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

• ClinicalTrials.gov Identifier: NCT05451810
• Recruitment Status: Recruiting
• First Posted: July 11, 2022
• Last Update Posted: May 7, 2024
• Sponsor: Genmab
• Collaborator: AbbVie
• Information provided by (Responsible Party): Genmab

Tracking Information

• First Submitted Date: July 6, 2022
• First Posted Date: July 11, 2022
• Last Update Posted Date: May 7, 2024
• Actual Study Start Date: August 17, 2022
• Estimated Primary Completion Date: August 29, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 6, 2022)

• Percentage of Participants Experiencing Grade 3 or Higher Cytokine Release Syndrome (CRS) Events [ Time Frame: Up to 3 Months ]
  Cytokine Release Syndrome events will be graded using American Society for Transplantation and Cellular Therapy (ASTCT), with a higher grade indicating higher severity.
• Percentage of Participants Experiencing Grade 3 or Higher Immune Cell-Associated Neurotoxicity Syndrome (ICANS) Events [ Time Frame: Up to 3 Months ]
  ICANS events will be graded using ASTCT, with a higher grade indicating higher severity.
• Percentage of Participants Experiencing Grade 3 or Higher Neurotoxicity (Ntox) Events [ Time Frame: Up to 3 Months ]
  Ntox is defined as the percentage of participants who developed at least 1 Grade 3 or higher Ntox since the initiation of epcoritamab treatment.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 31, 2023)

• Best Overall Response (BOR) Determined by Lugano 2014 Criteria Per Investigator Assessment [ Time Frame: Up to 3 Months ]
  BOR is defined as the percentage of participants who achieved best overall response of complete response (CR) or partial response (PR) determined by Lugano 2014 criteria as assessed by investigators.
• CR Determined by Lugano 2014 Criteria Per Investigator Assessment [ Time Frame: Up to 3 Months ]
  Complete response is defined as the percentage of participants who achieved best overall response of CR determined by Lugano 2014 criteria as assessed by investigator.
• Diversity Enriched Cohort: Incidence of Treatment-Emergent Adverse Events (TEAEs) by Severity Level [ Time Frame: Up to 3 Months ]
  Treatment-emergent events (TEAEs) are defined as any event that began or worsened in severity after the first dose of study drug.
• Diversity Enriched Cohort: Severity of TEAEs by Severity Level [ Time Frame: Up to 3 Months ]
  Treatment-emergent events (TEAEs) are defined as any event that began or worsened in severity after the first dose of study drug.
• Diversity Enriched Cohort: Incidence of Serious Adverse Events (SAEs) by Severity Level [ Time Frame: Up to 3 Months ]
  A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.
• Diversity Enriched Cohort: Severity of SAEs by Severity Level [ Time Frame: Up to 3 Months ]
  A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.
• Diversity Enriched Cohort: Median Time to Onset of CRS of Grade 3 or Higher [ Time Frame: Up to 3 Months ]
  Median time to onset of CRS of Grade 3 or higher.
• Diversity Enriched Cohort: Median Time to Resolution of CRS of Grade 3 or Higher [ Time Frame: Up to 3 Months ]
  Median time to resolution of CRS of Grade 3 or higher.
• Diversity Enriched Cohort: Median Time to Onset of ICANS of Grade 3 or Higher [ Time Frame: Up to 3 Months ]
  Median time to onset of ICANS of Grade 3 or higher.
• Diversity Enriched Cohort: Median Time to Resolution of ICANS of Grade 3 or Higher [ Time Frame: Up to 3 Months ]
  Median time to resolution of ICANS of Grade 3 or higher.
• Diversity Enriched Cohort: Median Time to Onset of Ntox of Grade 3 or Higher [ Time Frame: Up to 3 Months ]
  Median time to onset of Ntox of Grade 3 or higher.
• Diversity Enriched Cohort: Median Time to Resolution of Ntox of Grade 3 or Higher [ Time Frame: Up to 3 Months ]
  Median time to resolution of Ntox of Grade 3 or higher.
• Diversity Enriched Cohort: Percentage of Participants Experiencing Any Adverse Events (AE)s [ Time Frame: Up to 3 Months ]
  An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
• Diversity Enriched Cohort: Percentage of Participants Receiving Various Interventions for the Management of CRS After the First Full Dose of Epcoritamab [ Time Frame: Up to 3 Months ]
  Percentage of participants receiving various interventions for the management of CRS after the first full dose of epcoritamab.
• Diversity Enriched Cohort: Percentage of Participants Receiving Various Interventions for the Management of ICANS After the First Full Dose of Epcoritamab [ Time Frame: Up to 3 Months ]
  Percentage of participants receiving various interventions for the management of ICANS after the first full dose of epcoritamab.
• Diversity Enriched Cohort: Percentage of Participants Receiving Various Interventions for the Management of Ntox After the First Full Dose of Epcoritamab [ Time Frame: Up to 3 Months ]
  Percentage of participants receiving various interventions for the management of Ntox after the first full dose of epcoritamab.
• Diversity Enriched Cohort: Duration of response (DOR) [ Time Frame: Up to 3 Months ]
  Duration of response is defined for participants who achieved BOR of CR or PR ('responders'), as the time in months from initial CR/PR to the earliest occurrence of disease progression determined by Lugano 2014 criteria as assessed by investigator, or death from any cause.
• Diversity Enriched Cohort: Progression-free survival (PFS) [ Time Frame: Up to 3 Months ]
  Progression-free survival is defined as the time in months from the first dose of study drug to the earliest occurrence of disease progression determined by Lugano 2014 criteria as assessed by investigator, or death from any cause.
• Diversity Enriched Cohort: Overall survival (OS) [ Time Frame: Up to 3 Months ]
  Overall survival is defined for as the time in months from first dose of epcoritamab to death from any cause.
• Diversity Enriched Cohort: Time-to-response (TTR) [ Time Frame: Up to 3 Months ]
  Time to response is defined for participants who achieved BOR of CR or PR ('responders') determined by Lugano 2014 criteria as assessed by investigator, as the time in months from first dose of study drug to initial CR/PR.
• Diversity Enriched Cohort: Duration of CR (DOCR) [ Time Frame: Up to 3 Months ]
  The duration of complete response is defined for participants who achieved BOR of CR (Complete Responders), as the duration from the first CR response to the earliest date of disease progression determined per Lugano 2014 criteria, as assessed by the investigator, or death, whichever occurs first.
• Diversity Enriched Cohort: Time to Next Treatment [ Time Frame: Up to 3 Months ]
  Time to next treatment is defined as the time from the date of the first dose of study drug to the start of new non-protocol-specified treatment or death from any cause.

Original Secondary Outcome Measures (submitted: July 6, 2022)

• Overall Response Rate (ORR) Determined by Lugano 2014 Criteria Per Investigator Assessment [ Time Frame: Up to 3 Months ]
  ORR is defined as the percentage of participants who achieved best overall response of complete response (CR) or partial response (PR) determined by Lugano 2014 criteria as assessed by investigators.
• CR Rate Determined by Lugano 2014 Criteria Per Investigator Assessment [ Time Frame: Up to 3 Months ]
  Complete response rate is defined as the percentage of participants who achieved best overall response of CR determined by Lugano 2014 criteria as assessed by investigator.
• Incidence of Treatment-Emergent Adverse Events (TEAEs) by Severity Level [ Time Frame: Up to 3 Months ]
  Treatment-emergent events (TEAEs) are defined as any event that began or worsened in severity after the first dose of study drug.
• Severity of TEAEs by Severity Level [ Time Frame: Up to 3 Months ]
  Treatment-emergent events (TEAEs) are defined as any event that began or worsened in severity after the first dose of study drug.
• Incidence of Serious Adverse Events (SAEs) by Severity Level [ Time Frame: Up to 3 Months ]
  A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.
• Severity of SAEs by Severity Level [ Time Frame: Up to 3 Months ]
  A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.
• Median Time to Onset of CRS of Grade 3 or Higher [ Time Frame: Up to 3 Months ]
  Median time to onset of CRS of Grade 3 or higher.
• Median Time to Resolution of CRS of Grade 3 or Higher [ Time Frame: Up to 3 Months ]
  Median time to resolution of CRS of Grade 3 or higher.
• Median Time to Onset of ICANS of Grade 3 or Higher [ Time Frame: Up to 3 Months ]
  Median time to onset of ICANS of Grade 3 or higher.
• Median Time to Resolution of ICANS of Grade 3 or Higher [ Time Frame: Up to 3 Months ]
  Median time to resolution of ICANS of Grade 3 or higher.
• Median Time to Onset of Ntox of Grade 3 or Higher [ Time Frame: Up to 3 Months ]
  Median time to onset of Ntox of Grade 3 or higher.
• Median Time to Resolution of Ntox of Grade 3 or Higher [ Time Frame: Up to 3 Months ]
  Median time to resolution of Ntox of Grade 3 or higher.
• Percentage of Participants Experiencing Any Adverse Events (AE)s [ Time Frame: Up to 3 Months ]
  An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
• Percentage of Participants Receiving Various Interventions for the Management of CRS After the First Full Dose of Epcoritamab [ Time Frame: Up to 3 Months ]
  Percentage of participants receiving various interventions for the management of CRS after the first full dose of epcoritamab.
• Percentage of Participants Receiving Various Interventions for the Management of ICANS After the First Full Dose of Epcoritamab [ Time Frame: Up to 3 Months ]
  Percentage of participants receiving various interventions for the management of ICANS after the first full dose of epcoritamab.
• Percentage of Participants Receiving Various Interventions for the Management of Ntox After the First Full Dose of Epcoritamab [ Time Frame: Up to 3 Months ]
  Percentage of participants receiving various interventions for the management of Ntox after the first full dose of epcoritamab.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Diffuse Large B-Cell Lymphoma
• Classic Follicular Lymphoma

Intervention

Drug: Epcoritamab

Subcutaneous Injection (SC)

Other Name: ABBV-GMAB-3013

Study Arms

• Experimental: Main Cohort: Epcoritamab Diffuse Large B-Cell Lymphoma (DLBCL)
  Participants with relapsed or refractory (R/R) DLBCL will receive subcutaneous (SC) epcoritamab in 28 day cycles.
  Intervention: Drug: Epcoritamab
• Experimental: Main Cohort: Epcoritamab Classic Follicular Lymphoma (cFL)
  Participants with R/R cFL will receive SC epcoritamab in 28 day cycles.
  Intervention: Drug: Epcoritamab
• Experimental: Diversity Enriched Cohort: Epcoritamab DLBCL
  Participants with R/R DLBCL will receive SC epcoritamab in 28 day cycles.
  Intervention: Drug: Epcoritamab
• Experimental: Diversity Enriched Cohort: Epcoritamab cFL
  Participants with R/R cFL will receive SC epcoritamab in 28 day cycles.
  Intervention: Drug: Epcoritamab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 31, 2023): 184
• Original Estimated Enrollment (submitted: July 6, 2022): 80
• Estimated Study Completion Date: May 1, 2029
• Estimated Primary Completion Date: August 29, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) or R/R Classic Follicular Lymphoma (cFL), with documented CD20+ mature B-cell neoplasm according to World Health Organization (WHO) classification 2016 or WHO classification 2008 based on representative and most recent pathology report:

  • Can include participants 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 1 prior systemic anti-lymphoma therapy for DLBCL and 2 prior systemic antineoplastic therapies for cFL including at least 1 anti-CD20 monoclonal antibody-containing therapy

• Has at least one target lesion defined as:

  • ≥ 1 measurable nodal lesion (long axis > 1.5 cm and short axis > 1.0 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 Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
• Adequate organ function.

Exclusion Criteria:

• Central nervous system (CNS) involvement by lymphoma.
• 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 subject 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: ABBVIE CALL CENTER; 844-663-3742; abbvieclinicaltrials@abbvie.com

• Listed Location Countries: Puerto Rico, United States

Administrative Information

• NCT Number: NCT05451810
• Other Study ID Numbers: M23-362
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• URL: https://vivli.org/ourmember/abbvie/

• Current Responsible Party: Genmab
• Original Responsible Party: AbbVie
• Current Study Sponsor: Genmab
• Original Study Sponsor: AbbVie
• Collaborators: AbbVie

Investigators

• Study Director: ABBVIE INC.; AbbVie

• PRS Account: Genmab
• Verification Date: May 2024