Authorised Phase I and Phase II (Integrated)- Other Chronic Lymphocytic Leukemia

Safety and Efficacy Study of Epcoritamab in Subjects with Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome

EU CTIS ID: 2023-504828-25-00

What this study is testing

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

Phase I and Phase II (Integrated)- Other

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

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.
Inclusion 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 per iwCLL • R/R CLL after receiving at least 2 prior lines of therapy. • Diagnosis of CLL/SLL that meets published diagnostic criteria (Hallek et al., 2018a) • 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 per iwCLL

You likely can't join if

Subject received prior treatment with a CD3×CD20 bsAb.
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.

See the full eligibility criteria

Who can join

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.
Inclusion 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 per iwCLL • R/R CLL after receiving at least 2 prior lines of therapy. • Diagnosis of CLL/SLL that meets published diagnostic criteria (Hallek et al., 2018a) • 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 per iwCLL
Inclusion Criteria Specific to Subjects with R/R CLL – Pirtobrutinib Combination Therapy Safety Run-in CP cohorts and Expansion Arm 4: • Must have active CLL/SLL disease that needs treatment with at least 1 of the criteria being met. • Presence of measurable disease. • Previous treatment with at least one and a maximum 3 prior lines of therapy and must include a covalent BTKi. • Diagnosis of CLL/SLL that meets published iwCLL criteria at the time of diagnosis. • Females of childbearing potential must use highly effective contraceptive measures while taking pirtobrutinib and for 28 days after the last dose. • A woman must agree not to breastfeed a child during treatment and until one week after last dose. • A man who is sexually active with a woman of childbearing potential must use an effective method of contraception during treatment and for 3 months after last dose

What rules you out

Subject received prior treatment with a CD3×CD20 bsAb.
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.
Any of the following active infections: - 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. Known Human T cell leukemia virus infection -Active CMV infection
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
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, 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

The study team makes the final eligibility decision.

Where it's taking place

United Kingdom
United States
Israel
Australia

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include United Kingdom; United States; Israel; Australia. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.