A Safety and efficacy study of GEN3009-01 (DuoHexaBody®-CD37) in patients with B-cell Non-Hodgkin Lymphoma
- Conditions
- Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (NHL)MedDRA version: 22.0Level: PTClassification code 10029547Term: Non-Hodgkin's lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-002752-16-ES
- Lead Sponsor
- Genmab Holding B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 120
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 and/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 < 20x109/L (20,000/µL) in the peripheral blood and presence of measurable lymphadenopathy and/or organomegaly.
-Has 1 of the following B-cell NHL subtypes for the Dose 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 < 20x109/L (20,000/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).
- Before the first dose of GEN3009, during the trial, and for 12 months after the last dose of GEN3009, a woman must be either not of childbearing potential or of childbearing potential and practicing a highly effective method of birth control, and must have a negative serum beta-human chorionic gonadotropin (beta-hCG) and urine pregnancy test 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 72
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 48
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Dose Escalation:<br>- Determine the MTD with and/or determine the RP2D<br>- Evaluate safety and tolerability of GEN3009<br><br>Dose Expansion:<br>-Evaluate (preliminary) anti-tumor efficacy;Secondary Objective: Dose Escalation:<br>- Establish PK profile<br>- Evaluate immunogenicity<br>- Evaluate preliminary anti-tumor efficacy<br>- Evaluate preliminary clinical efficacy<br><br>Dose Expansion:<br>-Establish PK profile<br>- Evaluate safety and tolerability of GEN3009<br>- Evaluate clinical efficacy<br>- Evaluate immunogenicity;Primary end point(s): Dose Escalation:<br>• Rate of DLTs<br>• Frequency and severity of AEs/SAEs<br>• Changes in laboratory parameters<br>• Changes in vital signs<br><br>Dose Expansion:<br>• ORR;Timepoint(s) of evaluation of this end point: During the trial, see protocol
- Secondary Outcome Measures
Name Time Method