IRB Study Number 23-187
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objective
Tto evaluate the safety of epcoritamab monotherapy without mandatory hospitalization for the first full dose of epcoritamab in subjects with R/R DLBCL or R/R FL Grade 1-3a who have received at least 2 prior lines of systemic anti-lymphoma therapies including at least 1 anti-CD20 monoclonal antibody-containing therapy.
Secondary Objective
Preliminary assessment for overall safety and efficacy of monotherapy of epcoritamab in outpatient setting.
Inclusion Criteria
Consent
- Subjects or their legally authorized representative must voluntarily sign and date an informed consent, approved by an independent ethics committee (IEC)/institutional review board (IRB), prior to the initiation of any screening or study-specific procedures.
Demographic and Laboratory Assessments
Adult male or female, at least 18 years old.
Laboratory values meeting the following criteria within the screening period prior to the first dose of study drug:
Absolute neutrophil count (ANC) ≥ 1.0 × 109/L; growth factor support allowed in case of bone marrow involvement;
Hemoglobin ≥ 8.0 g/dL (Subjects must not have received red blood cell transfusions within 7 days prior to initial Screening);
Platelet count ≥ 75 × 109/L, or ≥ 50 × 109/L in the presence of bone marrow involvement or splenomegaly (Subjects must not have received platelet transfusions within 7 days prior to initial Screening);
Prothrombin Time (PT)/International normalized ratio (INR)/ Activated partial thromboplastin time (aPTT) ≤ 1.5 × upper limit of normal (ULN), unless receiving anticoagulation;
Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 3.0 × upper limit of normal (ULN);
Total bilirubin level ≤ 1.5 × ULN, or ≤ 5 × ULN for subjects with hepatic involvement of disease or of non-hepatic origin. Subjects with Gilbert's syndrome may have total bilirubin levels > 1.5 × ULN, but direct bilirubin must be ≤ 2 × ULN;
Estimated Creatine Clearance (CrCl) ≥ 45 mL/min (as calculated by Cockcroft-Gault Formula, modified as needed for factors such as body weight);
Lymphocyte counts < 5 × 109/L;
Subject is willing and able to comply with procedures required in this protocol.
Subject must be able to tolerate subcutaneous injections.
Subject must have available adequate fresh or paraffin-imbedded tissue at Screening.
Disease/Condition Activity
- Subject meets the following disease activity criteria:
a. R/R Diffuse Large B-cell Lymphoma:
Documented CD20+ mature B-cell neoplasm according to World Health Organization (WHO) classification 20166 or WHO classification 20087 based on representative pathology report;
Diffuse large B-cell lymphoma, NOS (de novo or transformed from FL);
Patients with "double-hit" or "triple-hit" DLBCL (technically classified in WHO 2016 as HGBCL, with MYC and BCL2 and/or BCL6 translocations) Note: Other double-/triple-hit lymphomas are not eligible Relapsed or refractory disease and previously treated with at least 2 prior systemic antineoplastic therapies including at least 1 anti-CD20 monoclonal antibody-containing therapy; Note: Relapsed disease is defined as disease that previously responded to therapy but progressed ≥ 6 months after completion of therapy. Refractory disease is defined as disease that either progressed during therapy, failed to achieve an objective response to prior therapy, or progressed within 6 months after completion of therapy (including maintenance therapy).
Either failed prior autologous hematopoietic stem cell transplantation (HSCT), or ineligible for autologous HSCT due to age, Eastern Cooperative Oncology Group (ECOG) performance status, comorbidities and/or insufficient response to prior treatment;
b. R/R Follicular Lymphoma:
Documented CD20+ mature B-cell neoplasm according to WHO classification 20166 or WHO classification 20087 based on representative pathology report;
Histologic confirmed FL grade 1, 2, or 3a without clinical or pathological evidence of transformation;
Relapsed or refractory disease and previously treated with at least two prior lines of systemic antineoplastic therapies including at least 1 anti-CD20 monoclonal antibody containing therapy; Note: Relapsed disease is defined as disease that previously responded to therapy but progressed ≥ 6 months after completion of therapy. Refractory disease is defined as disease that either progressed during therapy, failed to achieve an objective response to prior therapy, or progressed within 6 months after completion of therapy (including maintenance therapy).
Previously treated with an alkylating agent or lenalidomide;
Relapsed or refractory to the last prior line therapy. Previous lymphoma therapy is defined as 1 of the following: At least 2 months of single-agent therapy, at least 2 consecutive cycles of combination therapy, autologous HSCT, immunomodulatory therapy, or radioimmunotherapy;
- Subject has one or more measurable disease sites:
Fluorodeoxyglucose (FDG)-avid lymphomas: Measurable disease with computerized tomography (CT) (or magnetic resonance imaging [MRI]) scan with involvement of 2 or more clearly demarcated lesions/nodes with a long axis > 1.5 cm and short axis > 1.0 cm (or 1 clearly demarcated lesion/node with a long axis > 2.0 cm and short axis ≥ 1.0 cm) AND FDG positron emission tomography (PET) scan demonstrating positive lesion(s) compatible with CT (or MRI) defined anatomical tumor sites.
FDG-nonavid lymphomas: Measurable disease with CT (or MRI) scan with involvement of 2 or more clearly demarcated lesions/nodes with a long axis > 1.5 cm and short axis > 1.0 cm or 1 clearly demarcated lesion/node with a long axis > 2.0 cm and short axis ≥ 1.0 cm.
- Subject must have an ECOG performance status score 0 – 2.
Subject History
Subject has no history of primary mediastinal lymphoma.
Subject does not have a primary central nervous system (CNS) tumor or known CNS involvement at screening as confirmed by magnetic resonance imaging (MRI)/computed tomography (CT) scan (brain) and, if clinically indicated, by lumbar puncture.
Subject has no history of severe allergic or anaphylactic reactions to anti-CD20 monoclonal antibody therapy.
Subject has no history of an allergic reaction or significant sensitivity to constituents of the study drug (and its excipients) and/or other products in the same class.
Subject has no clinically significant cardiovascular disease, including:
Current or a history of uncontrolled arrhythmia
Current Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification.
Myocardial infarction within 1 year or stroke within 6 months prior to first dose of study drug, or unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV), uncontrolled cardiac arrhythmia (Common Terminology Criteria for Adverse Event [CTCAE] Version 5 Grade 2 or higher) or clinically significant electrocardiogram (ECG) abnormalities (e.g., complete left bundle branch block [CLBBB], third degree conduction block).
- Subject must not have any known past or current malignancy other than inclusion diagnosis, except for:
Cervical carcinoma of Stage 1B or less;
Non-invasive basal cell or squamous cell skin carcinoma;
Non-invasive, superficial bladder cancer;
Prostate cancer with a current prostate-specific antigen (PSA) level < 0.1 ng/mL;
Any curable cancer with a CR of > 2 years duration;
Subject has no clinically significant liver disease, including hepatitis, current alcohol abuse, or cirrhosis.
Subject does not have an active (PCR-positive) Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection. If laboratory evidence for a chronic infection with hepatitis B, close monitoring and prophylactic therapy is required.
Subject has no known history of positive test results confirming Human Immunodeficiency Virus (HIV) infection. Note: HIV testing does not need to be conducted at screening unless it is required per local guidelines or institutional standards.
Subject has no known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) requiring systemic therapy or antibiotics within 2 weeks prior to first dose of study drug.
Subject displays no evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results.
Subject has had no radiation therapy, except for palliative radiation therapy to non-target lesions and must have at least 1 target lesion that has not received radiation therapy.
Subject has had no major surgery within 4 weeks prior to first dose of study drug.
Subject must not have active tuberculosis (TB) or a history of completed treatment for active TB within the past 12 months. Note: Interferon gamma release assay (IGRA) testing does not need to be performed at screening unless active or latent tuberculosis is suspected. For subjects with positive IGRA, active pulmonary tuberculosis must be excluded with clinical evaluation and radiologic imaging. Subjects with positive IGRA and no evidence of active disease may be enrolled after treatment for latent tuberculosis infection (recommendation isoniazid monotherapy for total of 6 months) has been initiated.
Subject has no current autoimmune disease requiring immunosuppressive therapy. Note: If receiving glucocorticoid treatment at screening, must be a maximum daily dose of prednisone 20 mg (or equivalent) and a total of no more than 140 mg over the last 14 days prior to the first dose of study drug.
Subject has no life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
Subject has no current seizure disorder requiring therapy within the last 12 months. Patients with history of seizure disorder must have complete CNS workup.
Subject has no contraindication to all uric acid lowering agents.
Subject has no neuropathy Grade > 1.
Subject has no unresolved toxicities from prior anticancer therapy, defined as having not resolved to CTCAE v 5.0 Grade 0 or 1, with the exception of alopecia.
Subject does not have an active cytomegalovirus (CMV) disease. If preemptive or prophylactic antiviral treatment is initiated, lab eligibility criteria #3 would have to be met on Cycle 1 Day 1. Note: Foscarnet use within 7 days prior to Cycle 1 Day 1 or during Cycles 1 and 2 is prohibited.
Subject has no known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. If a subject has signs/symptoms suggestive of SARS-CoV-2 infection or have had recent known exposure to someone with SARS-CoV-2 infection, they should undergo molecular (e.g., PCR) testing to rule out SARS-CoV-2 infection. Note: SARS-CoV-2 diagnostic tests should be applied following local requirements/recommendations. Subjects who do not meet SARS-CoV-2 infection eligibility criteria must be screen failed and may only rescreen after they meet the following SARS-CoV-2 infection viral clearance criteria:
No signs/symptoms suggestive of active SARS-CoV-2 infection
Negative molecular (e.g., PCR) result
Contraception
For all females of child-bearing potential; a negative serum pregnancy test (beta hCG) at the Screening Visit and a negative urine pregnancy test at baseline prior to the first dose of study drug.
Female subjects of childbearing potential must at least 1 protocol-specified method of birth control, that is effective from 30 days prior to enrollment through at least 12 months after the last dose of study drug. Female subjects of non-childbearing potential do not need to use birth control.
Female who is not pregnant or breastfeeding and is not considering becoming pregnant or donating eggs during the study or for 12 months after the last dose of study drug.
If male, and subject is sexually active with female partner(s) of childbearing potential, he must agree, from 30 days prior to enrollment through 12 months after the last dose of study drug, to practice the protocol-specified contraception.
Male who is not considering fathering a child or donating sperm during the study or for 12 months after the last dose of study drug.
Concomitant Medications
Subject has no active medication known to decrease T-cell numbers or activity or other concurrent immunosuppressive medication within 5 half-lives or 28 days prior to enrollment except for up to 20 mg prednisone daily or equivalent, unless for disease control during screening.
Subject must meet the following criteria regarding time since previous anti-neoplastic agent(s) prior to first dose of study drug:
At least 4 weeks from last dose of non-investigational chemotherapy;
At least 4 weeks or 5 half-lives from last dose of other non-investigational antineoplastic agents, whichever is shorter;
At least 5 half-lives from last dose of investigational agents or 28 days prior to first dose of study drug, whichever is longer;
Subject must not be currently enrolled in another clinical study or was previously enrolled in this study.
Subject has not received prior therapy with an investigational bispecific antibody targeting CD3 and CD20.
Subject has not received vaccination with live vaccines within 28 days prior to first dose of study drug or is expected to need any live vaccination during study participation including at least 3 months following the last dose of study treatment. Note: COVID-19 non-replicating adenoviral vaccines are permitted with a minimum period of 3 days between the vaccine and a dose of study drug.
No Autologous HSCT within 100 days prior to first dose of study drug, or any prior allogeneic HSCT or solid organ transplantation.
No Treatment with CAR-T therapy within 100 days prior to first dose of study drug.
Exclusion Criteria
Exclusion Criteria Not Available
