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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03682796
• Other study ID #: TRPH-222-100
• Status: Completed
• Phase: Phase 1
• Start date: October 15, 2018
• Est. completion date: November 17, 2021

Study information

• Verified date: May 2022
• Source: Triphase Research and Development III Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: November 17, 2021
• Est. primary completion date: November 17, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• TRPH-222
administered by IV, 21-day Cycle

Locations

Country	Name	City	State
Canada	Jewish General Hospital	Montréal	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Banner MD Anderson	Gilbert	Arizona
United States	Sarah Cannon Research Institute at Tennessee Oncology	Nashville	Tennessee
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Triphase Research and Development III Corp.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)	To determine the MTD of TRPH-222	21 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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