E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (NHL) |
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E.1.1.1 | Medical condition in easily understood language |
Non-Hodgkin Lymphoma (NHL) |
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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 | 22.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029547 |
E.1.2 | Term | Non-Hodgkin's 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 |
Dose Escalation: - Determine the MTD with and/or determine the RP2D - Evaluate safety and tolerability of GEN3009
Expansion: -Evaluate (preliminary) anti-tumor efficacy |
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E.2.2 | Secondary objectives of the trial |
Dose Escalation: - Establish PK profile - Evaluate immunogenicity - Evaluate preliminary anti-tumor efficacy - Evaluate preliminary clinical efficacy
Expansion: -Establish PK profile - Evaluate safety and tolerability of GEN3009 - Evaluate clinical efficacy - Evaluate immunogenicity |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Each potential subject must fulfill all of the following criteria to be enrolled in the trial. - Be at least 18 years of age. - Must sign an informed consent form (ICF) prior to any screening procedures. - Has histologically or cytologically confirmed relapsed or refractory B-cell NHL with no available standard therapy or is not a candidate for available standard therapy. - Has 1 of the following B-cell NHL subtypes for the Dose Escalation: o DLBCL, de novo or histologically transformed o HGBCL o PMBCL o FL, with advanced symptomatic disease and with a need for treatment o MCL, without leukemic manifestation o MZL, either nodal, extranodal or mucosa associated, with a need for treatment initiation based on symptoms and/or disease burden o SLL, with a need for treatment based on symptoms and/or disease burden o CLL, with B-cell count < 100x109/L (100,000/µL) in the peripheral blood and presence of measurable lymphadenopathy and/or organomegaly. -Has 1 of the following B-cell NHL subtypes for the Expansion: o DLBCL, de novo or histologically transformed o FL, with advanced symptomatic disease and with a need for treatment initiation o CLL, with B-cell count < 100x109/L (100,000/µL) in the peripheral blood and presence of measurable lymphadenopathy and/or organomegaly. - Has measurable disease for B-cell NHL, or has active disease for CLL (refer to Protocol Section 5.1 for details). - Has Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. - Has acceptable laboratory parameters (refer to protocol for details). - A woman of reproductive potential must agree to use adequate contraception during the trial and for 12 months after the last GEN3009 administration. Adequate contraception is defined as highly effective methods of contraception (refer to Appendix 12 for more information). In countries where 2 highly effective methods of contraception are required, both methods will be required for inclusion and must have a negative serum beta-human chorionic gonadotropin (beta-hCG) at screening. - 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.
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E.4 | Principal exclusion criteria |
Any potential subject who meets any of the following criteria will be excluded from participating in the trial. - Prior treatment with a CD37-targeting agent. - Prior allogeneic hematopoietic stem cell transplantation (HSCT). - Autologous HSCT within 3 months before the first dose of GEN3009. - Treatment with an anti-cancer biologic including anti-CD20 therapy, radio-conjugated or toxin-conjugated antibody or chimeric antigen receptor-T (CAR-T) cell therapy within 4 weeks or 5 half-lives, whichever is shorter, before the first dose of GEN3009. - Chemotherapy or radiation therapy within 2 weeks of the first dose of GEN3009. - Treatment with an investigational drug or an invasive investigational medical device within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of GEN3009. Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy. - Received a cumulative dose of corticosteroids more than the equivalent of 250 mg of prednisone within the 2–week period before the first dose of GEN3009. - Has uncontrolled intercurrent illness (refer to Protocol Section 5.2 for details). - Toxicities from previous anti-cancer therapies have not resolved to baseline levels or to Grade 1 or less except for alopecia and peripheral neuropathy. - Primary central nervous system (CNS) lymphoma or known CNS involvement at screening. - Has known past or current malignancy other than inclusion diagnosis (refer to Section 5.2 for details). - Has had major surgery within 3 weeks before screening or will not have fully recovered from surgery, or has major surgery planned during the time the subject is expected to participate in the trial (or within 4 weeks after the last dose of GEN3009). - Has known history/positive serology for hepatitis B. - Known medical history or ongoing hepatitis C infection that has not been cured. - HIV tested positive at screening. - 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 GEN3009. - Is a man who plans to father a child while enrolled in this trial or within 12 months after the last dose of GEN3009.
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E.5 End points |
E.5.1 | Primary end point(s) |
Dose Escalation: • Rate of DLTs • Frequency and severity of AEs/SAEs • Changes in laboratory parameters • Changes in vital signs
Expansion: • ORR |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During the trial, see protocol |
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E.5.2 | Secondary end point(s) |
Dose Escalation: • PK parameters: clearance, volume of distribution and area under the curve (AUC) at different time points (AUC7days, AUClast and AUCinf), maximum concentration (Cmax), time to Cmax (Tmax), predose trough concentrations (Ctrough), and half-life (T1/2) • Incidence of neutralizing anti-GEN3009 antibodies (ie, anti-drug antibodies [ADAs]) • Objective response rate (ORR) • Complete response rate (CR) • Duration of response (DoR) • Time to response (TTR) • Progression-free survival (PFS) • Overall survival (OS)
Expansion: - PK parameters: clearance, volume of distribution and AUC at different time points (AUC7days, AUClast and AUCinf), Cmax, Tmax, Ctrough, and half-life (T1/2) • Frequency and severity of AEs • Changes in laboratory parameters • Changes in vital signs • CR • DoR • TTR • PFS • OS Incidence of neutralizing anti-GEN3009 antibodies (ie, ADAs) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
During the trial, see protocol |
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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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Different doses of GEN3009 |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 20 |
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 |
France |
Netherlands |
Spain |
United Kingdom |
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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 trial is considered completed when the last subject dies or withdraws from the trial. However, the maximum trial duration is 5 years after the last subject’s first treatment in 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 | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |