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-DK
- Lead Sponsor
- Genmab Holding B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 182
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
o For the dose escalation: with no available standard therapy or is not a candidate for available standard therapy. All subjects must have received at least 2 prior lines of systemic therapy, and,
a. For all indolent NHL (FL, MZL, and SLL) as well as aggressive NHL (DLBCL, HGBCL, and PMBCL), at least 1 of the 2 prior lines of treatment must have been a CD20-containing systemic regimen;
b. For MCL, subjects must have had or are otherwise ineligible for treatment with a BTK inhibitor, and;
c. For CLL, subjects must have received at least 1 prior line of BTK inhibitor or BCL-2 inhibitor.
o For the expansion (including Safety Run-in): All subjects must have received at least 2 prior lines of systemic therapy, and,
a. For FL and DLBCL, at least 1 of the 2 prior lines of treatment must have been a CD20-containing systemic regimen;
b. For CLL, subjects must have received at least one prior line of BTK inhibitor or BCL-2 inhibitor.
- 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 active disease that needs treatment based on the International Workshop on Chronic Lymphocytic Leukemia [iwCLL] criteria)
and the following B-cell NHL subtypes for the Expansion (including safety run-in):
o DLBCL, de novo or histologically transformed
o FL Grade 1, 2 and 3a, with advanced symptomatic disease and with a need for treatment initiation
o CLL, must have active disease that needs treatment with at least 1 of the following criteria being met:
a. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia
b. Massive (ie, =6 cm below the left costal margin) or progressive or symptomatic splenomegaly
c. Massive nodes (ie, =10 cm in longest diameter) or progressive or symptomatic lymphadenopathy
o GEN3009 + GEN3013 combination cohort only: Documented CD20+ DLBCL or FL based on representative pathology report
- Has measurable disease for B-cell NHL or for CLL.
- Has ECOG performance status of 0 or 1.
- Has acceptable laboratory parameters.
- A woman of reproductive potential must agree to use adequate contraception during the trial and for 12 months after the last GEN3009 and/or GEN3013 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.
- A woman of childbearing potential must have a negative serum 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 and all men must also not donate sperm during the trial and for 12 months after receiving the last dose of GEN3009 an
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.
- For the Expansion (including safety run-in): GEN3009 + GEN3013 combination cohort only: Prior treatment with a CD3 × CD20 bispecific antibody.
- Prior allogeneic HSCT.
- Autologous HSCT within 3 months before the first dose of GEN3009.
- For the Expansion (including safety run-in): Lymphomas leukemia phase: high absolute lymphocyte count or the presence of abnormal cells in the peripheral blood indicating circulating lymphoma cells
- Treatment with an anti-cancer biologic including anti-CD20 therapy, radio-conjugated or toxin-conjugated antibody or chimeric antigen receptor (CAR) T cell therapy within 4 weeks or 5 half-lives, whichever is shorter, before the first dose of GEN3009. Treatment with small molecules such as BTK inhibitors, BCL2 inhibitors, or PI3K inhibitors within 5 half-lives prior to 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, and at any time during the study treatment period.
- 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).
- For the Expansion (including safety run-in): GEN3009 + GEN3013 combination cohort only: Seizure disorder requiring therapy (such as steroids or anti-epileptics)
- 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).
- Had allergic reactions to anti-CD20 or anti-CD37 monoclonal antibody treatment or intolerant to GEN3009 excipients (refer to the GEN3009 IB for more information).
- For the Expansion (including safety run-in): Intolerant to GEN3013 excipients (refer to the GEN3013 IB for more information).
- Has had major surgery, (eg, requiring general anesthesia) within 4 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 and/or GEN3013).
- Has known history/positive serology for hepatitis B.
- Known medical history or ongoing hepatitis C infection that has not been cured.
- Known history of seropositivity for HIV infection.
- 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 and/or GEN3013.
- Is a man who plans to father a child while enrolled in this trial or within 12 months after the last dose of GEN3009 and/or GEN3013.
- Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. Additionally, vulnerable subjects or subjects under guardianship, curatorship, judicial protectio
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method