Tebentafusp in Molecular Relapsed Disease (MRD) Melanoma

Inclusion Criteria:

A patient will be eligible for inclusion in cohort A or B if all of the following criteria apply:

1. Uveal or cutaneous melanoma with MRD detected in molecular screening, and repeatconfirmation of MRD in the sample taken as part of screening for the main study.

2. Written (signed and dated) informed consent.

3. Male or female, Age 18 years and above.

4. Life expectancy of at least 3 months.

5. ECOG performance score of 0 or 1.

6. No evidence of metastatic disease on a CT scan of neck/thorax/abdomen/pelvis forcohorts A and B and also on MRI liver for uveal melanoma for cohort B.

7. Those receiving prior immunotherapy must have recovered from any immune-mediatedadverse events (≤ grade 1) other than endocrinopathies on stable replacementtherapy.

8. Haematological and biochemical indices within normal ranges (refer to protocol forranges)

Exclusion Criteria:

A patient will not be eligible for tebentafusp administration if any of the following apply:

1. Treatment with any other investigational agent, or participation in anotherinterventional clinical trial within 28 days prior to enrolment.

2. Uveal or cutaneous melanoma patients who present radiologically or clinicallydetectable disease during screening.

3. Active infection requiring systemic antibiotic therapy. Patients requiring systemicantibiotics for infection must have completed therapy before Screening is initiated

4. Other psychological, social or medical condition, physical examination finding or alaboratory abnormality that the Investigator considers would make the patient a poortrial candidate or could interfere with protocol compliance or the interpretation oftrial results.

5. Any other active malignancy, with the exception of malignancies that were treatedcuratively and have not recurred within 2 years after completion of treatment;completely resected basal cell and squamous cell skin cancers; any malignancyconsidered to be indolent and that has never required therapy; and completelyresected carcinoma in situ of any type

6. Patients who are known to be serologically positive for Hepatitis B, Hepatitis C orHIV. This study does not require testing to confirm eligibility unless clinicallyindicated.

7. Clinically significant cardiac disease or impaired cardiac function (New York HeartAssociation grade ≥ 2), including myocardial infarction or unstable angina pectoriswithin 6 months of screening.

8. Active autoimmune disease or a documented history of autoimmune disease within 3years of screening (diabetes mellitus, vitiligo, managed hypothyroidism, psoriasisand managed asthma are not exclusions).

9. Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment.For cytotoxic agents that have major delayed toxicity and any prior immunotherapyapproach, 4 weeks is indicated as washout period

10. Presence of NCI CTCAE ≥ grade 2 toxicity (except alopecia, peripheral neuropathy,and ototoxicity, which are excluded if ≥ NCI CTCAE grade 3) due to prior cancertherapy.

11. Patients currently requiring chronic, systemic corticosteroid therapy at any dosefor longer than 2 weeks. Replacement treatment for pituitary or adrenalinsufficiency is permitted. Local steroid therapies (e.g. otic, ophthalmic,intra-articular, or inhaled medications) are acceptable.

12. Use of any live vaccines against infectious diseases within 4 weeks of initiation ofstudy treatment. Non-live vaccination (e.g. influenza) are permitted anytime duringtreatment.

13. Major surgery as defined by the investigator within 2 weeks of the first dose ofstudy treatment (minimally invasive procedures such as bronchoscopy, insertion of acentral venous access device, and insertion of a feeding tube are not consideredmajor surgery).

14. Pregnant or lactating women, or women of childbearing potential unless effectivemethods of contraception are used.

15. Women of child-bearing potential who are sexually active with a non-sterilized malepartner, defined as all women physiologically capable of becoming pregnant, unlessthey are using highly effective contraception during study treatment, and must agreeto continue using such precautions for 6 months after the final dose ofinvestigational product; cessation of birth control after this point should bediscussed with a responsible physician.

16. Male patients must be surgically sterile or use double barrier contraception methodfrom enrolment through treatment and for 6 months following administration of thelast dose of study drug.