NCT03283137

Combination of Pembrolizumab With TGR-1202 in Patients With Relapsed/Refractory CLL and B-cell NHL

A Phase I, Open-label, Dose-escalation Study to Assess the Safety, Tolerability and Efficacy of the Combination of Pembrolizumab With TGR-1202 in Patients With Relapsed/Refractory CLL and B-Cell Non-Hodgkin Lymphoma (NHL)

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: University of Chicago · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study will be a standard 3+3 design with a lead in of TGR-1202 at dose of 600mg (dose level 1) or 800mg daily (dose level 2) for 6 weeks, i.e. 2 cycles, followed by pembrolizumab at 200mg every 3 weeks for 8 cycles along with TGR-1202 for patients with relapsed/refractory B-cell NHL or CLL. If the dose of 600mg daily of TGR-1202 (dose level 1) is tolerated in the first cohort the dose will be increased to 800mg qd which is the only and final dose escalation. If TGR-1202 is not tolerated at 600mg daily the dose will be decreased to 400mg daily. The lead in of TGR-1202 was chosen to ensure clinical benefit and to minimize the occurrence of early overlapping toxicity with pembrolizumab as most toxicities were observed early on in the treatment with idelalisib, a related PI3K-inhibitor, and rituximab.

Detailed description

Of note, TGR-1202 has not been associated with treatment related pneumonitis, transaminitis, colitis, PCP-infection nor CMV-reactivation which distinguishes TGR-1202 from idelalisib's toxicity profile. Once the maximum tolerated dose has been safely reached the study will open an expansion cohort to enroll 18 patients with a patient group in which a clinical signal is detected. Another 7 patients (up to a total of 25 patients in the expansion cohort) may be enrolled after an interim analysis. The duration of therapy will be 2 cycles of TGR-1202 followed by 8 cycles with pembrolizumab and TGR-1202. Thereafter patient will continue on TGR-1202 at the MTD until disease progression. Subjects who experience disease progression while on TGR-1202 maintenance may be eligible for re-treatment with pembrolizumab for up to 6 cycles at the discretion of the Local Investigator if the patient experienced at least disease stabilization during the initial treatment with pembrolizumab, the subject meets the safety parameters listed in the inclusion/exclusion criteria, and the trial is still open. Subjects will resume therapy at the same dose and schedule at the time of initial discontinuation. If safety and feasibility of the combination is confirmed in this dose expansion cohort, a randomized phase II trial comparing TGR-1202 with pembrolizumab versus TGR-1202 could be considered in a larger patient population, possibly within the cooperative group setting for patients with relapsed/refractory B-cell NHL and CLL The primary objective of the dose expansion cohort will be CR rate. Secondary endpoints will include safety and feasibility, PFS, OS and clinical response (SD, PR, PD). Patients will be monitored for disease response, adverse events and survival for a minimum of 2 years following enrollment. During and after treatment, patients will be evaluated for toxicities, particularly immunologic adverse events including pneumonitis, autoimmune colitis, dermatitisetc. Peripheral blood, lymph node and bone marrow samples will be collected before and during the treatment course for the correlative studies outlined below. Complete blood counts and differential counts with a complete metabolic panel will be obtained at the time intervals. If the patients are confirmed to have disease progression or intolerable toxicities the patients will be offered alternative treatment at the physicians' discretion. All of the patients will be followed for survival. All patients will receive HSV prophylaxis with acyclovir 400mg po bid or per institutional standards.

Conditions

• CLL
• B-cell Non Hodgkin Lymphoma

Interventions

Type	Name	Description
DRUG	TGR-1202	TGR-1202 will be given at a dose of 600mg (dose level 1) or 800mg (dose level 2). If the dose of 600mg is tolerated in the first cohort, then the dose will be increased to 800mg which is the only and final dose escalation. If the dose of 600mg is not tolerated, then the dose will be decreased to 400mg daily.
DRUG	Pembrolizumab	Pembrolizumab will be given at 200 mg every 3 weeks. The dose will not be adjusted throughout the course of the study.

Timeline

• Start date: 2018-01-23
• Primary completion: 2027-12-01
• Completion: 2027-12-01
• First posted: 2017-09-14
• Last updated: 2025-02-07

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study