Study of TG-1701, an Irreversible Bruton's Tyrosine Kinase Inhibitor, in Patients With B-Cell Malignancies

Study Overview
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Brief Summary
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This is a Phase 1 trial to evaluate the safety, pharmacokinetics and efficacy of TG-1701, a Bruton's Tyrosine Kinase (BTK) inhibitor in patients with relapsed or refractory B-cell malignancies.

Detailed Description
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This Phase I clinical trial aims to evaluate the safety of the investigational drug TG-1701 both as a single-agent and in combination with other investigational drugs, specifically ublituximab and umbralisib. As per protocol v6.0, combination therapy (TG-1701 + Ublituximab + Umbralisib) will be discontinued and the participants from Arm 1 and 2 will be transitioned to the long-term extension period to receive TG-1701 monotherapy.

Official Title
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A Phase 1 Pharmacokinetic and Pharmacodynamic Study of TG-1701, an Irreversible Bruton's Tyrosine Kinase Inhibitor, in Patients With B-Cell Malignancies

Conditions
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Non Hodgkin Lymphoma, Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: TG-1701
* Drug: Umbralisib
* Biological: Ublituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsed or refractory histologically confirmed B-cell lymphoma or CLL Eastern Cooperative Oncology Group (ECOG) score of 0 to 2 Adequate organ function Exclusion Criteria: Prior therapy with a BTK inhibitor (ibrutinib, acalabrutinib, other) Any major surgery, chemotherapy or immunotherapy within the last 21 days Known hepatitis B virus, hepatitis C virus or HIV infection

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: TG-1701 Monotherapy<br>Participants will receive TG-1701 oral daily dose. As per protocol v6.0, participants from this arm will be transitioned to the long-term extension arm to receive TG-1701 monotherapy. | Drug: TG-1701<br>* Oral daily dose<br>|
| Experimental: Arm 2: TG-1701 + Ublituximab + Umbralisib<br>Participants will receive TG-1701, oral dose in combination with ublituximab, oral dose and umbralisib, fixed IV infusion on specific Days of Cycles 1 and 2, followed by maintenance infusions in Cycles 3 to 6 (Cycle=28 days). As per protocol v6.0, participants from this arm will be transitioned to the long-term extension arm to receive TG-1701 monotherapy. | Drug: TG-1701<br>* Oral daily dose<br>Drug: Umbralisib<br>* Oral Daily Dose<br>* Other names: TGR-1202;Biological: Ublituximab<br>* IV infusion<br>* Other names: TG-1101;|
| Experimental: Arm 3: Long Term Safety Extension - TG-1701 Monotherapy<br>All the ongoing participants from Arm 1 and 2, will be transitioned to TG-1701 monotherapy in long-term extension period, per protocol version 6.0. | Drug: TG-1701<br>* Oral daily dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose acceptable for participants | To determine the incidence of adverse events, any potential abnormal laboratory results and any dose-limiting toxicities. | From first dose up to 30 days post last dose (Up to approximately 4.8 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | To assess the overall response rate (ORR) in patients with hematologic malignancies | Up to approximately 4.8 years |