ROGINOLISIB for Uveal melanoma | Ocular melanoma (advanced/metastatic)

Inclusion criteria

• {"criterion_text":"- Male or female aged 18 years or older"}
• {"criterion_text":"- Histologically or cytologically proven diagnosis of advanced or metastatic UM or ocular melanoma (arising from ocular melanocytes regardless of intraocular location);"}
• {"criterion_text":"- 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;"}
• {"criterion_text":"- Presence of at least one lesion suitable for biopsy. Biopsies will be mandatory at Screening and C5D1"}
• {"criterion_text":"- 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;"}
• {"criterion_text":"- ECOG performance status of 0 to 1"}
• {"criterion_text":"- 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): a) Women of childbearing potential (WOCBP) must have a negative serum test as per local guidelines during screening and EOT and agree to have regular urine pregnancy testing throughout the study. WOCBP must agree to use highly effective method of contraception throughout the study and until 1 month after last dose of IMP; b) Male patients must agree to use barrier method of contraception [condom plus spermicide] from screening through Safety Follow-up visit, at least 1 month after the last dose of IMP. Men should refrain from donating sperm from the day of first dose of IMP, throughout the study and until 3 months after last dose of IMP. Men with partners of child-bearing potential must also be willing to ensure that their partner uses a highly effective method of contraception for the same duration. Men with pregnant or lactating partners should be advised to use barrier method contraception (e.g., condom plus spermicidal gel) to prevent exposure to the foetus or neonate;"}
• {"criterion_text":"- 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;"}
• {"criterion_text":"- Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses."}

Exclusion criteria

• {"criterion_text":"- Inability to swallow oral medication;"}
• {"criterion_text":"- 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;"}
• {"criterion_text":"- 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;"}
• {"criterion_text":"- 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;, with the exception of prior anticancer agents with long half-lives (e.g., PD-1/PD-L1 targeting agents), which are required to have a washout of 4 weeks prior to the first dose of IMP;"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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;"}
• {"criterion_text":"- Pregnant, likely to become pregnant, or lactating women"}
• {"criterion_text":"- 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;"}
• {"criterion_text":"- 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;"}
• {"criterion_text":"- Abnormal liver enzymes defined as: a) ALT or AST ≥ 3× upper limit of normal (ULN) (≥ 5× ULN in patients with liver metastases); b) 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);"}
• {"criterion_text":"- Any other clinically significant out of range laboratory values;"}
• {"criterion_text":"- 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;"}
• {"criterion_text":"- Evidence of interstitial lung disease or active, non-infectious pneumonitis, pulmonary fibrosis;"}
• {"criterion_text":"- 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;"}
• {"criterion_text":"- Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional protocol;"}

Primary endpoints

• {"endpoint_text":"- OS is defined as the time from randomisation until death from any cause.","definition_or_measurement_approach":"OS is measured as time from randomisation until death from any cause."}

Secondary endpoints

• {"endpoint_text":"- PFS is defined as 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 provided by the Investigators, or death from any cause; ","definition_or_measurement_approach":"Measured from first dose of IMP to radiographic/objective progression per RECIST v1.1 or death."}
• {"endpoint_text":"- ORR is defined percentage of patients with a Complete Response (CR) or Partial Response (PR) determined by Investigator based on appropriate radiographic imaging and consistent with RECIST v1.1","definition_or_measurement_approach":"Proportion of patients achieving CR or PR per Investigator assessment consistent with RECIST v1.1."}
• {"endpoint_text":"- DOR is 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;","definition_or_measurement_approach":"Measured from first documented CR/PR per RECIST v1.1 until documented progression or death."}
• {"endpoint_text":"- Time to Response is defined as the time from date of first dose of IMP until the date of first documented objective response, per RECIST v1.1 as assessed by Investigator;","definition_or_measurement_approach":"Time from first dose to first documented objective response per RECIST v1.1."}
• {"endpoint_text":"- DCR defined as the proportion of patients with a Best Objective Response (BOR) of CR or PR or SD recorded at ≥8 weeks (±1 week), prior to any progressive disease event;","definition_or_measurement_approach":"Proportion of patients with BOR of CR, PR or SD at ≥8 weeks (±1 week) before progression."}
• {"endpoint_text":"- CBR is defined as the proportion of patients with a BOR of CR or PR or SD recorded at C5D1;","definition_or_measurement_approach":"Proportion of patients with BOR of CR, PR or SD recorded at Cycle 5 Day 1."}
• {"endpoint_text":"- Survival probability defined as the probability that an individual survives from date of first dose of IMP until 6 months, 9 months, 12 months and 24 months after end of treatment. Median survival time will also be estimated.","definition_or_measurement_approach":"Kaplan-Meier estimates at specified timepoints (6, 9, 12, 24 months) and median survival estimation."}
• {"endpoint_text":"- Safety and tolerability will be assessed by: • Evaluation of AEs during treatment and followup using National Cancer Institute (NCI) CTCAE v5.0; • Laboratory parameters; • Vital signs, physical examination, 12-lead electrocardiogram (ECG), Eastern Cooperative Oncology Group (ECOG) performance status;","definition_or_measurement_approach":"Adverse events graded per NCI CTCAE v5.0; clinical labs, vitals, physical exam, 12-lead ECG, ECOG PS assessments."}
• {"endpoint_text":"- Concentration of roginolisib at pre-dose and steady state levels (including AUC, population PK);","definition_or_measurement_approach":"Pharmacokinetic sampling to determine pre-dose and steady-state concentrations, AUC and population PK analyses."}
• {"endpoint_text":"- Changes in PRO relative to baseline using following questionnaires: • EQ-5D-5L; • European Organisation for Research Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30; • Epworth Sleepiness Scale (ESS); • Fatigue Severity Scale (FSS).","definition_or_measurement_approach":"Patient-reported outcome measures using listed validated questionnaires compared to baseline."}
• {"endpoint_text":"- Safety and tolerability will be assessed by: • Evaluation of AEs during treatment and followup using NCI CTCAE v5.0; • Laboratory parameters; • Vital signs, physical examination, 12-lead ECG, ECOG performance status.","definition_or_measurement_approach":"Same as other safety endpoint: AEs per NCI CTCAE v5.0 and routine clinical assessments."}
• {"endpoint_text":"- Assessed by health resource use (e.g., hospitalisations, outpatient visits, emergency visits, preparation and time for IMP administration, etc)","definition_or_measurement_approach":"Health care resource use captured (hospitalisations, outpatient visits, emergency visits, IMP administration time) and analysed."}

Spain

Earliest CTIS Part Ii Submission Date

03-09-2024

Latest Decision Or Authorization Date

18-04-2025

Processing Time Days

227

Number Of Sites

5

Number Of Participants

21

Italy

Earliest CTIS Part Ii Submission Date

11-11-2024

Latest Decision Or Authorization Date

19-06-2025

Processing Time Days

220

Number Of Sites

6

Number Of Participants

22

Primary sponsor

Full Name

iOnctura SA

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Propharma Group The Netherlands B.V.

Responsibilities

Pharmacovigilance Provider

Name

Eresearchtechnology Inc.

Responsibilities

eCOA & Central ECG

Name

Veeva Systems Inc.

Responsibilities

eTMF / CTMS Provider

Name

Aptuit (Verona) S.r.l.

Responsibilities

Samples analysis (PK)

Name

Caris Mpi Inc.

Responsibilities

ctDNA analysis

Third parties

• {"country":"Netherlands","full_name":"Propharma Group The Netherlands B.V.","duties_or_roles":"Pharmacovigilance Provider","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Teiko Bio Inc.","duties_or_roles":"CYTOF analyses","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Oracle France","duties_or_roles":"Data management / IT (sponsor duties codes indicate data/IT functions)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Italy","full_name":"Aptuit (Verona) S.r.l.","duties_or_roles":"Samples analysis (PK)","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Pamgene International B.V.","duties_or_roles":"Kinase profiling on the PBMC samples","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"Manufacturing / product related (product handling)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"eCOA & Central ECG","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Caris Mpi Inc.","duties_or_roles":"ctDNA analysis","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Firalis","duties_or_roles":"Proteomic analysis","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Oncoradiomics","duties_or_roles":"Central Imaging","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"INOVIV","duties_or_roles":"Kinase profiling on the PBMC samples","organisation_type":"Industry"}
• {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"eTMF / CTMS Provider","organisation_type":"Non-Pharmaceutical company"}