E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diffuse large B-cell lymphoma |
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E.1.1.1 | Medical condition in easily understood language |
Diffuse large B-cell lymphoma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012818 |
E.1.2 | Term | Diffuse large B-cell lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of INCB050465 in terms of objective response rate (ORR) in subjects with relapsed or refractory DLBCL who were not previously treated with a BTK inhibitor (group A). |
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E.2.2 | Secondary objectives of the trial |
• To assess the duration of response (DOR) in subjects who were not previously treated with a BTK inhibitor (group A)
• To assess progression-free survival (PFS) in group A
• To assess overall survival (OS) in group A
• To characterize the safety of INCB050465 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Men and women, aged 18 years or older.
• Relapsed or refractory DLBCL, which has been histologically documented, defined as having received at least 2 but no more than 5 prior treatment regimens (eg, an anti-CD20 antibody, an anti-CD20 antibody with or without chemotherapy, or chemotherapy alone) and ineligible for high-dose chemotherapy supported by autologous stem cell transplant.
• Must have ≥ 1 measurable (≥ 2 cm in longest dimension) or ≥ 1 measurable extranodal lesion (> 1 cm in longest dimension) lesion on computed tomography (CT) scan or magnetic resonance imaging (MRI).
• Subjects must be willing to undergo an incisional or excisional lymph node biopsy of accessible adenopathy or provide the most recent, available archived tumor biopsy.
• Eastern Cooperative Oncology Group performance status 0 to 2. |
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E.4 | Principal exclusion criteria |
• Primary mediastinal (thymic) large B-cell lymphoma.
• Known brain or central nervous system metastases or history of uncontrolled seizures.
• Allogeneic stem cell transplant within the last 6 months, or active graft versus host disease following allogeneic transplant, or autologous stem cell transplant within the last 3 months.
• Use or expected use during the study of any prohibited medications, including potent cytochrome P450 3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is longer) before the first dose of study drug.
• Prior treatment with the following:
− Group A: Prior treatment with a selective phosphatidylinositol 3-kinase (PI3K) δ inhibitor (eg, idelalisib), a pan-PI3K inhibitor, or a BTK inhibitor (eg, ibrutinib).
− Group B: Prior treatment with a selective PI3Kδ inhibitor (eg, idelalisib) or a pan-PI3K inhibitor. |
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E.5 End points |
E.5.1 | Primary end point(s) |
ORR in Group A, defined as the percentage of subjects with a complete response/complete metabolic response (CR/CMR) or partial response/partial metabolic response (PR/PMR) as defined by revised response criteria for lymphomas (Cheson et al 2014), as determined by an Independent Review Committee. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 2 years after the first dose is administered to the last subject enrolled |
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E.5.2 | Secondary end point(s) |
• DOR in Group A, defined as the time from first documented evidence of CR/CMR or PR/PMR until disease progression or death from any cause among subjects who achieve an objective response, as determined by radiographic disease assessment provided by an IRC.
• PFS in Group A, defined as the time from the date of the first dose of study drug until the earliest date of disease progression, as determined by radiographic disease assessment provided by an IRC, or death from any cause.
• OS in Group A, defined as the time from the date of the first dose of study drug until death by any cause.
• Safety as measured by clinical assessments, including vital signs and physical examinations, 12-lead electrocardiograms (ECG), chemistry and hematology laboratory values, and adverse events (AEs). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 2 years after the first dose is administered to the last subject enrolled |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Korea, Republic of |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study will continue up to 2 years after the first dose of study treatment is administered to the last subject enrolled, at which point the study will be closed. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 1 |