A Randomised Phase II Study of Roginolisib in Patients With Advanced/Metastatic Uveal Melanoma (OCULE-01)

A Phase II, Multi-centre, Open Label, Randomised Study to Evaluate the Anti-tumour Activity of Roginolisib in Patients With Advanced/Metastatic Ocular/Uveal Melanoma

The goal of this clinical trial is to learn how roginolisib works in comparison to standard treatment in adult patients with uveal/ocular melanoma. The main questions it aims to answer are:

Does roginolisib extend overall survival compared to standard treatment? How does dosing of roginolisib impact quality of life compared to standard treatment?

Study Overview

• Status: Active, not recruiting
• Conditions: Ocular Melanoma; Uveal Melanoma
• Intervention / Treatment: Drug: roginolisib; Drug: Investigator choice of standard therapy

Detailed Description

A Phase II open-label, randomised, parallel-arm study, which will assess the clinical efficacy of oral roginolisib (IOA 244 [roginolisib hemi-fumarate]) as monotherapy against a control of Investigator´s treatment choice in patients with advanced or metastatic uveal melanoma (UM).

This study will enrol approximately 85 male and female patients aged over 18 years with advanced or metastatic UM, who have progressed following at least 1 prior immunotherapy treatment. The disease must be measurable (i.e., at least 1 measurable lesion) as per RECIST v1.1 by Computerised Tomography (CT) scan or Magnetic Resonance Imaging (MRI).

• Study Type: Interventional
• Enrollment (Estimated): 85
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Bari, Italy, 70124
    • SSD Tumori Rari e Melanoma Viale Orazio Flacco
  • Napoli, Italy, 80131
    • IRCSS National Cancer Institute, "G.Pascale" Foundation Dip. CORP-S di Ricerca ed Assistenziale Cute, Melanoma lmmunologia Oncologica Sperimentale e Terapie Innovative
  • Padua, Italy, 35128
    • IRCSS Istituto Oncologico Veneto UOS Oncologia 2 del Melanoma Ospedale Busonera
  • Rozzano, Italy, 20089
    • IRCCS Istituto Clinico Humanitas
  • Siena, Italy, 53100
    • A.O.U.S. Santa Maria delle Scotte
• Spain
  • Barcelona, Spain, 08908
    • Institut Catala d'Oncologia - ICO L'Hospitalet
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Santiago de Compostela, Spain, 15706
    • Complejo Hospitalario Universitario de Santiago - CHUS
  • Seville, Spain
    • Hospital Universitario Virgen Macarena, University of Seville
  • Valencia, Spain, 46014
    • Consorcio Hospital General Universitario de València - CHGUV
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre, Glasgow (NHS Greater Glasgow & Clyde)
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital
  • London, United Kingdom, NW1 2PG
    • University College London Hospital NHS
  • Southampton, United Kingdom, SO16 6YD
    • University Hospital Southampton NHS Foundation
  • Middlesex
    • Northwood, Middlesex, United Kingdom, HA6 2RN
      • East and North Hertfordshire NHS Trust (Mount Vernon Cancer Centre)
  • Wirral
    • Bebington, Wirral, United Kingdom, CH63 4JH
      • The Clatterbridge Cancer Centre NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female aged 18 years or older;
2. Histologically or cytologically proven diagnosis of advanced or metastatic UM or ocular melanoma (arising from ocular melanocytes regardless of intraocular location)
3. Patients who have progressed following at least 1 prior immunotherapy treatment for advanced or metastatic UM. For patients who are HLA-A*02:01 positive prior treatment should 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 at Screening 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 is biopsied cannot be used as a measurable lesion for the purposes of RECIST v1.1 assessments;
6. ECOG performance status of 0 to 1;
7. Male or female patients of child-bearing potential must be willing to use highly effective forms of contraception (refer to APPENDIX 7 for details on highly effective methods of contraception and definitions of women of childbearing potential and of fertile men)
8. All other relevant medical conditions must be well managed and stable, in the Investigator'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 specific procedures, 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 prior immunotherapy which did not respond to corticosteroid therapy or resolved with treatment interruptions and returned to at least Grade 1; b). Have not recovered from toxic effect(s) of prior therapy to ≤ Grade 1, other than alopecia or fatigue or neuropathy which must be ≤ Grade 1;
3. Presence of symptomatic or untreated CNS metastases or CNS metastases that require doses of corticosteroids within the prior 3 weeks to first dose of roginolisib. Patients with brain metastases are eligible if lesions have been treated with localised therapy and there is no evidence of progressive disease for at least 4 weeks prior to the first dose of IMP;

4. Abnormal liver enzymes defined as:

   1. ALT or AST ≥ 3× upper limit of normal (ULN) (≥ 5× ULN in patients with liver metastases);
   2. Total bilirubin ≥ 1.5 × ULN are excluded unless direct bilirubin is ≤ ULN. If there is no institutional ULN, then direct bilirubin must be < 40% of total bilirubin to be eligible (except patients with Gilbert syndrome);
5. Any other clinically significant out of range laboratory values;
6. Clinically significant cardiac disease or impaired cardiac function which may limit the 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;
7. Evidence of interstitial lung disease or active, non-infectious pneumonitis, pulmonary fibrosis;
8. Active infection requiring systemic antibiotic therapy. Patients requiring systemic antibiotics for infection must have completed therapy at least 1 week prior to the first dose of IMP;
9. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional protocol;
10. Malignant disease, other than that being treated in this study (e.g., skin/cutaneous and/or mucosal melanoma). Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to 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; and completely resected carcinoma in situ of any type;
11. Any medical condition that would, in the Investigator's or Sponsor's judgment, prevent the patient's participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results;
12. Treatment with anti-tumour medications or investigational drugs within 14 days or 5 half-lives (whichever is longer) of administration of first dose of IMP;
13. Major surgery within 2 weeks of the first dose of IMP (minimally invasive procedures such as bronchoscopy, tumour biopsy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery and are not exclusionary);
14. Radiotherapy within 4 weeks of the first dose of IMP, with the exception of palliative radiotherapy to a limited field, such as for the treatment of bone pain or a focally painful tumour mass;
15. Pregnant, likely to become pregnant, or lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 - Roginolisib 80mg; IOA-244: 80 mg (corresponding to 72 mg roginolisib) daily	Drug: roginolisib; rognolisib; Other Names: IOA-244
Active Comparator: Arm 2 - Investigator choice of standard of care; Investigator´s choice of therapy	Drug: Investigator choice of standard therapy; Investigator will choose the most appropriate treatment standardly given to patients
Experimental: Arm 3 - Roginolisib 40mg; IOA-244: 40 mg (corresponding to 36 mg roginolisib) daily	Drug: roginolisib; rognolisib; Other Names: IOA-244

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	To evaluate clinical efficacy of roginolisib as single agent, against Investigator's choice of therapy by assessment of overall survival (OS)	Patients will be followed up for overall survival every 12 weeks, for 96 weeks from last patient enrolled, until their death or end of the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to response	Time to Response is defined as the time from date of first dose of IMP until the date of first documented objective response	Every 8 weeks whilst on treatment anticipated to be 52 weeks
Safety and tolerability	Assessed by AEs, laboratory parameters, vital signs, physical exam, ECG and ECOG status	Every 4 weeks whilst on treatment anticipated to be 52 weeks
Safety of 40 vs 80 mg of roginolisib	Assessed by AEs, laboratory parameters, vital signs, physical exam, ECG and ECOG status	Every 4 weeks whilst on treatment anticipated to be 52 weeks
Health care utilisation	Assessed by health resource used	Every 4 weeks whilst on treatment anticipated to be 52 weeks
Progression free survival (PFS)	PFS measured from the time from the date of the first dose of IMP until the earliest date of disease progression as determined by radiographic/objective disease assessment as per RECIST v1.1	Patients will be followed up for progression free survival every 8 weeks, for 96 weeks from last patient enrolled, until progression of disease, their death or end of the study
Objective response rate (ORR)	ORR defined as percentage of patients with a Complete Response (CR) or Partial Response (PR)	Every 8 weeks whilst on treatment anticipated to be 52 weeks
Duration of response (DOR)	DOR defined as the time from the date of first documented response (CR, PR) by RECIST v1.1 until the date of documented progression or death in the absence of disease progression	Every 8 weeks up to 96 weeks from start of treatment
Disease control rate (DCR)	DCR is defined as the proportion of patients with a Best Objective Response (BOR) of CR or PR or Stable disease (SD) recorded at ≥8 weeks (±1 week),	Every 8 weeks whilst on treatment anticipated to be 52 weeks
Clinical benefit rate (CBR)	CBR is defined as the proportion of patients with a BOR of CR or PR or SD recorded at Cycle 5 Day 1	Measured at Cycle 5 - approximately 16 weeks from start of dosing
Pharmacokinetics (PK)	Concentration of roginolisib at pre-dose and steady state levels (including Area under the curve [AUC], population PK)	Every 4 weeks for 52 weeks from start of treatment
Quality of Life	Changes in Patient Reported Outcomes (PRO) relative to baseline. Patients to complete EuroQoL Research Foundation EQ-5D-5L Health questionnaire	Every 4 weeks for 52 weeks from start of treatment
Quality of Life	Changes in Patient Reported Outcomes (PRO) relative to baseline. Patients to complete European Organisation for Research and Treatment of Cancer (EORTC QlQ-C30)	Every 4 weeks for 52 weeks from start of treatment
Quality of Life	Changes in Patient Reported Outcomes (PRO) relative to baseline. Patients to complete Epworth Sleepiness Scale (ESS) questionnaire	Every 4 weeks for 52 weeks from start of treatment
Quality of Life	Changes in Patient Reported Outcomes (PRO) relative to baseline. Patients to complete Fatigue Severity Scale (FSS)	Every 4 weeks for 52 weeks from start of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circulating Tumour Deoxyribonucleic Acid (ctDNA)	To assess any treatment-related changes in the pre and on treatment levels of circulating DNA from blood	Every 4 weeks for 52 weeks from start of treatment

Collaborators and Investigators

• Sponsor: iOnctura
• Investigators: Study Director: Michael Lahn, MD, iOnctura

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: November 18, 2024
• First Submitted That Met QC Criteria: November 29, 2024
• First Posted (Actual): December 4, 2024

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Melanoma; Uveal; Ocular
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Eye Diseases; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Eye Neoplasms; Uveal Diseases; Skin and Connective Tissue Diseases; Uveal Neoplasms; Melanoma; Uveal Melanoma
• Other Study ID Numbers: IOA-244-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No