Safety and Efficacy Study of Epcoritamab in Subjects with Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter’s Syndrome
- Conditions
- Chronic Lymphocytic LeukemiaMedDRA version: 21.0Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-000848-57-CZ
- Lead Sponsor
- Genmab A/S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 96
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
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 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 76
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • Identify the RP2D and the MTD of epcoritamab <br>• Evaluate the safety and tolerability of epcoritamab ;Secondary Objective: • Characterize the pharmacokinetic properties of epcoritamab<br>• To evaluate pharmacodynamic markers linked to efficacy and mechanism of action of epcoritamab <br>• Evaluate immunogenicity of epcoritamab<br>• Assess the preliminary anti-tumor activity of epcoritamab <br>;Primary end point(s): • Incidence of DLTs <br>• Incidence and severity of AEs and SAEs. <br>• Incidence and severity of CRS, ICANS and TLS<br>• Incidence of dose interruption, dose delay, and dose intensity<br>;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.<br>For the other end points, please refer to protocol
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • PK parameters (eg, clearance, volume of distribution and AUC0-last and AUC0-8, Cmax, Tmax, predose values, and t½)<br>• Pharmacodynamic markers in blood samples<br>• Incidence of ADAs to epcoritamab<br>• ORR <br>• CR/CRi rate<br>• DOR <br>• TTR<br>• PFS<br>• OS<br>;Timepoint(s) of evaluation of this end point: please refer to protocol