Epcoritamab for the Treatment of Relapsed or Refractory Post Transplant Lymphoproliferative Disorders

Registration Number
NCT06672705
Lead Sponsor
Timothy Voorhees
Brief Summary

This phase Ib trial tests the safety and effectiveness of epcoritamab in treating patients with post-transplant lymphoproliferative disorder (PTLD) that has come back after a period of improvement (relapsed) or has not responded to previous treatment (refractory). Epcoritamab, a bispecific antibody, binds to a protein called CD3, which is found on T cells (a...

Detailed Description

PRIMARY OBJECTIVE:

I. To assess the safety of treatment with epcoritamab in subjects with PTLD.

SECONDARY OBJECTIVES:

I. To estimate the Objective Response Rate (ORR), defined as the clinical response (complete response \[CR\] + partial response \[PR\]) after 3 cycles of epcoritamab.
...

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
26
Inclusion Criteria

  • Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information to the sponsor, sites, and relevant study organizations.

  • Age ≥ 18 years at the time of consent.

  • Karnofsky scale ≥ 50% or Eastern Cooperative Oncology Group (ECOG) ≤ 2.

  • Histological evidence of B-cell PTLD (any histologic subtype) following solid organ transplantation; expresses CD20; with or without EBV association.

  • Treatment failure of immunosuppression reduction (ISR). NOTE: if ISR was deemed not feasible by treating physician, ISR treatment failure may be waived.

  • Treatment failure of rituximab or rituximab plus any concurrent or sequentially administered chemotherapy regimen.

  • Measurable disease of > 1.5 cm in diameter and/or bone marrow involvement.

  • Subjects having undergone heart, lung, liver, kidney, pancreas, small intestine transplantation or a combination of the organ transplantations mentioned.

  • HIV infection is allowed if viral load is undetectable at time of enrollment, CD4+ count > 200 cells/uL, and subject remains on anti-viral therapy.

  • Resolution of toxicities from prior therapy to a grade that does not contraindicate trial participation in the opinion of the investigator.

  • Expected survival greater than 60 days.

  • Absolute neutrophil count 1.0 ≥ x 10^9/L.

  • Platelets 50 ≥ x 10^9/L.

  • Creatinine clearance (mL/min) ≥ 30 mL/min - Cockcroft-Gault Equation.

    • Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy.

  • Bilirubin ≤ 3.0 x upper limit of normal (ULN). Subjects with Gilbert's syndrome may be enrolled despite a total bilirubin level > 3.0 mg/dL if their conjugated bilirubin is ≤ 3.0 × ULN).

    • Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy.

  • Aspartate aminotransferase (AST) ≤ 3.0 x ULN.

    • Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy.

  • Alanine aminotransferase (ALT) ≤ 3.0 x ULN.

    • Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy.

  • Females of childbearing potential must have a negative serum pregnancy test within 3 days prior to registration. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided.

  • Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 12 months after treatment the last dose of epcoritamab. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device.

  • Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 12 months after the last dose of epcoritamab.

  • Subjects with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the experimental regimen are eligible for the trial.

  • Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee.

Read More
Exclusion Criteria
  • Uncontrolled active (symptomatic) infection. Patients requiring systemic therapy are eligible if the infection is deemed controlled by the investigator.
  • Post-transplant lymphoproliferative disorder following stem cell transplantation for hematologic malignancies or nonmalignant conditions.
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study and lactating females must agree to not breastfeed while taking study drug).
  • Subjects with central nervous system (CNS) involvement by PTLD.
  • Seizure disorder requiring therapy (such as steroids or anti-epileptics).
  • Uncontrolled concomitant illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association (NYHA) Class III or IV), unstable angina pectoris, myocardial infarction within 1 month prior to enrollment, uncontrolled cardiac arrhythmias, uncontrolled seizures, or severe non-compensated hypertension (systolic blood pressure > 180mmHg or diastolic blood pressure > 120mmHg).
  • History of progressive multifocal leukoencephalopathy.
  • Active Hepatitis B infection or Hepatitis C infection with positive viral polymerase chain reaction (PCR) from the blood. Subjects with active Hepatitis B infection and undetectable viral PCR from the blood will be allowed with concurrent use of entecavir suppression. Subjects with history of Hepatitis C infection (undetectable viral PCR) are allowed.
  • Electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant.
  • Any condition, including the presence of laboratory values which is deemed by the clinician to place the subject at an unacceptable risk or confounds the ability to interpret the data from this study.
  • Live virus vaccines must not be administered within 28 days of the start of study treatment.
  • Any investigational treatments must have been completed at least 4 weeks or 5 half-lives, whichever is shorter, prior to the start of study treatment. Investigational antibody therapies are not included in this requirement.
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment (epcoritamab)BiopsyPatients receive epcoritamab SC on days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 4-9, and day 1 of each subsequent cycle. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients with CR may continue to receive epcoritamab if disease progression occurs within 6 months. Patients with PR or SD continue to receive epcoritamab in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT and blood sample collection throughout the study and may undergo biopsy during screening.
Treatment (epcoritamab)Biospecimen CollectionPatients receive epcoritamab SC on days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 4-9, and day 1 of each subsequent cycle. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients with CR may continue to receive epcoritamab if disease progression occurs within 6 months. Patients with PR or SD continue to receive epcoritamab in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT and blood sample collection throughout the study and may undergo biopsy during screening.
Treatment (epcoritamab)Computed TomographyPatients receive epcoritamab SC on days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 4-9, and day 1 of each subsequent cycle. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients with CR may continue to receive epcoritamab if disease progression occurs within 6 months. Patients with PR or SD continue to receive epcoritamab in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT and blood sample collection throughout the study and may undergo biopsy during screening.
Treatment (epcoritamab)EpcoritamabPatients receive epcoritamab SC on days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 4-9, and day 1 of each subsequent cycle. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients with CR may continue to receive epcoritamab if disease progression occurs within 6 months. Patients with PR or SD continue to receive epcoritamab in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT and blood sample collection throughout the study and may undergo biopsy during screening.
Treatment (epcoritamab)Positron Emission TomographyPatients receive epcoritamab SC on days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 4-9, and day 1 of each subsequent cycle. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients with CR may continue to receive epcoritamab if disease progression occurs within 6 months. Patients with PR or SD continue to receive epcoritamab in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT and blood sample collection throughout the study and may undergo biopsy during screening.
Primary Outcome Measures
NameTimeMethod
Incidence of adverse eventsUp to 30 days after the last dose of the study drug

Will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) grading for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The dose limiting toxicity period will be the first ...

Secondary Outcome Measures
NameTimeMethod
Objective response rate (ORR)Up to completion of cycle 3 (1 cycle = 28 days)

Will be defined as the number of patients who achieve complete response (CR) + partial response (PR) divided by the number of evaluable patients, and presented with the 95% binomial confidence interval. Will be assessed using Lugano (with LYRIC modification) response criteria.

Clinical benefit rate (CBR)Up to 6 cycles (1 cycle = 28 days)

Will be defined as clinical response (CR + PR + stable disease) after 6 cycles of epcoritamab using Lugano (with LYRIC modification) response criteria. CBR rate will be estimated and 95% confidence interval computed.

Best ORRUp to 3 years

Will be defined as the number of patients who achieve best ORR (CR + PR) at any time after treatment with epcoritamab. Will be estimated with the 95% binomial confidence interval. Will be assessed using Lugano (with LYRIC modification) response criteria.

Progression free survivalFrom the date of treatment initiation to date of progression or death, whichever occurs first, assessed up to 3 years

Will be estimated using the Kaplan-Meier method. Will be assessed using the LYRIC response criteria.

Duration of complete responseFrom treatment response to date of progression or death, whichever occurs first, assessed up to 3 years

Will be estimated using the Kaplan-Meier method. Will be assessed using the LYRIC response criteria.

Overall survivalFrom date of treatment initiation to date of death due to all causes, assessed up to 3 years

Will be estimated using the Kaplan-Meier method.

Trial Locations

Locations (1)

Ohio State University Comprehensive Cancer Center

🇺🇸

Columbus, Ohio, United States

© Copyright 2024. All Rights Reserved by MedPath
HomeTerms & ConditionsPrivacy Policy