Phase II study of Roginolisib in UM patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

iOnctura SA

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

25 Feb 2025 → ongoing

Decision date (initial)

2024-12-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To evaluate clinical efficacy of roginolisib, as single agent, against Investigator´s choice of therapy by assessment of OS

Secondary objectives 6

1. To evaluate clinical efficacy of roginolisib, as single agent, using Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 and also using survival probability
2. To further evaluate the safety profile of roginolisib as a single agent
3. To assess the PK concentrations of roginolisib as single agent as single agent, against the predicted 90% inhibition concentration (IC90) levels
4. To assess the Quality of Life (QoL) impact of roginolisib vs Investigator’s choice via patient-reported outcome (PRO)
5. To further evaluate and compare the safety of roginolisib 40 vs 80 mg
6. To assess the health care resource utilisation for patients receiving roginolisib vs Investigator’s choice

Conditions and MedDRA coding

Advanced Metastatic Ocular/Uveal Melanoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

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
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): 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;
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 15

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: 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);
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;, 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;
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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. OS is defined as the time from randomisation until death from any cause.

Secondary endpoints 8

1. • 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; • 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
2. 1. (cont.)• 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; • 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;
3. 1 (cont)• 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; • CBR is defined as the proportion of patients with a BOR of CR or PR or SD recorded at C5D1; • 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.
4. 2. 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;
5. 3. Concentration of roginolisib at pre-dose and steady state levels (including AUC, population PK);
6. 4. 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).
7. 5. 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.
8. 6. Assessed by health resource use (e.g., hospitalisations, outpatient visits, emergency visits, preparation and time for IMP administration, etc)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

iOnctura SA

Sponsor organisation

iOnctura SA

Address

Campus Biotech Innovation Park, Avenue De Secheron 15/f2 Avenue De Secheron 15/f2

City

Geneva

Postcode

1202

Country

Switzerland

Scientific contact point

Organisation

iOnctura SA

Contact name

Michael Lhan

Public contact point

Organisation

iOnctura SA

Contact name

iOnctura team

Third parties 12

Locations

2 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 57 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications