Are you interested in being a Principal Investigator

If you are interested in being a Principal Investigator or opening as recruiting TebeMRD site, please contact us via email at octo-tebemrd@oncology.ox.ac.uk.

Full Title of study:A Phase II non-randomized, Open-label, Multi-centre Study of the Safety and Efficacy of Tebentafusp in Melanoma with Molecular Relapsed Disease
Short Title:Tebentafusp in MRD Melanoma
Trial Acronym:TebeMRD
Clinical Phase:Phase 2
Study Design:

This is an unblinded non-randomised, open label, safety and efficacy study involving 2 patient cohorts:

•              A: Cutaneous melanoma with molecular relapsed disease (MRD)

•              B: Uveal melanoma with MRD

Patients will receive up to six months of tebentafusp, administered weekly IV, and then followed for molecular and clinical relapse.

Number of centres:

Pre-screening and molecular screening phase – up to 50 sites

Main treatment study – up to 10 sites

 ObjectivesEndpoints
Primary Endpoint:

Estimate the rate of molecular response (MR) to tebentafusp in each of the 2 cohorts:

 

  1. Cutaneous melanoma with MRD
  2. Uveal melanoma with MRD

 

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:

 

Evaluate the efficacy of tebentafusp in each cohortRelapse free survival at 12 months; duration of MR; overall survival
Assess the safety and tolerability of tebentafusp in MRD

Incidence and severity of adverse events according to NCIC CTCAE v5.0/2019 Lee et al criteria; dose reductions, interruptions and cessations in the course of treatment

Assess the rate of molecular relapse in;

  1. Cutaneous melanoma
  2. Uveal melanoma

Percentage of patients with molecular relapse at baseline, within 6 months and over 12 months of monitoring.

Tertiary Endpoints:

 

Characterise pharmacodynamic changes with tebentafusp treatmentChanges in peripheral T cell populations and in serum cytokines and other analytes
Preliminary evaluation of response rate in gp100 expressing melanomaBest molecular response in cohorts A and B
Planned enrolment:Approximately 850 patients will be enrolled from 50 centres to screen for HLA *0201 status and then followed for MRD. Up to 50 patients identified with MRD will be invited to be treated with tebentafusp at up to 10 treating centres in the UK. 
Target Population:The patient population will be drawn from those completing adjuvant or local therapy for intermediate or high risk melanoma. Potential participants will be approached as they enter the last 3 months of adjuvant treatment for resected cutaneous melanoma, or within 9 months of completing such treatment. In the case of uveal melanoma entry will be open to those within 3 years of completing treatment for their primary tumour or oligometastatic disease.
Investigational Medicinal Product(s)Tebentafusp supplied as concentrate for solution for infusion and diluted prior to administration. 0.2 mg/mL drug product will be provided as a sterile, refrigerated solution in glass vials.  Tebentafusp will be administered IV at weekly intervals. The dose will escalate in the first treatment cycle being 20mcg on day 1, 30mcg on d8, 68mcg on d15 and 68mcg on d22. Thereafter weekly doses will be 68mcg IV, notwithstanding modifications for toxicity.
Other interventions:Participants in molecular screening will have blood drawn for central testing for MRD every 3 months for up to 24 months.
Treatment DurationPatients will receive tebentafusp for up to 6 months.
Follow-up duration

The study will continue until all patients treated with tebentafusp in cohorts A and B have been followed for up to 12 months after completing treatment. Patients will be seen every 3 months (+/- 10 days) after completing tebentafusp treatment. At each visit they will have a blood draw for molecular analysis until they are determined to have disease progression, they withdraw consent or their participation in the study ends. After disease progression they will be followed for survival only until the end of the study (12 months post IMP administration of the last participant).

End of studyLast Patient Last Visit