E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed, progressive and/or refractory mature B-cell lymphoma Patients with: - Diffuse large B-cell lymphoma – de novo or transformed - High-grade B-cell lymphoma - Primary mediastinal large B-cell lymphoma - Follicular lymphoma - Mantle cell lymphoma - Small lymphocytic lymphoma - Marginal zone lymphoma (nodal, extranodal or mucosa associated) |
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E.1.1.1 | Medical condition in easily understood language |
Lymphoma of B-cell origin |
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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 | 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) |
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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 |
Escalation Phase: - Determine maximum tolerated dose and recommended phase 2 dose
Expansion Phase: - To evaluate clinical efficacy as determined by Lugano criteria
Optimization part: - - to determine whether an alternative priming/intermediate dose regimen may reduce CRS risk |
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E.2.2 | Secondary objectives of the trial |
Escalation Phase: - Establish tolerability of epcoritamab - Establish PK profile after single and multiple doses - Evaluate immunogenicity - Evaluate anti-lymphoma activity
Expansion and Optimization Part: - To further evaluate clinical efficacy as determined by Lugano criteria - To evaluate clinical efficacy as determined by Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) - To further evaluate clinical efficacy - To evaluate MRD status as a clinical efficacy endpoint - To evaluate safety and tolerability of epcoritamab - To evaluate the PK and immunogenicity of epcoritamab - To evaluate patient-reported outcomes (PROs) related to lymphoma symptoms -To evaluate safety and tolerability of alternative priming/intermediate dosing regimens |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient must be 18 years of age or older (for expansion: In countries where the legal age is 21 years of age; only patients 21 years of age or older are eligible) 2. Documented CD20+ mature non-Hodgkin B-cell lymphoma according to WHO classification 3. Relapsed, progressive and/or refractory disease (Cheson et al., 2007) following treatment with an anti-CD20 monoclonal antibody 4. Patients must have received at least 2 prior lines of therapy 5. Patients must have measurable disease by imaging 6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 (2 for escalation) 7. For the optimization part, patients must have R/R DLBCL, or FL grades 1-3A, or MCL (according to cohort).
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E.4 | Principal exclusion criteria |
1. Primary central nervous system (CNS) lymphoma or known CNS involvement by lymphoma 2. AST, and/or ALT > 3 x upper limit of normal 3. Total bilirubin > 1.5 x upper limit of normal 4. Creatinine clearance < 45 mL/min 5. Known clinically significant cardiac disease, including: a. Onset of unstable angina pectoris within 6 months of signing ICF b. Acute myocardial infarction within 6 months of signing ICF c. Congestive heart failure (grade III or IV as classified by the New York Heart Association and/or known decrease ejection fraction of < 45% 6. Ongoing active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment (excluding prophylactic treatment) at the time of enrolment or within the previous 2 weeks prior to the first dose of epcoritamab, including COVID-19 infection. 7. Eligible for curative salvage therapy with high dose therapy followed by stem cell rescue 8. Active hepatitis B (DNA PCR-positive) or hepatitis C (RNA PCR positive infection). Subjects with evidence of prior HBV but who are PCRnegative are permitted in the trial but should receive prophylactic antiviral therapy. 9. Known human immunodeficiency virus (HIV) infection 10. Exposed to live or live attenuated vaccine within 4 weeks prior to signing ICF 11. Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days prior to first GEN3013 administration 12. Autologous HSCT within 100 days prior to first GEN3013 administration, or any prior allogeneic HSCT or solid organ transplantation 13. Contraindication to all uric acid lowering agents
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E.5 End points |
E.5.1 | Primary end point(s) |
Escalation End Points: - Dose limiting toxicity - Adverse events
Expansion End Points: - Overall response rate (ORR) determined by Lugano criteria as assessed by independent review committee (IRC)
Optimization End Points: - Adverse events; Rating of ≥ Grade 2 CRS events |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- DLT evaluation period is defined as the first 4 weeks, i.e. 28 days after the first administration of GEN3013. - AE evaluation will be done at each visit during the entire study
- Rate of ≥ Grade 2 CRS events and all grade CRS events from first dose of epcoritamab through 7 days following administration of the second full dose of epcoritamab |
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E.5.2 | Secondary end point(s) |
Escalation End Points: - Cytokine measures - Laboratory parameters (biochemistry, hematology including immunophenotyping for absolute T-cell and B-cell counts as well as T-cell activation and exhaustion markers) - PK parameters (clearance, volume of distribution and area-under-the concentration- time curve (AUC0-Clast and AUC0-∞), maximum concentration (Cmax), time of Cmax (Tmax), pre dose values, and half-life) - Immunogenicity of GEN3013 - Anti-lymphoma activity, i.e. resolution of constitutional symptoms, reduction in tumor size, objective and best response - Duration of response - Progression free survival - Time to next anti-lymphoma therapy - Overall survival
Expansion Efficacy End Points per IRC and Optimization Efficacy End Points per Investigator: - Duration of response (DOR) determined by Lugano criteria - Complete response (CR) rate determined by Lugano criteria - Duration of CR (DoCR) by Lugano criteria - Progression-free survival (PFS) determined by Lugano criteria - Time to response (TTR) determined by Lugano criteria - Objective and best response rate determined by Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) - PFS determined by LYRIC - DOR determined by LYRIC - DoCR determined by LYRIC - TTR determined by LYRIC - Overall survival (OS) - Time to next (anti-lymphoma) therapy (TTNT) - Rate of MRD negativity - MRD status by detection of cancer cell gene sequences - Safety (i.e., adverse events, laboratory parameters [biochemistry, hematology including immunophenotyping for absolute T-cell and B-cell counts as well as T-cell activation and exhaustion markers], hospitalizations, and cytokine measures) - PK parameters (clearance, volume of distribution, Cmax, Tmax, trough concentrations, and half-life) and incidence of ADAs to GEN3013 - Changes in lymphoma symptoms as measured by the Functional Assessment of Cancer Therapy – Lymphoma (FACT-Lym) - Rate of ≥ Grade 2 CRS events and all grade CRS events following first full dose Rate of ≥ Grade 2 CRS events and all grade CRS events overall
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | 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 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
Singapore |
Australia |
Canada |
Denmark |
Finland |
France |
Germany |
Italy |
Korea, Republic of |
Netherlands |
Poland |
Spain |
Sweden |
United Kingdom |
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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Last patient last visit; The trial will run for a maximum of 5 years after the last patient's first dose. The final data from the trial site will be sent to the sponsor (or designee) after completion of the final patient visit within the time frame specified in the clinical trial agreement. |
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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 | 10 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 10 |