Overview
The purpose of the dose-escalation part of the trial is to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D), as well as to establish the safety profile of epcoritamab in participants with relapsed or refractory B-cell lymphoma.
In the expansion part, additional participants will be treated with epcoritamab, at the RP2D and the purpose is to further explore and determine the safety and efficacy of epcoritamab.
The dose-OPT part will evaluate alternative priming and intermediate dose regimens of epcoritamab in participants with:
* Diffuse large B-cell lymphoma (DLBCL)
* Follicular lymphoma (FL)
* Mantle cell lymphoma (MCL)
All participants will receive epcoritamab at the RP2D.
Principal investigator
Eligibility criteria
Main Inclusion Criteria - Escalation Part (recruitment completed)
* Documented CD20+ mature B-cell neoplasm 1. DLBCL - de novo or transformed 2. HGBCL 3. PMBCL 4. FL 5. MCL 6. SLL 7. MZL (nodal, extranodal or mucosa associated)
* Relapsed and/or refractory disease following treatment with an anti-CD20 monoclonal antibody (e.g. rituximab) potentially in combination with chemotherapy and/or relapsed after autologous stem cell rescue.
* Eastern Cooperative Oncology Group (ECOG) performance status 0,1 or 2.
* Participants must have measurable disease by CT, MRI or Positron emission tomography-Computed tomography (PET-CT) scan
* Acceptable renal function.
* Acceptable liver function. Main Inclusion Criteria - Expansion \& Dose-OPT Parts
* Documented CD20 positive mature B cell neoplasm or CD20+ MCL.
* DLBCL, de novo or transformed (including double hit or triple hit).
* PMBCL
* FL grade 3B
* Histologic confirmed FL
* MZL
* SLL
* MCL (prior BTKi or intolerant to BTKi)
* At least 2 therapies including an anti-CD20 monoclonal antibody containing chemotherapy combination regimen.
* Either failed prior autologous hematopoietic stem cell transplantation (HSCT) or ineligible for autologous stem cell transplantation due to age or comorbidities.
* At least 1 measurable site of disease based on CT, MRI or PET-CT scan with involvement of 2 or more clearly demarcated lesions and or nodes. Main Exclusion Criteria - All Parts
* Primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening.
* Known past or current malignancy other than inclusion diagnosis.
* AST, and/or ALT \>3 × upper limit of normal.
* Total bilirubin \>1.5 × upper limit of normal, unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin.
* Estimated Creatinine clearance (CrCl) \<45 mL/min.
* Known clinically significant cardiovascular disease.
* Ongoing active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment (excluding prophylactic treatment). Past COVID-19 infection may be a risk factor.
* Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy.
* Seizure disorder requiring therapy (such as steroids or anti-epileptics).
* Any prior therapy with an investigational bispecific antibody targeting CD3 and CD20.
* Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days prior to first epcoritamab administration.
* Eligible for curative intensive salvage therapy followed by high dose chemotherapy with HSCT rescue.
* Autologous HSCT within 100 days prior to first epcoritamab administration, or any prior allogeneic HSCT or solid organ transplantation.
* Active hepatitis B (DNA PCR-positive) or hepatitis C (RNA PCR-positive infection). Participants with evidence of prior HBV but who are PCR-negative are permitted in
* Known human immunodeficiency virus (HIV) infection.
* Exposed to live or live attenuated vaccine within 4 weeks prior to signing Informed consent form (ICF).
* Pregnancy or breast feeding.
* Participant is known or suspected of not being able to comply with the study protocol or has any condition for which, participation would not be in the best interest of the participant.
* Contraindication to all uric acid lowering agents. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
* Documented CD20+ mature B-cell neoplasm 1. DLBCL - de novo or transformed 2. HGBCL 3. PMBCL 4. FL 5. MCL 6. SLL 7. MZL (nodal, extranodal or mucosa associated)
* Relapsed and/or refractory disease following treatment with an anti-CD20 monoclonal antibody (e.g. rituximab) potentially in combination with chemotherapy and/or relapsed after autologous stem cell rescue.
* Eastern Cooperative Oncology Group (ECOG) performance status 0,1 or 2.
* Participants must have measurable disease by CT, MRI or Positron emission tomography-Computed tomography (PET-CT) scan
* Acceptable renal function.
* Acceptable liver function. Main Inclusion Criteria - Expansion \& Dose-OPT Parts
* Documented CD20 positive mature B cell neoplasm or CD20+ MCL.
* DLBCL, de novo or transformed (including double hit or triple hit).
* PMBCL
* FL grade 3B
* Histologic confirmed FL
* MZL
* SLL
* MCL (prior BTKi or intolerant to BTKi)
* At least 2 therapies including an anti-CD20 monoclonal antibody containing chemotherapy combination regimen.
* Either failed prior autologous hematopoietic stem cell transplantation (HSCT) or ineligible for autologous stem cell transplantation due to age or comorbidities.
* At least 1 measurable site of disease based on CT, MRI or PET-CT scan with involvement of 2 or more clearly demarcated lesions and or nodes. Main Exclusion Criteria - All Parts
* Primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening.
* Known past or current malignancy other than inclusion diagnosis.
* AST, and/or ALT \>3 × upper limit of normal.
* Total bilirubin \>1.5 × upper limit of normal, unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin.
* Estimated Creatinine clearance (CrCl) \<45 mL/min.
* Known clinically significant cardiovascular disease.
* Ongoing active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment (excluding prophylactic treatment). Past COVID-19 infection may be a risk factor.
* Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy.
* Seizure disorder requiring therapy (such as steroids or anti-epileptics).
* Any prior therapy with an investigational bispecific antibody targeting CD3 and CD20.
* Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days prior to first epcoritamab administration.
* Eligible for curative intensive salvage therapy followed by high dose chemotherapy with HSCT rescue.
* Autologous HSCT within 100 days prior to first epcoritamab administration, or any prior allogeneic HSCT or solid organ transplantation.
* Active hepatitis B (DNA PCR-positive) or hepatitis C (RNA PCR-positive infection). Participants with evidence of prior HBV but who are PCR-negative are permitted in
* Known human immunodeficiency virus (HIV) infection.
* Exposed to live or live attenuated vaccine within 4 weeks prior to signing Informed consent form (ICF).
* Pregnancy or breast feeding.
* Participant is known or suspected of not being able to comply with the study protocol or has any condition for which, participation would not be in the best interest of the participant.
* Contraindication to all uric acid lowering agents. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
For Referring Providers
Do you have a patient you think would be a good candidate for this trial? Learn more about enrolling your patient.