Extension Study of UTX-TGR-304
Research type
Research Study
Full title
A Multi-Center, Open-Label, Extension Study of Ublituximab (TG-1101) in Combination with TGR-1202 for Patients Previously Enrolled in Protocol UTX-TGR-304
IRAS ID
218251
Contact name
Ruth Pettengell
Contact email
Sponsor organisation
TG Therapeutics, Inc
Eudract number
2016-004339-19
Duration of Study in the UK
4 years, 0 months, 1 days
Research summary
Research Summary
Chronic Lymphocytic Leukemia (CLL) accounts for one third of all diagnosed cases of leukemia. Despite an array of available therapies, CLL remains an incurable disease. Furthermore, the presence of certain cytogenetic abnormalities and high-risk mutational features predicts for a reduced response to treatment resulting in a shorter period of progression-free survival. There is a pressing need for innovative, targeted therapies for the treatment of patients with CLL.
A Phase 3 randomized study (UTX-TGR-304) to assess the efficacy and safety of ublituximab in combination with TGR-1202 compared to obinutuzumab in combination with chlorambucil in patients with CLL was launched in September 2015. UTX-TGR-304 also compares ublituximab alone and TGR-1202 alone to the combination of ublituximab plus TGR-1202.
This companion study (UTX-TGR-204 ) is intended to provide the opportunity for patients who progress on UTX-TGR-304 Treatment Arms B (obinutuzumab plus chlorambucil), C (ublituximab), or D (TGR-1202) to receive the treatment combination (ublituximab plus TGR-1202). In addition at the time of UTX-TGR-304 study closure, this protocol will allow patients from Treatment Arm A (ublituximab plus TGR-1202) to continue combination therapy.Ublituximab is a glycoengineered monoclonal antibody that induces an immune response resulting in the lysis of B cells. TGR-1202 is a highly-specific, orally available phosphoinositide-3-kinase (PI3K) delta (δ) inhibitor with nanomolar inhibitory potency.
Given the non-overlapping mechanisms of action of each of these agents, the combination of ublituximab and TGR1202 was explored in a Phase I/Ib study in patients with previously treated hematologic malignancies (Lunning ASH 2014). The combination regimen is shown to be well tolerated with clinical activity noted in a variety of hematologic malignancies, with responses reported in patients with a broad range of non-Hodgkin’s lymphomas and CLL.
200 patients (15 patients in the UK) are anticipated to enroll in this companion study. The estimated duration of the study is 4 years.Summary of Results
This was a multi-center, open-label extension study for subjects previously enrolled in the parent study UTX-TGR-304. All subjects enrolled in this study (UTX-TGR-204) received U2 (Ublituximab+Umbralisib) until disease progression or until they were unable to continue treatment for any reason, such as lack of tolerability. A total of 119 subjects were enrolled, of which 116 subjects received at least 1 dose of study treatment and were included in the Safety Population.
The study was terminated by the sponsor and all subjects have discontinued treatment with the last patient visit occurring on 28 Jun 2022. The most common reason for treatment discontinuation was progressive disease (40.5% of subjects overall).
Overall, the median (range) age was 66.0 (45 to 87) years, 75.0% of subjects were males, 94.8% of subjects were White, and 58.6% of subjects were enrolled at sites in the US. More than half of the subjects (51.7%) were treatment naïve, and 48.3% were previously treated. The ECOG (According to Eastern Cooperative Oncology Group) performance status was 0 or 1 for 99.1% of the subjects. The median time since the most recent progression was 1.5 months, ranging from 0.2 to 23.1 months.
Overall, the median duration of exposure to ublituximab and umbralisib was 15.7 months and
14.6 months, respectively, and was lower (9.3 and 9.4 months, respectively) for subjects who rolled over from Arm C compared to subjects who rolled over from Arm B (20.3 and 22.3 months, respectively) or Arm D (10.7 and 11.7 months, respectively) in the parent study.
Overall, at least 1 treatment emergent adverse event (TEAE) was reported in 98.3% of subjects. The most common TEAEs (≥25% of subjects) were diarrhea (44.8%), nausea (37.9%), fatigue (31.9), neutropenia (26.7%), cough (25.9%), and IRR (25.0%). The most common TEAEs of Grade ≥3 was neutropenia, diarrhea, and pneumonia. TEAEs leading to death were reported in 11.2% of subjects driven by deaths due to COVID-19/COVID-19 pneumonia. Serious TEAEs in 49.1% of subjects, and 16.4% of subjects discontinued due to an adverse event.
In summary, treatment with U2 in subjects previously treated with obinutuzumab+chlorambucil, single-agent ublituximab, or single-agent umbralisib was well tolerated and exhibited a safety profile consistent with patients with hematologic malignancies treated with U2.REC name
London - Chelsea Research Ethics Committee
REC reference
17/LO/0272
Date of REC Opinion
4 May 2017
REC opinion
Further Information Favourable Opinion