On September 20, 2021 TG Therapeutics, Inc. (NASDAQ: TGTX), reported data presentations at the XIX International Workshop on Chronic Lymphocytic Leukemia (iwCLL) (Press release, TG Therapeutics, SEP 20, 2021, View Source [SID1234587998]). Data highlights from each presentation are included below.
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The Company will also host a virtual investor and analyst event today, September 20, 2021 at 8:30 AM ET, to review the updated Phase 1 data evaluating the investigational combination of UKONIQ (umbralisib) and ublituximab (U2) plus venetoclax presented at iwCLL, as well as provide an overview of the ULTRA-V Phase 2/3 trial.
Michael S. Weiss, the Company’s Chairman and Chief Executive Officer, stated, "The iwCLL conference this past weekend was an exciting meeting, where we were able to share data from four combination trials, including updated data from our Phase 1/2 study of U2 plus venetoclax. Our goal has been to develop combination therapies utilizing U2 as a backbone and we believe the data presented this weekend showcase the breadth of the program, which includes combinations with targeted therapy as well as immunotherapy. With a March 25, 2022 PDUFA date in the US, we are excited about the potential approval of the U2 regimen for CLL patients and hope you all can join us this morning for our virtual event to review some of the encouraging data presented this past weekend."
IwCLL 2021 DATA HIGHLIGHTS
Oral Presentation Title: Umbralisib Plus Ublituximab (U2) Is Superior to Obinutuzumab Plus Chlorambucil (O+Chl) in Patients with Treatment-Naïve (TN) and Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL): Results from the Phase 3 UNITY-CLL Study
421 patients were randomized to the U2 (n=210) or O+Chl (n=211) arms; 57% of patients were treatment-naïve and 43% had relapsed/refractory (R/R) CLL
At a median follow-up of 36.7 months, U2 significantly prolonged independent review committee (IRC) assessed progression-free survival (PFS) vs O+Chl (median 31.9 months vs 17.9 months; hazard ratio 0.546 (p<0.0001))
PFS improvement with U2 vs O+Chl was consistent across all subgroups examined including treatment naïve patients (median 38.5 months vs 26.1 months, hazard ratio 0.482) and relapsed/refractory patients (median 19.5 months vs 12.9 months, hazard ratio 0.601)
Overall response rate (ORR) was significantly higher with U2 compared to O+Chl (83.3% vs 68.7%; p<0.001)
For the U2 arm, at a median treatment exposure of 21 months, most adverse events (AEs) were Grade 1 or 2 in severity and were relatively balanced between the treatment naïve and previously treated populations
Grade 3/4 Adverse Events (AEs) of clinical interest (U2 vs O+Chl) included elevated ALT (8.3% vs 1.0%), elevated AST (5.3% vs 2.0%), non-infectious colitis (1.9% vs 0%), infectious colitis (0.5% vs 0.5%), pneumonitis (0.5% vs 0%), rash (2.4% vs 0.5%), and opportunistic infections (5.8% vs. 1.5%)
Oral Presentation Title: A Phase 1/2 Study of Umbralisib, Ublituximab, and Venetoclax in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
Regimen was administered with 3 cycles of U2 as induction in cycles 1 through 3, U2 plus venetoclax in cycles 4, 5 and 6, followed by umbralisib plus venetoclax in cycles 7 through 12 in patients with relapsed or refractory (R/R) CLL. Patients with centrally confirmed undetectable minimal residual disease (uMRD) in the bone marrow after cycle 12 were permitted to stop all therapy, while MRD detectable patients continued on single agent umbralisib.
47 patients have now been treated as of the data cutoff with 57% of patients previously exposed to a BTK inhibitor
Best Overall Response Rate (ORR) was 100% amongst evaluable patients (n=46), including 37% complete response (CR) rate
At cycle 12, 91% of patients (n=34) achieved undetectable minimal residual disease (uMRD) in the peripheral blood (PB), and 72% of patients (n=32) achieved uMRD in the bone marrow (BM)
At a median follow up of 24.5 months, median progression-free survival has not been reached
Grade 3/4 adverse events (AEs) occurring in >5% of patients were neutropenia (28%), leukopenia (15%), lymphocytopenia (15%), infusion related reactions (9%), diarrhea (9%), and anemia (6%). No TLS events were observed during venetoclax administration
Oral Poster Presentation Title: TG-1701, a Selective Bruton Tyrosine Kinase (BTK) Inhibitor, as Monotherapy and in Combination with Ublituximab and Umbralisib (U2) in Patients with Chronic Lymphocytic Leukemia
A total of 50 patients with R/R CLL have been treated with TG-1701, with patients receiving monotherapy in the dose-escalation cohort (n=6), 200 mg in a dose-expansion cohort (n=20), 300 mg in a dose-expansion cohort (n=20), or TG-1701 in combination with U2 in the dose escalation cohort (n=4).
TG-1701 monotherapy was well tolerated and the maximum tolerated dose was not reached up to 400 mg QD.
Grade 3/4 AEs occurring in patients treated with 200 mg QD of TG-1701 (n=20), included neutropenia (10%), anemia (5%) and arthralgia (5%). Grade 3/4 AEs occurring in patients treated with 300 md QD of TG-1701 (n=20), included neutropenia (20%), COVID-19 (5%), ALT increased (5%) and AST increased (5%).
100% ORR observed in the 300 mg QD monotherapy expansion cohort at a median follow up of 12 months (n=19)
95% ORR observed in the 200 mg QD monotherapy expansion cohort at a median follow up of 19 months (n=20)
100% ORR observed in the 1701+U2 dose escalation (using doses of 100 mg to 300 mg QD of TG-1701) at a median follow up of 19 months (n=3)
Poster Presentation Title: Phase I/II Study of Umbralisib (TGR-1202), Ublituximab (TG-1101), and Pembrolizumab in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia and Richter’s Transformation: 5-Year Follow-up
A total of 20 patients with R/R CLL or Richter’s Transformation (RT) were treated with the triple combination of ublituximab, umbralisib, and pembrolizumab. Patients with CLL received 2 cycles of the U2 regimen before pembrolizumab was added for an additional 4 cycles, followed by umbralisib maintenance. Patients with RT received U2 + pembrolizumab for the first 4 cycles, followed by U2 maintenance. Twenty patients were evaluable for safety (11 CLL patients and 9 RT patients) and 19 were evaluable for efficacy (11 CLL and 8 RT).
The triple combination was well tolerated, with immune mediated toxicities not appearing above what would be expected with either umbralisib or pembrolizumab alone. Grade 3/4 AEs occurring in >20% of patients (n=20) include, neutropenia (45%), thrombocytopenia (15%), ALT increase (15%), leukopenia (10%), nausea (5%), fatigue (5%), and anemia (5%).
In this heavily pre-treated cohort with a median of 2 (1-9) prior lines of therapy:
— 91% ORR in patients with R/R CLL (n=11)
— 83% ORR in BTK refractory CLL patients (n=6), with 4 of 5 responders achieving a response to U2 alone at the patient’s first efficacy assessment, prior to the addition of pembrolizumab
— 25% ORR in patients with RT (n=8), including 25% CR rate
The above data presentations are available on the Publications page, located within the Pipeline section, of the Company’s website at www.tgtherapeutics.com/publications.cfm.
INVESTOR & ANALYST VIRTUAL EVENT INFORMATION
The Company will host a virtual event today, September 20, 2021 at 8:30 AM ET, to discuss the updated Phase 1 data evaluating UKONIQ (umbralisib) and ublituximab (U2) in combination with venetoclax in patients with CLL as well as provide an overview of the Phase 2/3 ULTRA-V program.
To attend the live event, please visit the Events page, located within the Investors & Media section, of the Company’s website at View Source Following the live event, an archive file will be available for replay, for a period of 30 days after the call.
ABOUT U2 PLUS VENETOCLAX PHASE 1 TRIAL
The Phase 1/2 trial, (NCT03379051), is a multi-center, dose-escalation trial designed to assess the safety and efficacy of UKONIQ and ublituximab (U2) plus venetoclax in patients with relapsed or refractory CLL. The primary objective of the trial is to evaluate the safety of venetoclax after U2 induction. The secondary objectives are clinical efficacy as defined by overall response rate (ORR), including complete response (CR) rate, progression-free survival (PFS), and undetectable minimal residual disease (uMRD) rate after 12 cycles of therapy. The trial enrolled approximately 50 CLL patients and is being led by Dr. Paul Barr of the Wilmot Cancer Institute, University of Rochester Medical Center.
ABOUT ULTRA-V PHASE 2 TRIAL
The ULTRA-V Phase 2 trial, (NCT03801525), is an open-label, multicenter, trial designed to investigate the efficacy and safety of UKONIQ and ublituximab (U2) combined with venetoclax in subjects with CLL. The primary endpoint of the trial is overall response rate (ORR) and complete response (CR) rate. The trial enrolled approximately 165 patients with front-line and previously treated CLL at 26 sites throughout the United States.
ABOUT ULTRA-V PHASE 3 TRIAL
The ULTRA-V Phase 3 trial is an open-label, multicenter, randomized controlled clinical trial comparing the time-limited triple combination of UKONIQ and ublituximab (U2) plus venetoclax, to an active control arm of continuous U2. The Phase 3 trial includes two independent randomized cohorts of CLL subjects: a treatment-naïve cohort and a previously treated cohort, with each cohort being enrolled and evaluated independently of each other. The primary endpoint for the trial is progression-free survival (PFS). This trial is being led by Richard R. Furman, MD, Director of CLL Research Center at Weill Cornell Medicine and targeting over 60 U.S. trial sites.