Clinical trial NCT03682796: Study of TRPH-222 in Patients With Relapsed and/or Refractory B-Cell Lymphoma
Official title: Phase 1, Multicenter, Open-Label Study of the Antibody-Drug Conjugate TRPH-222 in Subjects With Relapsed and/or Refractory B-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Lymphoma, Mantle-Cell
Lymphoma, Marginal Zone
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Follicular
Keywords: Antibody-Drug Conjugate
ADC
CD22
SMARTag™ technology
TRPH-222
Lead sponsor: Triphase Research and Development III Corp.
Sponsor class: INDUSTRY
First posted: 2018-09-25
Enrollment: 32
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: This is a Phase 1, multi-center, open-label study of TRPH-222 monotherapy in subjects with relapsed and/or refractory B-cell NHL. The study will be conducted in two Stages: Dose-Escalation, Dose-Expansion.

Detailed description: In Dose Escalation, patients with DLBCL, FL (including transformed FL), MZL, and MCL were to be enrolled per dose cohort. In Dose Expansion, additional response-evaluable patients were to be enrolled in NHL subtype-specific cohorts including DLBCL and FL to confirm the RP2D identified in Escalation. Each stage consisted of screening, baseline, treatment, and follow-up periods. During the treatment period, patients were to be treated indefinitely in 21 day cycles. The EOT assessments were to occur 28 and 60 days after the last study treatment.

Eligibility criteria: Inclusion Criteria

* Age ≥ 18 years at the time of signing the informed consent
* Histologically confirmed (2016 WHO lymphoma classification) B-cell NHL that is DLBCL, FL (including transformed FL), MZL, or MCL
* Relapsed and/or refractory NHL requiring systemic therapy and have failed, are intolerant to, or are considered ineligible for standard of care anticancer treatments that are known to be potentially curative. Subjects must not be current candidates for HSCT. Participants who refuse standard treatments may also be considered provided that documentation is provided that the subject has been made aware of all therapeutic options
* Eastern Cooperative Oncology Group (ECOG) status 0-2

Exclusion Criteria

* Presence of a leukemic phase of the lymphoma
* "Double hit" or "triple hit" germinal center B cell lymphoma
* Previous solid organ allograft (except for corneal transplant)
* Peripheral neuropathy \> NCI-CTCAE Grade 1
* Significant organ dysfunction that would preclude study participation
* Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias
* Any other serious active disease or co-morbid medical condition, according to the Investigator's decision or Medical Monitor, that will substantially increase the risk associated with the subject's participation in the study

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: 21 days
Secondary outcomes:
measure: Evaluate incidence and severity of AEs, serious AEs, TRPH-222-related AEs, AEs leading to death or discontinuation from treatment
timeFrame: Up to 28 days after last dose of study drug
measure: Tumor Activity
timeFrame: Up to 2 years
measure: TRPH-222 Pharmacokinetics (PK)
timeFrame: Each Cycle is 21 days. Days 1, 8, 15 of Cycle 1; Day 1 of Cycle 2 and Cycle 3; Day 1 of every third cycle thereafter; up to Day 28 after last dose of study drug; Day 60 after last dose of study drug
measure: TRPH-222 anti-drug antibodies (ADA)
timeFrame: Prior to treatment, prior to C3D1 and every 3rd cycle thereafter, EOT60
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson
state: Arizona
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute at Tennessee Oncology
state: Tennessee
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montréal
country: Canada
facility: Jewish General Hospital
state: Quebec
Study officials:
affiliation: Roswell Park Cancer Institute
name: Francisco J Hernandez- Ilizaliturri, MD
role: PRINCIPAL_INVESTIGATOR
References: