NCT06717126进行中（未招募）2 期
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
iOnctura16 个研究点 分布在 3 个国家目标入组 85 人开始时间: 2025年2月27日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 85
- 试验地点
- 16
- 主要终点
- Overall survival
研究概览
简要总结
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?
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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.
排除标准
- •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;
- •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;
- •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;
- •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);
- •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.
研究组 & 干预措施
Arm 1 - Roginolisib 80mg
Experimental
IOA-244: 80 mg (corresponding to 72 mg roginolisib) daily
干预措施: roginolisib (Drug)
Arm 2 - Investigator choice of standard of care
Active Comparator
Investigator´s choice of therapy
干预措施: Investigator choice of standard therapy (Drug)
Arm 3 - Roginolisib 40mg
Experimental
IOA-244: 40 mg (corresponding to 36 mg roginolisib) daily
干预措施: roginolisib (Drug)
结局指标
主要结局
Overall survival
时间窗: 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
To evaluate clinical efficacy of roginolisib as single agent, against Investigator's choice of therapy by assessment of overall survival (OS)
次要结局
- 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)
- Clinical benefit rate (CBR)(Measured at Cycle 5 - approximately 16 weeks from start of dosing)
- Safety and tolerability(Every 4 weeks whilst on treatment anticipated to be 52 weeks)
- Pharmacokinetics (PK)(Every 4 weeks for 52 weeks from start of treatment)
- Safety of 40 vs 80 mg of roginolisib(Every 4 weeks whilst on treatment anticipated to be 52 weeks)
- Health care utilisation(Every 4 weeks whilst on treatment anticipated to be 52 weeks)
- Quality of Life(Every 4 weeks for 52 weeks from start of treatment)
研究者
研究点 (16)
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相关资讯
iOnctura Expands Roginolisib Clinical Trials to US Market with Multi-Cancer Strategy- iOnctura has expanded its roginolisib clinical trial program to the United States, with multiple cancer centers now enrolling patients in Phase II studies for metastatic uveal melanoma and chronic lymphocytic leukemia.
- The company's lead candidate roginolisib, an allosteric modulator of PI3Kδ, demonstrated promising early results including a doubling of overall survival compared to historical controls in uveal melanoma during Phase I trials.
- Dana-Farber Cancer Institute received a substantial US Department of Defense grant to investigate roginolisib in combination with venetoclax and rituximab for relapsed/refractory chronic lymphocytic leukemia patients.
- The drug is being studied across multiple cancer types including non-small cell lung cancer and myelofibrosis, targeting the commonly dysregulated PI3K signaling pathway with potentially improved tolerability over previous PI3Kδ inhibitors.last yeariOnctura Initiates Phase II OCULE-01 Trial of Roginolisib for Metastatic Uveal Melanoma- iOnctura has dosed the first patient in its randomized Phase II OCULE-01 study evaluating roginolisib, an allosteric PI3Kδ modulator, in patients with metastatic uveal melanoma.
- The European Medicines Agency recently granted Orphan Drug Designation for roginolisib, providing 10 years of market exclusivity in the EU, complementing the FDA's ODD designation received in 2023.
- In previous Phase I trials, roginolisib demonstrated excellent safety and doubled overall survival to 16 months in metastatic uveal melanoma patients compared to historical controls.last yeariOnctura's Roginolisib Doubles Overall Survival in Uveal Melanoma Patients- iOnctura's Phase I DIONE-01 study demonstrated clinical activity and long-term safety of roginolisib in uveal melanoma patients.
- Patients treated with roginolisib showed a median overall survival of 16 months, doubling the 7 months seen in historical controls.
- Roginolisib was well-tolerated at the recommended Phase II dose, with minimal Grade 3/4 treatment-emergent adverse events.
- A randomized Phase II OCULE-01 study is underway to further investigate roginolisib in second-line treatment of uveal melanoma.last year