TG Therapeutics Announces Positive Data from Phase 3 GENUINE Trial of TG-1101 in Combination with Ibrutinib in Patients with High Risk Chronic Lymphocytic Leukemia at the 53rd Annual Meeting of the American Society of Clinical Oncology
Study met its primary endpoint with TG-1101 (ublituximab) plus ibrutinib increasing Overall Response Rate (ORR) by > 70% over ibrutinib alone
TG-1101 plus ibrutinib achieved 78% ORR, with 7% Complete Responses (CR), compared to 45% ORR with 0% CR's for Ibrutinib Alone, p < 0.001 (median follow-up 11.4 months), with all responses now confirmed as per iwCLL 2008 criteria
Combination of TG-1101 and ibrutinib resulted in 19% Minimal Residual Disease (MRD) negativity compared to 2% for Ibrutinib Alone, p < 0.01
A trend in improvement of PFS was observed with the combination of TG-1101 plus ibrutinib compared to ibrutinib alone (
The combination was well tolerated and TG-1101 did not appear to alter the safety profile of ibrutinib monotherapy, apart from infusion related reactions associated with TG-1101 which were primarily Grade 1/2
Highlight's from this presentation include the following:
Oral Presentation: Ublituximab and ibrutinib for previously treated genetically high-risk chronic lymphocytic leukemia: Results of the GENUINE Phase 3 study
This presentation includes data from the GENUINE Phase 3 trial, a multicenter, randomized trial (NCT02301156), which assessed the efficacy and safety of TG-1101 plus ibrutinib versus ibrutinib alone in patients with high risk CLL. For the trial, high-risk was defined as having any one or more of the following centrally confirmed features: 17p deletion, 11q deletion or p53 mutation. The GENUINE study was designed to demonstrate the value of adding TG-1101, a potent next generation glycoengineered anti-CD20 monoclonal antibody to ibrutinib monotherapy in high-risk CLL, and was powered to show a statistically significant improvement in ORR of 30%, with a minimal absolute detectable difference between the two arms of approximately 20%.
The trial met its primary endpoint, demonstrating a statistically significant improvement in Overall Response Rate (ORR), as assessed by blinded independent central radiology and hematology review by iwCLL (Hallek 2008) criteria, compared to ibrutinib alone in both the Intent to Treat (ITT) population (p=0.001) and Treated population (p < 0.001). Per iwCLL guidelines, all responders required confirmation of response for a minimum duration of 2 months. The ITT population includes all 126 randomized patients (64 in the TG-1101 plus ibrutinib arm and 62 in the ibrutinib alone arm) while the Treated population includes all ITT patients that received at least one dose of either study drug (59 in the TG-1101 plus ibrutinib arm and 58 in the ibrutinib alone arm).
One hundred and twenty-six (126) patients were randomized on the GENUINE Phase 3 trial. 100% of patients were high-risk and had either 17p deletion, 11q deletion or p53 mutation. Sixty-four percent (64%) of patients in the TG-1101 plus ibrutinib arm and 66% of patients in the Ibrutinib alone arm had 17p deletion and/or a p53 mutation while 36% and 34% of patients in the TG-1101 plus ibrutinib and ibrutinib alone arms, respectively, had an 11q deletion only. The median age of patients on either arm was 67 years and the median number of prior lines of therapy for either arm was 3.
Safety & Tolerability
One hundred and seventeen (117) patients were evaluable for safety (59 patients in the TG-1101 plus ibrutinib arm, and 58 patients in the ibrutinib alone arm). The combination was well tolerated and, apart from infusion related reactions, the addition of TG-1101 did not appear to alter the safety profile of ibrutinib monotherapy. Neutropenia, occurring in 9% of patients, was the most commonly reported Grade 3/4 Adverse Event (AE) in the combination arm, followed by infusion related reactions and anemia, each reported in 5% of patients. Notably, the majority of infusion related reactions (IRR) were Grade 1 or 2 in severity, with only 5% Grade 3/4 IRR observed. Median follow-up for this study was approximately 11.4 months.
|TG-1101 plus Ibrutinib||Ibrutinib||P-value|
|Treated Population (n)||n=59||n=58|
|Overall Response Rate (ORR)||78||%||45||%||P < 0.001|
|Complete Response (CR)||7||%||0||%||NS|
|P < 0.01|
|*Patients evaluable for MRD included those enrolled > 4 months prior to data cutoff date of |
In addition to the improvements in ORR, CR and MRD-negativity, a trend in improvement of Progression Free Survival (PFS) was observed in the combination
arm of TG-1101 plus ibrutinib as compared to ibrutinib alone (
ABOUT THE PHASE 3 GENUINE STUDY
The Phase 3 GENUINE study is a randomized, open label, multicenter clinical trial to evaluate the safety and efficacy of TG-1101 (ublituximab) plus ibrutinib compared to ibrutinib alone in adult patients with high-risk Chronic Lymphocytic Leukemia (CLL) who received at least one prior therapy for their disease.
The study was conducted at 160 clinical trial sites in the US and
The above referenced presentation is now available on the Publications page, located within the Pipeline section, of the Company's website at www.tgtherapeutics.com/publications.cfm.
TG THERAPEUTICS INVESTOR & ANALYST EVENT
Some of the statements included in this press release may be forward-looking statements that involve a number of risks and uncertainties. For those statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. In addition to the risk factors identified from time to time in our reports filed with the Securities and Exchange Commission, factors that could cause our actual results to differ materially are the following: the risk that early clinical trial results, that may have supported the acceptance of our data for presentation or influenced our decision to proceed with additional clinical trials, will not be reproduced in future studies; the risk that the
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Jenna BoscoVice President, Investor Relations TG Therapeutics, Inc.Telephone: 212.554.4351 Email: firstname.lastname@example.org
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