E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003903 |
E.1.2 | Term | B-cell lymphoma refractory |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003917 |
E.1.2 | Term | B-cell type acute leukaemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10026945 |
E.1.2 | Term | Mature B-cell type acute leukaemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067184 |
E.1.2 | Term | Burkitt's leukaemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003890 |
E.1.2 | Term | B precursor type acute leukaemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020267 |
E.1.2 | Term | Hodgkin's disease refractory |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020266 |
E.1.2 | Term | Hodgkin's disease recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003902 |
E.1.2 | Term | B-cell lymphoma recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to assess safety, tolerability and dose limiting toxicity (DLT) of:
• Single-agent REGN2810 in patients with lymphoma (B-cell non-Hodgkin lymphoma [B-NHL] and Hodgkin's lymphoma [HL])
• Combination REGN1979 and REGN2810 in patients with B NHL
|
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are:
• To determine a recommended dose for:
o cemiplimab as a single-agent in patients with lymphoma (B-NHL and
HL)
o REGN1979 and cemiplimab administered in combination in patients with B-NHL.
• To characterize the pharmacokinetic (PK) profile of cemiplimab when
administered as a single agent and of cemiplimab and REGN1979 when
administred in combination
• To assess the immunogenicity of cemiplimab when administered alone
and the immunogenicity of cemiplimab and REGN1979 when administred in combination
• To study the preliminary antitumor activity of cemiplimab as a single
agent and of the combination of cemiplimab and REGN1979 in specific
indications, as measured by overall response rate, minimal residual
disease (MRD) in patients with bone marrow disease at baseline, duration of response and median progression-free survival and rates at 6 and 12 months |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1-Principal Inclusion Criteria for B-NHL and HL Treatment Arms:
Hematologic malignancy defined by either:
a. NHL: Documented CD20+ B-cell malignancy, with active disease that is either refractory to or relapsed after most recent prior therapy, for whom no standard of care options exist, and for whom treatment with an anti-CD20 antibody may be appropriate:
i. B-NHL per WHO 2008 criteria (Campo 2011)
b. Documented HL, per WHO 2008 criteria (Campo 2011), with active disease not responsive to prior therapy or relapsed after prior therapy for whom no standard of care options exist (cemiplimab single agent therapy cohorts ONLY)
All patients must have at least one bi-dimensionally measurable lesion (≥1.5 cm) documented by diagnostic imaging (CT, PET-CT, or MRI).
Eastern Cooperative Oncology Group (ECOG) performance status ≤1. Note: Individual cases of patients with ECOG 2 performance status may be discussed with the medical monitor for potential enrollment.
Age ≥18 years
Adequate bone marrow function documented by:
a. Platelet counts ≥75 x 109/L
b. Hb level ≥9 g/dL
c. ANC ≥1 x 109/L
Adequate hepatic function:
a. Total bilirubin ≤1.5 x ULN (≤3 x ULN if liver involvement)
b. Transaminases ≤2.5 x ULN (≤5 x ULN if liver involvement)
c. Alkaline phosphatase (ALP) ≤2.5 x ULN (≤5 x ULN if liver involvement) |
|
E.4 | Principal exclusion criteria |
1-Principal Exclusion Criteria for B-NHL and HL Treatment Arms
Primary central nervous system (CNS) lymphoma, or known or suspected CNS involvement by non-primary CNS NHL
History of or current relevant CNS pathology
Ongoing or recent (within 2 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for iAEs
History of treatment-related iAEs from immune-modulatory agents
Standard or investigational anti-neoplastic therapy (nonbiologic) within 5-times the half life or within 28 days, whichever is shorter, prior to first administration of study drug
Standard radiotherapy within 14 days of first administration of study drug
Treatment with alemtuzumab within 12 weeks prior to first administration of study drug(s)
Treatment with rituximab, immune-modulating agents or other investigational or commercial biologic agent less than 28 days prior to first administration of study drug(s).
Prior allogeneic stem cell transplantation
Prior treatment with an agent that blocks the PD-1/PD-L1 pathway, unless the patient demonstrated benefit (applicable only for patients in single-agent REGN2810 therapy)
Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection; or other uncontrolled infection. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From informed consent form signature until 30 day post last dose of study drug |
|
E.5.2 | Secondary end point(s) |
• PK of single agent cemiplimab , and PK of REGN1979 and cemiplimab when given in combination
• Antitumor activity:
o Overall response rate (ORR) as per applicable response criteria for the indication
o Duration of response, and PFS at 6 and 12 months
o Minimal residual disease (MRD) for patients with bone marrow involvement at baseline
• Pharmacodynamic measures including:
o Cytokine profiling
o Peripheral blood B-cell and T-cell subsets and immune phenotyping
o Analysis of PD-1 receptor occupancy of circulating T-cells
o Changes in gene expression in peripheral blood
o Serum immunoglobulin
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
each of the secondary endpoints is being assessed at specific time points as outlined in protocol |
|
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
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 | No |
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.8.3 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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 |
United States |
Spain |
Germany |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
The end of study is defined as the time when the last patient has completed all study visits, including follow-up. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 9 |