Clinical trial NCT05451810: A Study to Evaluate Adverse Events of Subcutaneous (SC) Epcoritamab Administered in the Outpatient Setting in Adult Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma and Classic Follicular Lymphoma
Official title: A Phase 2, Open-Label Trial to Evaluate Safety of Epcoritamab Monotherapy in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma and Classic Follicular Lymphoma (Previously Grade 1-3a) When Administered in the Outpatient Setting
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Diffuse Large B-Cell Lymphoma
Classic Follicular Lymphoma
Keywords: Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Relapsed or Refractory Classic Follicular Lymphoma
Non-Hodgkins Lymphoma
Cancer
Epcoritamab
ABBV-GMAB-3013
EPCORE
Lead sponsor: Genmab
Sponsor class: INDUSTRY
Collaborators: name: AbbVie
First posted: 2022-07-11
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: B-cell Lymphoma is an aggressive and rare cancer of a type of immune cells (a white blood cell responsible for fighting infections). Classic Follicular Lymphoma is a slow-growing type of non-Hodgkin lymphoma. The purpose of this study is to assess the safety of epcoritamab in adult participants in relapsed or refractory (R/R) diffuse large b-cell lymphoma (DLBCL) who have received at least 1 prior line of systemic antilymphoma therapy including at least 1 anti-CD20 monoclonal antibody-containing therapy or R/R classic follicular lymphoma (cFL). Adverse events will be assessed.

Epcoritamab is an investigational drug being developed for the treatment of R/R DLBCL and R/R cFL. Study doctors will assess participants in a monotherapy treatment arm of epcoritamab. Participants will receive escalating doses of epcoritamab, until full dose is achieved. Approximately 184 adult participants with R/R DLBCL and R/R cFL will be enrolled in the study in approximately 80 sites in the United States of America.

Participants will receive escalating doses of subcutaneous epcoritamab, until full dose is achieved, in 28-day cycles.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.


Eligibility criteria: Inclusion Criteria:

* Life expectancy \>3 months on standard of care (SOC) treatment.
* Meets the following disease activity criteria:

  -- Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL):
  * Documented CD20+ mature B-cell neoplasm according to the the 5th edition of World Health Organization (WHO) classification of Haematolymphoid Tumours, based on most recent representative pathology report;
  * Diffuse large B-cell lymphoma, not otherwise specified (NOS) (de novo or transformed from follicular lymphoma (FL) or Marginal Zone Lymphoma \[MZL\]);
  * High-grade B-cell Lymphoma including "double-hit" or "triple-hit" DLBCL (technically classified in WHO 2022 or 2016 as high-grade B-cell lymphoma \[HGBCL\], with MYC and BCL2 and/or BCL6 translocations).
  * Follicular large B-cell lymphoma (FLBL, formerly FL grade 3B);
  * Relapsed or refractory disease and previously treated with at least 1 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 including but not limited to age, Eastern Cooperative Oncology Group (ECOG) performance status, participant decision, comorbidities and/or insufficient response to prior treatment.
* R/R Follicular Lymphoma:

  * Documented CD20+ mature B-cell neoplasm according to the 5th edition of WHO classification of Haematolymphoid Tumours, based on representative pathology report;

    --- Classic FL (cFL) (previously FL grade 1, 2, or 3a) without clinical or pathological evidence of transformation;
  * Relapsed or refractory disease and previously treated with at least 2 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.
* Has at least one target lesion defined as:

  * \>= 1 measurable nodal lesion (long axis \> 1.5 cm) and/or \>= 1 measurable extranodal lesion (long axis \> 1.0 cm) on CT (or MRI) AND
  * FDG PET scan demonstrating positive lesion(s) compatible with CT (or MRI) defined anatomical tumor sites.
* Must have ECOG performance status 0 - 2.
* Must have acceptable organ (renal, liver, and hematologic) function within the screening period prior to the first dose of study drug:

  * Absolute neutrophil count (ANC) \>= 1.0 × 10\^9/L (growth factor support allowed in case of bone marrow involvement, but participant must have not received growth factor within 14 days prior to screening lab collection);
  * Hemoglobin \>= 8.0 g/dL (RBC transfusions permitted, but participants must not have received blood transfusions within 7 days prior to Screening lab collection);
  * Platelet count \>= 75 × 10\^9/L, or \>= 50 × 10\^9/L in the presence of bone marrow involvement or splenomegaly (platelet transfusions are permitted, but participants must not have received blood transfusions within 7 days prior to Screening lab collection);
  * International normalized ratio (INR) (or Prothrombin Time \[PT\]) and 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); unless due to hepatic involvement of disease or non-hepatic origin. For participants with hepatic involvement of disease, serum AST and serum ALT \<= 5.0 × ULN
  * Direct bilirubin \<= 2 × ULN;
  * Estimated creatine clearance (CrCl) as calculated by Cockcroft-Gault Formula \>= 45 mL/min, or estimated glomerular filtration rate (eGFR) as calculated by Modification of Diet in Renal Disease \[MDRD\] equation \>= 45 mL/min;
  * Lymphocyte count \< 5 × 10\^9/L.

Exclusion Criteria:

* Have a primary central nervous system (CNS) lymphoma or known CNS involvement by lymphoma including leptomeningeal disease, at screening as confirmed by magnetic resonance imaging (MRI)/computed tomography (CT) scan (brain) and, if clinically indicated, by lumbar puncture.
* Uncontrolled Human Immunodeficiency Virus (HIV) infection. HIV viral load that is undetectable and controlled with medication for at least 1 year prior to enrollment is allowed. Note: If participant has no history of HIV infection, HIV testing does not need to be conducted at screening unless it is required per local guidelines or institutional standards.

Primary outcomes:
measure: Percentage of Participants Experiencing Grade 3 or Higher Cytokine Release Syndrome (CRS) Events
timeFrame: Up to 3 Months
measure: Percentage of Participants Experiencing Grade 3 or Higher Immune Cell-Associated Neurotoxicity Syndrome (ICANS) Events
timeFrame: Up to 3 Months
measure: Percentage of Participants Experiencing Grade 3 or Higher Neurotoxicity (Ntox) Events
timeFrame: Up to 3 Months
Secondary outcomes:
measure: Best Overall Response (BOR) Determined by Lugano 2014 Criteria Per Investigator Assessment
timeFrame: Up to 3 Months
measure: CR Determined by Lugano 2014 Criteria Per Investigator Assessment
timeFrame: Up to 3 Months
measure: Diversity Enriched Cohort: Incidence of Treatment-Emergent Adverse Events (TEAEs) by Severity Level
timeFrame: Up to 3 Months
measure: Diversity Enriched Cohort: Severity of TEAEs by Severity Level
timeFrame: Up to 3 Months
measure: Diversity Enriched Cohort: Incidence of Serious Adverse Events (SAEs) by Severity Level
timeFrame: Up to 3 Months
measure: Diversity Enriched Cohort: Severity of SAEs by Severity Level
timeFrame: Up to 3 Months
measure: Diversity Enriched Cohort: Median Time to Onset of CRS of Grade 3 or Higher
timeFrame: Up to 3 Months
measure: Diversity Enriched Cohort: Median Time to Resolution of CRS of Grade 3 or Higher
timeFrame: Up to 3 Months
measure: Diversity Enriched Cohort: Median Time to Onset of ICANS of Grade 3 or Higher
timeFrame: Up to 3 Months
measure: Diversity Enriched Cohort: Median Time to Resolution of ICANS of Grade 3 or Higher
timeFrame: Up to 3 Months
measure: Diversity Enriched Cohort: Median Time to Onset of Ntox of Grade 3 or Higher
timeFrame: Up to 3 Months
measure: Diversity Enriched Cohort: Median Time to Resolution of Ntox of Grade 3 or Higher
timeFrame: Up to 3 Months
measure: Diversity Enriched Cohort: Percentage of Participants Experiencing Any Adverse Events (AE)s
timeFrame: Up to 3 Months
measure: Diversity Enriched Cohort: Percentage of Participants Receiving Various Interventions for the Management of CRS After the First Full Dose of Epcoritamab
timeFrame: Up to 3 Months
measure: Diversity Enriched Cohort: Percentage of Participants Receiving Various Interventions for the Management of ICANS After the First Full Dose of Epcoritamab
timeFrame: Up to 3 Months
measure: Diversity Enriched Cohort: Percentage of Participants Receiving Various Interventions for the Management of Ntox After the First Full Dose of Epcoritamab
timeFrame: Up to 3 Months
measure: Diversity Enriched Cohort: Duration of response (DOR)
timeFrame: Up to 3 Months
measure: Diversity Enriched Cohort: Progression-free survival (PFS)
timeFrame: Up to 3 Months
measure: Diversity Enriched Cohort: Overall survival (OS)
timeFrame: Up to 3 Months
measure: Diversity Enriched Cohort: Time-to-response (TTR)
timeFrame: Up to 3 Months
measure: Diversity Enriched Cohort: Duration of CR (DOCR)
timeFrame: Up to 3 Months
measure: Diversity Enriched Cohort: Time to Next Treatment
timeFrame: Up to 3 Months
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Infirmary Health - Infirmary Cancer Care at Mobile Infirmary /ID# 264630
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences /ID# 244562
state: Arkansas
city: Springdale
country: United States
facility: Highlands Oncology Group, PA /ID# 245002
state: Arkansas
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center /ID# 255327
state: California
city: Fountain Valley
country: United States
facility: Compassionate Cancer Care Research Group - Fountain Valley /ID# 246133
state: California
city: Fresno
country: United States
facility: UCSF Fresno /ID# 263286
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles /ID# 244573
state: California
city: Boulder
country: United States
facility: Rocky Mountain Cancer Centers - Boulder /ID# 247653
state: Colorado
city: Stamford
country: United States
facility: Bennett Cancer Center - Stamford Hospital /ID# 244530
state: Connecticut
city: Washington
country: United States
facility: MedStar Washington Hospital Center /ID# 246068
state: District of Columbia
city: Jacksonville
country: United States
facility: Cancer Specialists of North Florida /ID# 261842
state: Florida
city: Lake Mary
country: United States
facility: Florida Cancer Specialists /ID# 260854
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center-Miami Beach /ID# 249045
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Hospital West /ID# 248432
state: Florida
city: Tamarac
country: United States
facility: BRCR Medical Center Inc /ID# 262527
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida /ID# 244532
state: Florida
city: Atlanta
country: United States
facility: Emory University, Winship Cancer Institute /ID# 246056
state: Georgia
city: Chicago
country: United States
facility: University of Illinois at Chicago /ID# 245038
state: Illinois
city: Niles
country: United States
facility: Illinois Cancer Specialists /ID# 247655
state: Illinois
city: Fort Wayne
country: United States
facility: Parkview Comprehensive Cancer Center /ID# 244545
state: Indiana
city: Indianapolis
country: United States
facility: Indiana Blood & Marrow Transpl /ID# 244971
state: Indiana
city: Des Moines
country: United States
facility: University of Iowa Health Care /ID# 258227
state: Iowa
city: Baton Rouge
country: United States
facility: Our Lady Of The Lake Regional Medical Center /ID# 255008
state: Louisiana
city: Bethesda
country: United States
facility: American Oncology Partners of Maryland /ID# 244968
state: Maryland
city: Columbia
country: United States
facility: Maryland Oncology Hematology /ID# 254192
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center /ID# 246074
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital /ID# 245239
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center /ID# 248651
state: Massachusetts
city: Grand Rapids
country: United States
facility: Cancer & Hematology Centers of Western Michigan - East /ID# 244985
state: Michigan
city: Ypsilanti
country: United States
facility: Trinity Health St. Joseph Mercy Ann Arbor /ID# 244547
state: Michigan
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic /ID# 244980
state: Mississippi
city: Chesterfield
country: United States
facility: St. Luke's Hospital - Chesterfield /ID# 247815
state: Missouri
city: Lincoln
country: United States
facility: NHO - Nebraska Hematology-Oncology /ID# 263164
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center - 1 Medical Center Drive /ID# 245003
state: New Hampshire
city: Hackensack
country: United States
facility: The John Theurer Cancer /ID# 262532
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center /ID# 244973
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico /ID# 252434
state: New Mexico
city: Bronx
country: United States
facility: New York Cancer and Blood Specialists - Bronx /ID# 264690
state: New York
city: New Hyde Park
country: United States
facility: New York Cancer & Blood Specialists - Lake Success Medical Oncology /ID# 264681
state: New York
city: New York
country: United States
facility: Stony Brook University Medical Center /ID# 244631
state: New York
city: New York
country: United States
facility: New York Cancer and Blood Specialists - New York /ID# 264676
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai /ID# 258610
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center-Koch Center /ID# 244628
state: New York
city: Port Jefferson Station
country: United States
facility: New York Cancer and Blood Specialists /ID# 259016
state: New York
city: Greenville
country: United States
facility: East Carolina University - Brody School of Medicine /ID# 248989
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Univ HS /ID# 245005
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc. /ID# 246182
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Arthur G.H. Bing, MD Cancer Center /ID# 260803
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic Cancer Center - Main /ID# 246852
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma, Stephenson Cancer Center /ID# 244568
state: Oklahoma
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center /ID# 246410
state: Oregon
city: Salem
country: United States
facility: Oregon Oncology Specialists in Salem /ID# 260570
state: Oregon
city: Allentown
country: United States
facility: Lehigh Valley Hospital-Cedar Crest /ID# 244984
state: Pennsylvania
city: Easton
country: United States
facility: Spoknwrd Clinical Trials /ID# 265232
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center /ID# 244979
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Ctr /ID# 244571
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital; McGlinn Cancer Institute /ID# 259181
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health /ID# 247654
state: South Carolina
city: Memphis
country: United States
facility: The West Clinic /ID# 245004
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center /ID# 260953
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - Austin Midtown /ID# 247656
state: Texas
city: Dallas
country: United States
facility: Texas Oncology-Presbyterian Cancer Center Dallas /ID# 262659
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Dallas - Worth Street /ID# 262956
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center /ID# 244552
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio Medical Center /ID# 247658
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Northeast Texas /ID# 247657
state: Texas
city: Gainesville
country: United States
facility: Virginia Cancer Specialists - Gainesville /ID# 248760
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates - Norfolk (Lake Wright) /ID# 265514
state: Virginia
city: Roanoke
country: United States
facility: Blue Ridge Cancer Center /ID# 260597
state: Virginia
city: Tacoma
country: United States
facility: Northwest Medical Specialties - Tacoma /ID# 245045
state: Washington
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials, LLC /ID# 254952
city: San Juan
country: Puerto Rico
facility: Auxilio Mutuo Cancer Center /ID# 254953
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: