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

NCT06717126 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: IOA-244-201
• Study Type: interventional
• Target: 85
• Locations: 3 countries
• Sites: 16

Brief Summary

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?

Conditions

Uveal Melanoma; Ocular Melanoma

Keywords

Uveal; Ocular; Melanoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• Progression free survival (PFS)

  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)

  Every 8 weeks whilst on treatment anticipated to be 52 weeks

• Duration of response (DOR)

  Every 8 weeks up to 96 weeks from start of treatment

• Time to response

  Every 8 weeks whilst on treatment anticipated to be 52 weeks

• Disease control rate (DCR)

  Every 8 weeks whilst on treatment anticipated to be 52 weeks

Other Outcomes (1)

• Circulating Tumour Deoxyribonucleic Acid (ctDNA)

  Every 4 weeks for 52 weeks from start of treatment

Study Arms (3)

Arm 1 - Roginolisib 80mg

EXPERIMENTAL

IOA-244: 80 mg (corresponding to 72 mg roginolisib) daily

Drug: roginolisib

Arm 2 - Investigator choice of standard of care

ACTIVE COMPARATOR

Investigator´s choice of therapy

Drug: Investigator choice of standard therapy

Arm 3 - Roginolisib 40mg

EXPERIMENTAL

IOA-244: 40 mg (corresponding to 36 mg roginolisib) daily

Drug: roginolisib

Interventions

roginolisib DRUG

rognolisib

Also known as: IOA-244

Arm 1 - Roginolisib 80mg; Arm 3 - Roginolisib 40mg

Investigator choice of standard therapy DRUG

Investigator will choose the most appropriate treatment standardly given to patients

Arm 2 - Investigator choice of standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 18 years or older;
• Histologically or cytologically proven diagnosis of advanced or metastatic UM or ocular melanoma (arising from ocular melanocytes regardless of intraocular location)
• 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;
• 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);
• 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;
• ECOG performance status of 0 to 1;
• 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)
• 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;
• Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses.

You may not qualify if:

• Inability to swallow oral medication;
• 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;
• 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;
• Abnormal liver enzymes defined as:
• ALT or AST ≥ 3× upper limit of normal (ULN) (≥ 5× ULN in patients with liver metastases);
• 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);
• Any other clinically significant out of range laboratory values;
• 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;
• Evidence of interstitial lung disease or active, non-infectious pneumonitis, pulmonary fibrosis;
• 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;
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional protocol;
• 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;
• 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;
• 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;
• Pregnant, likely to become pregnant, or lactating women.

Sponsors & Collaborators

• iOnctura: lead

Study Sites (16)

SSD Tumori Rari e Melanoma Viale Orazio Flacco

Bari, 70124, Italy

Location

IRCSS National Cancer Institute, "G.Pascale" Foundation Dip. CORP-S di Ricerca ed Assistenziale Cute, Melanoma lmmunologia Oncologica Sperimentale e Terapie Innovative

Naples, 80131, Italy

Location

IRCSS Istituto Oncologico Veneto UOS Oncologia 2 del Melanoma Ospedale Busonera

Padua, 35128, Italy

Location

IRCCS Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

A.O.U.S. Santa Maria delle Scotte

Siena, 53100, Italy

Location

Institut Catala d'Oncologia - ICO L'Hospitalet

Barcelona, 08908, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Complejo Hospitalario Universitario de Santiago - CHUS

Santiago de Compostela, 15706, Spain

Location

Hospital Universitario Virgen Macarena, University of Seville

Seville, Spain

Location

Consorcio Hospital General Universitario de València - CHGUV

Valencia, 46014, Spain

Location

East and North Hertfordshire NHS Trust (Mount Vernon Cancer Centre)

Northwood, Middlesex, HA6 2RN, United Kingdom

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, Wirral, CH63 4JH, United Kingdom

Location

Beatson West of Scotland Cancer Centre, Glasgow (NHS Greater Glasgow & Clyde)

Glasgow, G12 0YN, United Kingdom

Location

University College London Hospital NHS

London, NW1 2PG, United Kingdom

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

University Hospital Southampton NHS Foundation

Southampton, SO16 6YD, United Kingdom

Location

MeSH Terms

Conditions

Uveal Melanoma; Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Michael Lahn, MD

  iOnctura

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomised parallel-arm, open-label

Study Record Dates

• First Submitted: November 18, 2024
• First Posted: December 4, 2024
• Study Start: February 27, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: January 16, 2026

Record last verified: 2026-01

Locations

GB (6); ES (5); IT (5)