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Clinical Trial 20751

Cancer Type: Malignant Hematology
Study Type: Treatment
NCT#: NCT03625037

Phase: Phase I/II
Principal Investigator: Chavez, Julio

Call 813-745-6100
or 1-800-679-0775 Learn More

Overview

Study Title

A Phase 1/2, Open-Label, Dose-Escalation Trial of GEN3013 in Patients with Relapsed, Progressive or Refractory B-Cell Lymphoma

Summary

The trial is an open-label, multi-center safety trial of epcoritamab GEN3013 (DuoBody®-CD3xCD20). The trial consists of two parts: a dose escalation part phase 1, first-in-human (FIH) and an expansion part phase 2a. The purpose of the escalation part of the trial is to determine the maximum tolerated dose and the recommended phase 2 dose (RP2D) as well as to establish the safety profile of epcoritamab GEN3013 (DuoBody®-CD3xCD20) in patients with relapsed, progressive or refractory B-Cell Lymphoma. In the expansion part additional patients will be treated with epcoritamab with the RP2D and the purpose is to further explore and determine the safety and efficacy of epcoritamab.

Objective

Dose Escalation Objectives: Primary: -Determine maximum tolerated dose and recommended phase 2 dose Secondary: -Establish tolerability of GEN3013 -Establish PK profile after single and multiple doses -Evaluate immunogenicity -Evaluate anti-lymphoma activity Exploratory: -To evaluate biomarkers predictive of clinical response to GEN3013 -To evaluate pharmacodynamic markers linked to the mechanism of action of GEN3013 Expansion Objectives: Primary -To evaluate clinical efficacy as determined by Lugano criteria Secondary: -To further evaluate clinical efficacy as determined by Lugano criteria -To evaluate anti-lymphoma activity as determined by Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) -To further evaluate clinical efficacy -To evaluate MRD status as a clinical efficacy endpoint -To evaluate safety and tolerability GEN3013 -To evaluate the PK and immunogenicity of GEN3013 -To evaluate patient-reported outcomes (PROs) related to lymphoma symptoms Exploratory: -To evaluate biomarkers predictive of clinical response to GEN3013 -To evaluate pharmacodynamic markers linked to the mechanism of action of GEN3013 -To evaluate PROs related to well-being and general health status

Treatments

Therapies

Cell Therapy

Medications

GEN3013 (Epcoritamab)

Inclusion Criteria

Main Inclusion Criteria Escalation Part

Documented CD20+ mature B-cell neoplasm (1) Diffuse large B-cell lymphoma - de novo or transformed (2) High-grade B-cell lymphoma (3) Primary mediastinal large B-cell lymphoma (4) Follicular lymphoma (5) Mantle cell lymphoma (6) Small lymphocytic lymphoma (7) Marginal zone lymphoma (nodal, extranodal or mucosa associated)

Relapsed, progressive 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.

ECOG performance status 0,1 or 2

Patients must have measurable disease by CT, MRI or PET-CT scan

Acceptable renal function

Acceptable liver function Main Inclusion Criteria Expansion and Optimization Part

Documented CD20 positive mature B cell neoplasm or CD20+ MCL

Diffuse large B cell lymphoma, de novo or transformed (including double hit or triple hit)

Primary mediastinal large B cell lymphoma

Follicular lymphoma grade 3B

Histologic confirmed follicular lymphoma

Marginal zone lymphomas

Small lymphocytic lymphoma

Mantle Cell Lymphoma (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 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

Criterion applies to optimization part patients only: patients must have documented CD20+ DLBCL, NOS (de novo or transformed from FL) (for DLBCL cohort), FL Grade 1, 2, or 3A (for FL cohort), or, only if cohort is opened: MCL (for MCL cohort), according to WHO 2016 classification (Swerdlow et al., 2016).

Other criteria apply

Exclusion Criteria

Expansion Exclusion Criteria:

Primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening as confirmed by mandatory magnetic resonance imaging (MRI)/computed tomography (CT) scan (brain) and, if clinically indicated, by lumbar puncture.

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 2 years duration

AST, and/or ALT >3x upper limit of normal

Total bilirubin >1.5x upper limit of normal

Creatinine clearance > Known clinically significant cardiac disease

Chronic ongoing infectious diseases requiring treatment (excluding prophylactic treatment) at the time of enrolment or within the previous 2 weeks prior to the first dose of GEN3013

Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy. Low-dose (≤10 mg/day) prednisolone (or equivalent) for rheumatoid arthritis or similar conditions is allowed

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 GEN3013 administration

Eligible for curative intensive salvage therapy followed by high dose chemotherapy with HSCT rescue

Autologous HSCT within 100 days prior to first GEN3013 administration, or any prior allogeneic HSCT or solid organ transplantation

Active hepatitis B or ongoing hepatitis C infection that has not been cured. If laboratory evidence for a chronic infection with hepatitis B close monitoring and prophylactic therapy is required (see Section 6.6.1.3)

Known human immunodeficiency virus (HIV) infection

Exposed to live or live attenuated vaccine within 4 weeks prior to signing ICF

Pregnancy or breast feeding

Patient has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments

Contraindication to all uric acid lowering agents

Other exclusions may apply

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