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

Sponsor

Triphase Research and Development III Corp. (Industry)

Overall Status

Completed

CT.gov ID

NCT03682796

Collaborator

(none)

Enrollment

Locations

Arms

37.1

Actual Duration (Months)

4.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma Lymphoma, B-Cell Lymphoma, Non-Hodgkin Lymphoma, Mantle-Cell Lymphoma, Marginal Zone Lymphoma, Large B-Cell, Diffuse Lymphoma, Follicular	Drug: TRPH-222	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

32 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 15, 2018

Actual Primary Completion Date :

Nov 17, 2021

Actual Study Completion Date :

Nov 17, 2021

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Escalation

Estimated to be <31 subjects across multiple centers

Drug: TRPH-222

administered by IV, 21-day Cycle

Experimental: Expansion

Estimated to be <121 subjects across multiple centers

Drug: TRPH-222

administered by IV, 21-day Cycle

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose (MTD) [21 days]
To determine the MTD of TRPH-222

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner MD Anderson	Gilbert	Arizona	United States	85234
2	Roswell Park Comprehensive Cancer Center	Buffalo	New York	United States	14263
3	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43219
4	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
5	Sarah Cannon Research Institute at Tennessee Oncology	Nashville	Tennessee	United States	37203
6	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2M9
7	Jewish General Hospital	Montréal	Quebec	Canada	H3T 1E2