Lymphoma, Lymphoma, B-Cell, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell, Lymphoma, Marginal Zone, Lymphoma, Non-Hodgkin
Conditions
Keywords
Antibody-Drug Conjugate, ADC, CD22, SMARTag™ technology, TRPH-222
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.
Interventions
DRUGTRPH-222
administered by IV, 21-day Cycle
Sponsors
Triphase Research and Development III Corp.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | 21 days | To determine the MTD of TRPH-222 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate incidence and severity of AEs, serious AEs, TRPH-222-related AEs, AEs leading to death or discontinuation from treatment | Up to 28 days after last dose of study drug | Safety |
| Tumor Activity | Up to 2 years | Assess tumor response - ORR for each NHL subtype using Lugano criteria, PFS from first dose to disease progression, OS from first dose to death, DOR for each NHL subtype assessed by Lugano |
| TRPH-222 Pharmacokinetics (PK) | 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 | Maximum concentration of TRPH-222 (Cmax), time to Cmax, Half-life (t 1/2), Exposure (area under the curve; AUC), Total body clearance (CL), Volume of distribution (Vd) |
| TRPH-222 anti-drug antibodies (ADA) | Prior to treatment, prior to C3D1 and every 3rd cycle thereafter, EOT60 | Assess the incidence of subjects who develop ADA to the ADC with TRPH-222 monotherapy |
Countries
Canada, United States
Outcome results
None listed