A Randomised Phase II Study of Roginolisib in Patients With Advanced/Metastatic Uveal Melanoma

Inclusion Criteria:

1. Male or female aged 18 years or older;

2. Histologically or cytologically proven diagnosis of advanced or metastatic UM orocular melanoma (arising from ocular melanocytes regardless of intraocular location)

3. Patients who have progressed following at least 1 prior immunotherapy treatment foradvanced or metastatic UM. For patients who are HLA-A*02:01 positive prior treatmentshould have included tebentafusp, if available or patients clinically suitable.Patients who have also received prior melphalan hepatic infusion may be included;

4. Presence of at least one lesion suitable for biopsy. Biopsies will be mandatory atScreening and C5D1 (see Sections 8.1.3 and 8.6 for more information);

5. Presence of at least one measurable lesion as per RECIST v1.1. Any lesion that isbiopsied cannot be used as a measurable lesion for the purposes of RECIST v1.1assessments;

6. ECOG performance status of 0 to 1;

7. Male or female patients of child-bearing potential must be willing to use highlyeffective forms of contraception (refer to APPENDIX 7 for details on highlyeffective methods of contraception and definitions of women of childbearingpotential and of fertile men)

8. All other relevant medical conditions must be well managed and stable, in theInvestigator's opinion, for at least 28 days prior to first dose of roginolisib;

9. Provision of signed and dated, written informed consent prior to any study specificprocedures, sampling and analyses.

Exclusion Criteria:

1. Inability to swallow oral medication;

2. a). History of a prior Grade 3 or 4 irAE or any grade ocular irAE from priorimmunotherapy which did not respond to corticosteroid therapy or resolved withtreatment interruptions and returned to at least Grade 1; b). Have not recoveredfrom toxic effect(s) of prior therapy to ≤ Grade 1, other than alopecia or fatigueor neuropathy which must be ≤ Grade 1;

3. Presence of symptomatic or untreated CNS metastases or CNS metastases that requiredoses of corticosteroids within the prior 3 weeks to first dose of roginolisib.Patients with brain metastases are eligible if lesions have been treated withlocalised therapy and there is no evidence of progressive disease for at least 4weeks prior to the first dose of IMP;

4. Abnormal liver enzymes defined as:

5. ALT or AST ≥ 3× upper limit of normal (ULN) (≥ 5× ULN in patients with livermetastases);

6. Total bilirubin ≥ 1.5 × ULN are excluded unless direct bilirubin is ≤ ULN. Ifthere is no institutional ULN, then direct bilirubin must be < 40% of totalbilirubin to be eligible (except patients with Gilbert syndrome);

7. Any other clinically significant out of range laboratory values;

8. Clinically significant cardiac disease or impaired cardiac function which may limitthe patient´s participation in the clinical study. These may include unstable angina (i.e., not responsive to medical intervention), myocardial infarct in last 6 months,QTcF prolongation of more than 500 ms;

9. Evidence of interstitial lung disease or active, non-infectious pneumonitis,pulmonary fibrosis;

10. Active infection requiring systemic antibiotic therapy. Patients requiring systemicantibiotics for infection must have completed therapy at least 1 week prior to thefirst dose of IMP;

11. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection perinstitutional protocol;

12. Malignant disease, other than that being treated in this study (e.g., skin/cutaneousand/or mucosal melanoma). Exceptions to this exclusion include the following:malignancies that were treated curatively and have not recurred within 2 years priorto first dose of IMP; completely resected basal cell and squamous cell skin cancers;any malignancy considered to be indolent and that has never required therapy; andcompletely resected carcinoma in situ of any type;

13. Any medical condition that would, in the Investigator's or Sponsor'sjudgment, prevent the patient's participation in the clinical study due tosafety concerns, compliance with clinical study procedures or interpretation ofstudy results;

14. Treatment with anti-tumour medications or investigational drugs within 14 days or 5half-lives (whichever is longer) of administration of first dose of IMP;

15. Major surgery within 2 weeks of the first dose of IMP (minimally invasive proceduressuch as bronchoscopy, tumour biopsy, insertion of a central venous access device,and insertion of a feeding tube are not considered major surgery and are notexclusionary);

16. Radiotherapy within 4 weeks of the first dose of IMP, with the exception ofpalliative radiotherapy to a limited field, such as for the treatment of bone painor a focally painful tumour mass;

17. Pregnant, likely to become pregnant, or lactating women.