Safety and Efficacy of GEN3009 (DuoHexaBody®-CD37) in Relapsed or Refractory B-cell Non-Hodgkin Lymphoma – A First-in-Human, Open-label, Phase I/IIa Dose Escalation Trial with Dose Expansion Cohorts

Genmab Holding B.V.0 个研究点目标入组 182 人开始时间: 2020年2月4日最近更新: 2023年10月9日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Genmab Holding B.V.
入组人数: 182

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•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 Bcell 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 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 betahCG 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 and/or GEN3013.
•Are the trial subj

排除标准

•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 protect

研究者

发起方

Genmab Holding B.V.

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