will undergo radiographic and 99mTC-labeled macroaggregated albumin (99mTc-MAA) assessment for suitability prior to Y-90 absorbed glass microsphere treatment per institutional procedures. Y-90 trans-arterial radioembolization (TARE) is a standard of care treatment for intrahepatic metastases of uveal melanoma as indicated in the National Comprehensive Cancer Network (NCCN) consensus guidelines (NCCN Guidelines®, 2023). Y-90 absorbed glass microspheres will be administered at least one time prior to initiating Tebentafusp treatment. After the Y90-TARE procedure, participants will have a 14- to 28-day Y-90 TARE Recovery Period.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites14

Inclusion Criteria: * Primary non-metastatic UM, except iris melanoma, after definitive treatment either by surgery or radiotherapy * Time from primary treatment smaller than 11 weeks (note that the maximum time between primary treatment and randomization is 12 weeks ) * High-risk according to eith...

Countries:BelgiumFranceGermanyNetherlandsPolandSpainSwedenUnited KingdomUnited StatesAustraliaAustriaCanadaItalySwitzerland
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Frequently asked questions about Tebentafusp

What is Tebentafusp used for?

Tebentafusp is an investigational oncology therapy being studied for metastatic uveal melanoma, advanced melanoma, melanoma of the skin, and uveal melanoma. It is in clinical development for these indications and is not yet approved by regulatory authorities.

What does Tebentafusp target?

Tebentafusp targets PMEL, a protein involved in melanocyte biology. It is designed as a binding agent against this target, which is relevant to its mechanism of action in melanoma. The drug is being evaluated in patients with specific HLA-A*0201 status in some trials.

Who is developing Tebentafusp?

Tebentafusp is being developed by Immunocore Holdings plc, a biopharmaceutical company. The company is publicly traded under the ticker symbol IMCR. Immunocore is conducting clinical trials to evaluate the drug's safety and efficacy in melanoma.

What phase is Tebentafusp in?

Tebentafusp is in Phase 3 clinical development. It is also being studied in Phase 2 trials. The drug remains investigational and has not completed the clinical development process required for regulatory approval.

What clinical trials is Tebentafusp in?

Tebentafusp is being evaluated in several clinical trials, including NCT05315258 for molecular relapsed disease melanoma, NCT05549297 for previously treated advanced melanoma, NCT06070012 for previously untreated metastatic uveal melanoma, and NCT06246149 for adjuvant treatment of high risk ocular melanoma.

Is Tebentafusp the same as other names?

Tebentafusp is the primary name used for this drug in clinical trials and development. No alternative names have been reported for this investigational therapy in the available clinical trial information.