Study of TRPH-222 in Patients With Relapsed and/or Refractory B-Cell Lymphoma

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase 1, Multicenter, Open-Label Study of the Antibody-Drug Conjugate TRPH-222 in Subjects With Relapsed and/or Refractory B-Cell Lymphoma

Conditions
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Lymphoma, Lymphoma, B-Cell, Lymphoma, Non-Hodgkin, Lymphoma, Mantle-Cell, Lymphoma, Marginal Zone, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular

Intervention / Treatment
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* Drug: TRPH-222


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Escalation<br>Estimated to be <31 subjects across multiple centers | Drug: TRPH-222<br>* administered by IV, 21-day Cycle<br>|
| Experimental: Expansion<br>Estimated to be <121 subjects across multiple centers | Drug: TRPH-222<br>* administered by IV, 21-day Cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) | To determine the MTD of TRPH-222 | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate incidence and severity of AEs, serious AEs, TRPH-222-related AEs, AEs leading to death or discontinuation from treatment | Safety | Up to 28 days after last dose of study drug | 
| Tumor Activity | 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 | Up to 2 years | 
| TRPH-222 Pharmacokinetics (PK) | 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) | 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 | 
| TRPH-222 anti-drug antibodies (ADA) | Assess the incidence of subjects who develop ADA to the ADC with TRPH-222 monotherapy | Prior to treatment, prior to C3D1 and every 3rd cycle thereafter, EOT60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibody-Drug Conjugate, ADC, CD22, SMARTag™ technology, TRPH-222