E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Lymphocytic Leukemia |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Lymphocytic Leukemia |
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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 | LLT |
E.1.2 | Classification code | 10008976 |
E.1.2 | Term | Chronic lymphocytic leukemia |
E.1.2 | System Organ Class | 100000004864 |
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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 |
• Identify the RP2D and the MTD of epcoritamab • Evaluate the safety and tolerability of epcoritamab |
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E.2.2 | Secondary objectives of the trial |
• Characterize the pharmacokinetic properties of epcoritamab • Characterize the pharmacodynamic properties of epcoritamab • Evaluate immunogenicity of epcoritamab • Assess the preliminary anti-tumor activity of epcoritamab
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All Subjects • Subject must sign an ICF, prior to any screening procedures • Must be at least 18 years of age • ECOG performance status score of 0,1 or 2 • Evidence of CD20 positivity at screening • Has acceptable laboratory parameters • Subject must have availability of fresh bone marrow material at screening • A woman with reproductive potential must agree to use adequate contraception during the trial, and for 12 months after the last administration of epcoritamab. • A woman of childbearing potential must have a negative serum (beta hCG) pregnancy test at screening and a negative serum or urine pregnancy test before treatment administration on Day 1 of every cycle. • A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the entire trial, until 12 months after last treatment. • A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control.
Inclusion Criteria Specific to the R/R CLL Cohort • Must have active CLL disease that needs treatment •R/R CLL after receiving at least 2 prior lines of systemic antineoplastic therapy • Has measurable disease with at least one of the following criteria: a. =5 × 109/L (5,000/µL) B lymphocytes in peripheral blood b. Presence of measurable lymphadenopathy and/or organomegaly • Must take prophylaxis for TLS
Inclusion Criteria Specific to the Richter's Syndrome Cohort • Must have a clinical history of CLL/SLL with biopsy-proven transformation toward aggressive lymphoma (ie, DLBCL subtype). • Deemed as ineligible for chemoimmunotherapy at investigator's discretion or refuse to receive intensive chemotherapy. • Must have measurable disease |
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E.4 | Principal exclusion criteria |
All Subjects • Subject received prior treatment with a CD3 × CD20 bispecific antibody. • Subject received any prior allogeneic HSCT or solid organ transplantation • Subject received treatment with an anti-cancer agent, eg: a. Small molecules such as BTK inhibitor, BCL2 inhibitor, or PI3K inhibitor within 5 half-lives prior to the first dose of epcoritamab; or b. Anti-CD20 mAb or chemotherapy within 2 weeks prior to the first dose of epcoritamab; or c. Radio-conjugated or toxin conjugated antibody or CAR-T cell therapy within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of epcoritamab d. Subject received treatment with an investigational drug, within 4 weeks or 5 half-lives, whichever is shorter prior to the first dose of epcoritamab. • Subject has autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy. • Subject has clinically significant cardiac disease • Subject received vaccination with live vaccines within 28 days prior to the first dose of epcoritamab • Subject has known central nervous system (CNS) involvement at screening. • Has had major surgery within 4 weeks prior to enrollment. • Known medical history or ongoing hepatitis C infection that has not been cured. • Known history of seropositivity for HIV infection. Note: HIV testing is required at screening only if required per local health authorities or institutional standards. • Subject is a woman who is pregnant or breast-feeding, or who is planning to become pregnant while enrolled in this trial or within 12 months after the last dose of epcoritamab. • Subject is a man who plans to father a child while enrolled in this trial or within 12 months after the last dose of epcoritamab. • Subject has uncontrolled intercurrent illness, such as ongoing or active infection requiring intravenous antibiotics treatment at the time of enrollment or within the previous 2 weeks prior to the first dose of epcoritamab.
Exclusion Criteria Specific to the R/R CLL Cohort (numbering continues as per Protocol) • Any history of RS or evidence indicating a potential Richter's transformation. • Subject is unable to tolerate uric acid reducing medications.
Exclusion Criteria Specific to the Richter's Syndrome Cohort • Diagnosis of Richter's syndrome not of the DLBCL subtype such as Hodgkin's lymphoma, prolymphocytic leukemia. • Subject received autologous HSCT within 3 months prior to the first dose of epcoritamab. • Subject received more than 1 prior line of therapy for RS. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Incidence of DLTs • Incidence and severity of AEs and SAEs. • Incidence and severity of CRS, ICANS and TLS • Incidence of dose interruption, dose delay, and dose intensity
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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, ie, 28 days after the first administration ofepcoritamab. For the other end points, please refer to protocol |
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E.5.2 | Secondary end point(s) |
• PK parameters (eg, clearance, volume of distribution and AUC0-last and AUC0-∞, Cmax, Tmax, predose values, and t½] • Pharmacodynamic markers in blood samples • Incidence of ADAs to epcoritamab • ORR • CR/CRi rate • DOR • TTR • PFS • OS
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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 | 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) | 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 |
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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.8.2.4 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 |
Belgium |
Denmark |
Germany |
Netherlands |
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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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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |