This study has been transitioned to CTIS with ID 2023-504828-25-00 check the CTIS register for the current data. Main objective Monotherapy Cohorts (R/R CLL):• Identify the RP2D and the MTD of epcoritamab• Evaluate the safety and tolerability of…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Monotherapy Cohorts (R/R CLL)
• Incidence of DLTs
• Incidence and severity of AEs and SAEs.
• Incidence and severity of CRS, ICANS and TLS
Monotherapy (R/R CLL [Arm 1] and RS [Arm 2A]):
• ORR as assessed by the IRC
Dose Escalation Venetoclax Combination Therapy (R/R CLL)
• Incidence of DLTs
• Incidence and severity of AEs
Expansion Venetoclax Combination Therapy in R/R CLL (Arm 3)
• ORR as assessed by the IRC
Expansion Lenalidomide Combination Therapy in RS (Arm 2B) and R CHOP
Combination Therapy in RS (Arm 2C)
• ORR as assessed by the IRC
Secondary outcome
• PK parameters (eg, clearance, volume of distribution and AUC0-last
and AUC0-*, Cmax, Tmax, predose values, and t*]
• Pharmacodynamic markers in blood samples
• Incidence of ADAs to epcoritamab
• ORR
• CR/CRi rate
• DOR
• TTR
• PFS
• OS
Monotherapy (R/R CLL [Arm 1] and RS [Arm 2A]), Expansion Lenalidomide
Combination Therapy in RS (Arm 2B) and R CHOP Combination Therapy in RS (Arm
2C):
• DOR
• CR rate (both cohorts)/CRi rate (CLL cohort only)
• PR/nPR rate
• TTR
• PFS
• OS
• TTNT
• Incidence and severity of AEs and SAEs.
• Incidence and severity of CRS, ICANS, and CTLS
• PK parameters (eg, clearance, volume of distribution and AUC0-last and
AUC0-*, Cmax, Tmax, predose values, and t1/2)
• Incidence of overall MRD negativity
• Duration of MRD negativity
• Incidence of ADAs to epcoritamab
Dose Escalation Venetoclax Combination Therapy (R/R CLL)
• ORR
• DOR
• CR/CRi rate
• TTR
• PFS
• OS
• TTNT
• PK parameters (eg, clearance, volume of distribution and AUC0-last and
AUC0-*, Cmax, Tmax, predose values, and t1/2)
• Incidence of overall MRD negativity
• Duration of MRD negativity
• Incidence of ADAs to epcoritamab
Background summary
CLL is a B-cell malignancy characterized by accumulation of clonal
CD5+CD19+CD23+ B cells in the blood and lymphoid organs such as lymph nodes,
spleen, and bone marrow. The median age at CLL diagnosis is 70 years. CLL is
the most common type of leukemia in Western countries accounting for
approximately 25% to 30% of all leukemias in the United States. In the US, an
estimated 21,040 new cases of CLL will be diagnosed in 2020 with 4,060 deaths
expected. Despite significant advances in therapy, CLL remains as an incurable
disease outside of aggressive therapy with stem cell transplantation. Further
development of novel therapies is needed, especially for patients who have had
an early relapse from ibrutinib or venetoclax treatment. Epcoritamab is a fully
human IgG1 bispecific antibody that can induce potent activation and cytotoxic
activity of CD4+ and CD8+ T cells in the presence of CD20-expressing cells and
has shown encouraging clinical data in R/R B-NHL. Patients with CLL may benefit
from epcoritamab in terms of tumor cell reduction, tumor stabilization and/or
improvement of tumor-related symptoms.
Study objective
This study has been transitioned to CTIS with ID 2023-504828-25-00 check the CTIS register for the current data.
Main objective Monotherapy Cohorts (R/R CLL):
• Identify the RP2D and the MTD of epcoritamab
• Evaluate the safety and tolerability of epcoritamab
Expansion Monotherapy (R/R CLL [Arm 1] and RS [Arm 2A]):
• Assess the preliminary efficacy of epcoritamab
Dose Escalation Venetoclax Combination Therapy (R/R CLL)
• Identify the RP2D and the MTD of epcoritamab when coadministered with
venetoclax 400 mg
• Evaluate safety and tolerability of the combination of epcoritamab and
venetoclax
Expansion Venetoclax Combination Therapy in R/R CLL (Arm 3)
• Assess the preliminary antitumor effect of epcoritamab in combination with
venetoclax
Expansion Lenalidomide Combination Therapy in RS (Arm 2B) and R CHOP
Combination Therapy in RS (Arm 2C)
• Assess the preliminary anti tumor effect of epcoritamab in combination with
lenalidomide or R-CHOP
Secondary objectives:
• Characterize the pharmacokinetic properties of epcoritamab
• Evaluate immunogenicity of epcoritamab
• Evaluate safety and tolerability of epcoritamab
• Assess the preliminary anti-tumor activity of epcoritamab
• Assess MRD in blood and marrow
Study design
This is a Phase 1b/2, multi-center, open-label trial investigating the safety,
tolerability, PK, pharmacodynamics, immunogenicity, and preliminary efficacy of
single-agent epcoritamab in subjects with R/R CLL and Richter's Syndrome. The
trial will be conducted in 2 parts: Dose Escalation (Part 1) and Expansion
(Part 2). Each part will consist of a Screening phase (up to 21 days prior to
Cycle 1 Day 1), a Treatment phase (Cycle 1 Day 1 until epcoritamab
discontinuation), and a Follow-up phase (ie, 60-day safety follow-up from the
last dose of epcoritamab and survival follow-up).In the Dose
Escalation, epcoritamab will be tested at 2 full dose levels (ie, 24 mg and 48
mg) using a modified 3+3 design. DLTs will be evaluated during the first
treatment cycle (ie, 28 days). After identifying the RP2D, the preliminary
efficacy of single agent epcoritamab will be
assessed together with safety, tolerability, PK, pharmacodynamics, and
biomarkers in Part 2 (Expansion). Disease evaluation and response assessment
will be performed according to the iwCLL criteria.
Intervention
Epcoritamab will be administered as a SC injection in 4-week cycles (ie, 28
days) as follows: weekly in Cycles 1, 2 and 3; biweekly in Cycles 4 through 9;
and then monthly from Cycle 10 onward until one of the treatment
discontinuation criteria are met. A step-up dosing method will be used: priming
dose on Cycle 1 Day 1 followed by intermediate dose on Cycle 1 Day 8 then full
dose on Cycle 1 Day 15 and Day 22 and in subsequent doses. A Dose Escalation
Committee (DEC) and A Data Monitoring Committee (DMC) will assess the safety
per individual charter.
Study burden and risks
Treatment with epcoritamab involves subcutaneous injection (the first 4 visits
followed by hospitalization and premedication). Risks associated with
participation are side effects, among which tumor lysis syndrome, cytokine
release syndrome and neurological symptoms (ICANS).
The risk to subjects in this trial should be minimized by compliance with the
eligibility criteria, trial procedures, close monitoring, and proper/prompt
management of TEAEs.
The patients will need to follow appointments for visits and will undergo
physical examination, ECOG, neurological evaluation (ICANS), ECG,
venapunctions, scans and biopsies. Patients will be interviewed on past and
present medical conditions, diseases, surgeries, allergies and previous
medicines. Also, patients should not become pregnant, breastfeed a baby,
father a child or donate sperm or eggs while participating in this trial and
must agree to use a highly effective method of birth control from the time of
screening until 12 months after the last dose of epcoritamab. Patients will be
tested for hepatitis B, C and cytomegalovirus, HIV.
The GCT3013-03 trial population is limited to subjects with R/R CLL who have
exhausted (or cannot tolerate) standard therapies and therefore have limited
treatment options left. Based on encouraging clinical data in R/R B-NHL,
epcoritamab has the potential to address the highly unmet medical need in R/R
CLL. CLL is a B-cell neoplasm and patients with CLL may benefit from
epcoritamab in terms of tumor cell reduction, tumor stabilization and/or
improvement of tumor-related symptoms. With safety precautions and close
monitoring plan in place, the described risks are outweighed by the potential
benefit subjects might receive from epcoritamab.
More detailed information about the known and expected benefits and risks and
reasonably
expected AEs of epcoritamab are found in the IB.
Carl Jacobsen Vej 30
Valby DK-2500
DK
Carl Jacobsen Vej 30
Valby DK-2500
DK
Listed location countries
Age
Inclusion criteria
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 in a sample representative of the disease (eg,
tumor biopsy/peripheral blood/bone arrow) at Screening
• Has acceptable laboratory parameters
• 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 (betahCG)
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.
Criteria Specific to Subjects With R/R CLL- Dose Escalation Monotherapy (All
Cohorts) and Expansion Monotherapy (Arm 1)
• Must have active CLL/SLL disease that needs treatment.
• R/R CLL after receiving at least 2 prior lines of therapy.
• Diagnosis of CLL/SLL that meets published diagnostic criteria
• Must take prophylaxis for TLS
Inclusion Criteria Specific to Subjects With Richter's Syndrome - Expansion
Monotherapy Arm 2A
• Must have measurable disease as determined by FDG- PET CT and a CT scan (or
MRI)
• Must provide a mandatory FFPE tumor tissue sample;
Inclusion Criteria Specific to Subjects With Richter's Syndrome - Lenalidomide
Combination Therapy Expansion Arm 2B
• Have tumor biopsy-proven CD20+ DLBCL and a clinical history of CLL/SLL.
• Deemed as ineligible for chemoimmunotherapy
• Eligible for treatment with lenalidomide.
• Must have measurable disease as determined by FDG- PET CT and a CT scan (or
MRI)
• Must provide a mandatory FFPE tumor tissue sample;
• Females of childbearing potential must use 2 forms of contraception
• A woman of childbearing potential must have a negative serum (betahCG)
pregnancy test
• Males must always use a latex or synthetic condom during any sexual contact
with females of reproductive potential while taking lenalidomide
Inclusion Criteria Specific to Subjects With Richter's Syndrome - R-CHOP
Combination Therapy Expansion Arm 2C
• Have tumor biopsy-proven CD20+ DLBCL and have a clinical history of CLL/SLL.
• Eligible to receive R-CHOP per investigator determination.
• Must have measurable disease as determined by FDG- PET CT and a CT scan (or
MRI)
• Must provide a mandatory FFPE tumor tissue sample;
Inclusion Criteria Specific to Subjects with R/R CLL - Venetoclax Combination
Therapy Dose Escalation Cohorts and Expansion Arm 3
• Must have active CLL/SLL disease that needs treatment
• At least 1 of the following disease-related (constitutional) symptoms:
• Unintentional weight loss >= 10% within the previous 6 months
• Significant fatigue
Exclusion criteria
All Subjects • Subject received prior treatment with a CD3×CD20 bsAb. • Subject
received any prior allogeneic HSCT or solid organ transplantation • Subject
received treatment with an anticancer agent, as follows: - 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 • Uncontrolled autoimmune hemolytic anemia or immune
thrombocytopenia (requiring >20 mg of prednisolone daily) or other concurrent
uncontrolled medical conditions. • Unstable or uncontrolled disease/condition
related to or affecting cardiac function, eg, unstable angina, congestive heart
failure grade III or IV as classified by the New York Heart Association (see
Appendix 3), uncontrolled clinically significant cardiac arrhythmia (CTCAE v5.0
grade 2 or higher), or clinically significant ECG abnormalities • Myocardial
infarction, intracranial bleed, or stroke within the past 6 months • Subject
age >=75 and 2 or more active grade >=2 cardiovascular conditions. • Subject has
toxicities from previous anticancer therapies that have not resolved to
baseline levels or to grade 1 or less except for alopecia and peripheral
neuropathy • Subject has history or presence of clinically relevant disorder
affecting the CNS • ICE score of less than 8 at study entry • Subject has known
past or current malignancy other than inclusion diagnosis, except for: a.
Cervical carcinoma of Stage 1B or less b. Non-invasive basal cell or squamous
cell skin carcinoma c. Non-invasive, superficial bladder cancer d. Prostate
cancer with a current PSA level <0.1 ng/mL e. Any curable cancer with a CR of
>2 years duration • Subject has suspected allergies, hypersensitivity, or
intolerance to epcoritamab or another anti-CD20 mAb or its excipients (refer to
the IB for more information). • Active HBV (DNA PCR-positive). Subjects with
evidence of prior HBV but who are PCR-negative are permitted in the trial but
should receive prophylactic antiviral therapy. • Active hepatitis C (RNA
PCR-positive infection). Subjects who received treatment for HCV that was
intended to eradicate the virus may participate if hepatitis C RNA levels are
undetectable • Subject is a woman who is pregnant or breastfeeding, 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-504828-25-00 |
| EudraCT | EUCTR2020-000848-57-NL |
| CCMO | NL74221.056.20 |