On June 5, 2017 Novartis reported a first-of-its-kind collaboration with IBM Watson Health on an initiative to optimize cancer care and improve patient outcomes (Press release, Novartis, JUN 5, 2017, View Source [SID1234519453]). The two companies will collaborate to explore development of a cognitive solution that uses real-world data and advanced analytical techniques with the aim to provide better insights on the expected outcomes of breast cancer treatment options.

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With one of the broadest portfolios and largest number of advanced breast cancer compounds in development, breast cancer is a priority oncology focus area for Novartis. Scientific understanding of advanced breast cancer is improving and the treatment landscape is expanding, but new therapies and real-world evidence can raise more questions around the optimal treatment plan for individual patients.

This collaboration will join Novartis expertise in breast cancer with IBM Watson Health skill in data analytics and machine learning to determine which combinations and sequences may lead to the best patient outcomes. The initiative primarily will use real-world patient data.

"Through this collaboration with IBM Watson Health, we will use real-world breast cancer data and cognitive computing to identify solutions that may help physicians better understand which therapy may be best for which patients or advise clinical practice guidelines, with the goal of improving patient outcomes and experiences," said Bruno Strigini, CEO, Novartis Oncology. "We hope this collaboration also uncovers care efficiencies that can be applied beyond breast cancer."

"At Watson Health, we are tackling some of the world’s greatest challenges at the nexus of science and data, and we are proud to work with Novartis to better individualize advanced breast cancer treatment approaches in an effort to enhance patient care," said Anil Jain, MD, chief medical informatics officer, IBM Watson Health. "As the industry shifts toward value-based care, it’s critical for clinicians to understand the real-world outcomes of therapeutics on subsets of their patients, and our goal ultimately is to put those insights into oncologists’ hands. With the deep expertise of Novartis in breast cancer, we are confident that this collaboration may provide transformative tools for clinicians and patients to make more informed treatment decisions."

Watson is the first commercially available cognitive computing capability representing a new era in computing. The system, delivered through the cloud, analyzes high volumes of data, understands complex questions posed in natural language and proposes evidence-based answers. Watson continuously learns, gaining in value and knowledge over time, from previous interactions.

For more than 25 years, Novartis has been at the forefront of driving scientific advancements for breast cancer patients. Novartis has four marketed products in breast cancer: Kisqali* (ribociclib), Afinitor (everolimus), Tykerb/Tyverb (lapatinib) and Femara (letrozole). Novartis also has the largest number of breast cancer compounds in development, including BYL719 (alpelisib), an alpha-specific PI3K inhibitor; LSZ102, an oral SERD; LJM716, a fully human, anti-HER3 IgG1 antibody; and MCS110, a colony-stimulating factor 1 (CSF1) inhibitor.

*Kisqali is only commercially available in the United States.

On June 5, 2017 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new immunotherapies, reported updated results from its Phase 1 multicenter study of Ad-RTS-hIL-12 + veledimex including the 20 mg expansion cohort in patients with recurrent or progressive glioblastoma (GBM) at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting June 2-6 in Chicago (Press release, Ziopharm, JUN 5, 2017, View Source [SID1234519448]).

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In a poster presentation titled "Expanded phase I study of intratumoral Ad-RTS-hIL-12 + oral veledimex: tolerability and survival in recurrent glioblastoma," the Company reported results from 25 patients with recurrent or progressive Grade III or IV glioma enrolled in three veledimex dosing cohorts (20 mg, n = 15; 30 mg, n = 4; and 40 mg, n = 6). Subjects with recurrent or progressive Grade III or IV glioma undergoing resection were injected intratumorally with Ad 2 x 1011 viral particles and received daily oral activator veledimex for 15 doses.

As of May 24, 2017, the cutoff date for the ASCO (Free ASCO Whitepaper) presentation, median overall survival (mOS) of all patients receiving intratumoral Ad-RTS-hIL-12 with 20 mg of orally-administered veledimex was maintained at 12.5 months, with a mean follow-up time of 9.2 months. The majority of patients in the 20 mg cohort had 2 or more recurrences prior to entry in the study, indicating very advanced disease.

"With the ability to control and turn IL-12 expression on and off from within the brain tumor, Ad-RTS-hIL-12 + veledimex offers the potential to safely direct one of the most potent anti-cancer immune cytokines against one of the most aggressive and lethal cancers," said E. Antonio Chiocca, MD, PhD, Harvey W. Cushing Professor of Neurosurgery, Department of Surgery, Harvard Medical School, Surgical Director, Center for Neuro-oncology, Dana-Farber Cancer Institute, Chairman, Neurosurgery, Brigham and Women’s Hospital and Co-Director, Institute for the Neurosciences, Brigham and Women’s Hospital.

Dr. Chiocca added, "These data suggest that intra-tumor expression of IL-12 is well tolerated by patients with recurrent glioblastoma. There are also highly encouraging observations that activation of the immune system in the patients may result in anti-tumor effects. I look forward to understanding Ad-RTS-IL-12 + veledimex’s full potential in this challenging disease in a larger study."

Based on the ratio of CD8+/FOXP3+ (effector/suppressor) T cells measured in peripheral blood 14 to 28 days after viral injection, survival appears correlated with IL-12-mediated cellular immune activation. Consistent with this observation, steroid use in the first 15 days after injection of the virus appears to have a deleterious effect on patient survival, presumably due to interference with immune activation. Drug-related toxicities, which were primarily non-neurologic, showed a dose response to veledimex, were consistent with those previously reported, and importantly, continue to be reversed upon cessation of the activator ligand, with no drug-related deaths. As previously reported, a strong, dose-dependent correlation between veledimex dose, veledimex blood brain barrier penetration, IL-12 and IFN-gamma production was also observed.

"We are now seeing a correlation between survival and cellular immune modulation, in addition to maintenance of the survival benefit in the expanded 20 mg veledimex dose cohort," said Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM. "We have uncovered that the effects of an IL-12-driven immune activation is dampened by the concurrent use of high-dose steroids. This is reflected in the survival of the patients, where patients who received less than 10 mg of dexamethasone have a much better survival than those on elevated systemic steroids. We are excited about Ad-RTS-hIL-12 + veledimex moving into a pivotal study this year, following completion of our discussions with regulators."

A copy of the poster presentation is available at www.ziopharm.com.

Details for the poster presentation at ASCO (Free ASCO Whitepaper) 2017:

Title: Expanded phase I study of intratumoral Ad-RTS-hIL-12 + oral veledimex: tolerability and survival in recurrent glioblastoma
Abstract Number: 2044
Session: Central Nervous System Tumors
Date and Time: Monday, June 5, 2017, 1:15 — 4:45 p.m. CT

Ad-RTS-hIL-12 + veledimex

Ad-RTS-hIL-12 + veledimex is a novel, viral gene therapy candidate for the controlled expression of interleukin-12 (IL-12), a pro-inflammatory cytokine critical for stimulating anti-cancer immune responses.

Recurrent Glioblastoma (GBM)

Glioblastoma represents approximately 15% of all primary brain tumors and remains a high unmet clinical need that affects roughly 74,000 people worldwide annually.i,ii GBM is an aggressive form of brain cancer with recurrence rates near 90%, and prognosis for patients is poor with treatment often combining multiple approaches including surgery, radiation, and chemotherapy. Patients with recurrent GBM typically have a mOS of 6-7 months, and overall survival in patients who have failed temozolomide, bevacizumab or equivalent salvage chemotherapy, is approximately 3-5 months.iii,iv

On June 5, 2017 Abbvie IMBRUVICA (ibrutinib) reduced cells that may play an important role in the survival and proliferation of chronic lymphocytic leukemia (CLL), without negatively impacting non-cancerous immune system cells, through one year of treatment, according to new data presented today at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago (poster session: 8:00 a.m. – 11:30 a.m. CDT; abstract #7524).1 The data regarding IMBRUVICA, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, were announced by AbbVie (NYSE: ABBV), a global biopharmaceutical company. IMBRUVICA is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

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The data, which assessed the impact of treatment on the immune system and changes in circulating cells, found that IMBRUVICA reduced cancerous cells and other cells of the immunosuppressive tumor microenvironment including CLL cells (90 percent), myeloid-derived suppressor cells (MDSC, 61 percent) and some T cells (27-52 percent). At the same time, IMBRUVICA spared non-cancerous immune system cells, including naïve T cells, T memory stem cells (TSCM) and natural killer (NK) cells through one year of treatment. Classical monocytes (a type of white blood cell) were increased by 187 percent, while non-classical monocytes and intermediate monocytes remained relatively steady. The data were derived from the Phase 3 RESONATE-2 trial (PCYC-1115), which found IMBRUVICA reduced the risk of progression or death of treatment-naïve patients with CLL compared to the traditional chemotherapeutic chlorambucil.1

"These results show the IMBRUVICA mechanism of action at work and provide greater clarity on the potential role that BTK inhibition plays in tumor modulation," said Danelle James, M.D., M.S., Head of Clinical Science, Pharmacyclics LLC, an AbbVie company. "These data suggest that treatment with the chemotherapy agent chlorambucil has broad effects when administered to CLL patients – where almost all subsets of normal immune cells are impacted or decreased. In contrast, treatment with ibrutinib resulted in preservation of certain important immune cell subsets, providing evidence that IMBRUVICA may offer a more targeted treatment approach."

The study found treatment with chlorambucil indiscriminately affected most immune cell subsets in circulation, including progressively reducing circulating B, T, NK, NKT cells, MDSC and monocytes by 69-99 percent. All development stages of CD4+ and CD8+ T cells, except TSCM, decreased by 51-90 percent. Regulatory T cells (Treg) and PD1+ T cells also decreased similarly; however, long-term activated T cells (TLA) were not impacted.1

"We’ve made substantial progress in cancer treatment over the years with the discovery and introduction of novel therapies such as IMBRUVICA. We are able to more specifically target the tumor while sparing normal immune cells, and the study data show the potential for improved treatment options that eliminate or minimize the use of chemotherapy in CLL," added James.

CLL is a type of cancer that starts from cells that become certain white blood cells (called lymphocytes) in the bone marrow. The leukemia (cancer) cells start in the bone marrow but then spread into the blood. There are more than 20,000 newly diagnosed CLL patients every year.2 CLL is primarily a disease of the elderly, with a median age of 71 at diagnosis.3 To date, more than 25,000 CLL patients have been treated in the U.S. with IMBRUVICA since approval in 2014.

In the study over one year, immunophenotypic analyses were performed by flow cytometry on peripheral blood to assess lymphoid and myeloid cells of treatment-native CLL patients who received IMBRUVICA 420 mg once daily (n=50) or 0.5-0.8 mg/kg chlorambucil twice a month (n=30).1

About the RESONATE-2 Study

RESONATE-2 is a Pharmacyclics-sponsored, randomized, multi-center, open-label, Phase 3 study which enrolled 269 treatment-naïve patients with CLL/small lymphocytic leukemia (SLL) aged 65 years or older in the U.S., EU and other regions. Patients were randomized to receive either IMBRUVICA 420 mg orally, once daily until progression or unacceptable toxicity, or chlorambucil on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in Cycle 1 was 0.5 mg/kg and was increased based on tolerability in Cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg. The study met its primary endpoint, demonstrating improved progression free survival (PFS), as assessed by an independent review committee (IRC).

The most common adverse events (AEs >20%) of all Grades in the RESONATE-2 trial for ibrutinib were diarrhea (42%), fatigue (30%), cough (22%) and nausea (22%); AEs for chlorambucil included nausea (39%), fatigue (38%), neutropenia (23%) and vomiting (20%). Hypertension occurred at a higher rate with ibrutinib (14%), including Grade 3 (4%) with no Grade 4 or 5 events. All six patients with Grade 3 hypertension were managed with hypertensive medication and did not require ibrutinib dose reduction or discontinuation. Atrial fibrillation occurred in eight patients (6%) in the ibrutinib arm and was primarily Grade 2 in six patients and Grade 3 in two patients. It was managed with discontinuation in two patients and without a dose modification in remaining patients.

Overall, AEs leading to treatment discontinuation were less frequent with ibrutinib than with chlorambucil (9% versus 23%). There were three deaths in the ibrutinib arm and 17 deaths in the chlorambucil arm over the median follow-up of 18.4 months. None of the patients who progressed on ibrutinib died during the subsequent follow-up period.

About IMBRUVICA
IMBRUVICA (ibrutinib) is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton’s tyrosine kinase (BTK). BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells.3,4 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.4

IMBRUVICA is FDA-approved in five distinct patient populations: CLL, SLL, Waldenström’s macroglobulinemia (WM), along with previously-treated mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL).4

IMBRUVICA was first approved for patients with MCL who have received at least one prior therapy in November 2013.
Soon after, IMBRUVICA was initially approved in CLL patients who have received at least one prior therapy in February 2014. By July 2014, the therapy received approval for CLL patients with 17p deletion, and by March 2016, the therapy was approved as a frontline CLL treatment.
IMBRUVICA was approved for patients with WM in January 2015.
In May 2016, IMBRUVICA was approved in combination with bendamustine and rituximab (BR) for CLL/SLL patients.
In January 2017, IMBRUVICA was approved for patients with MZL who require systemic therapy and have received at least one prior anti-CD20-based therapy.
Accelerated approval was granted for the MCL and MZL indications based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.4

IMBRUVICA was one of the first medicines to receive U.S. FDA approval via the new Breakthrough Therapy Designation pathway. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases. IMBRUVICA has been granted four Breakthrough Therapy Designations from the FDA, spanning CLL/SLL, WM, MCL, and chronic graft-versus-host-disease (cGVHD). In addition, IMBRUVICA is the first standard therapy specifically approved for patients with previously-treated MZL and WM.

IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA has one of the most robust clinical oncology development programs for a single molecule in the industry, with approximately 130 ongoing clinical trials. There are a total of 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and approximately 100 investigator-sponsored trials and external collaborations that are active around the world. To date, 70,000 patients around the world have been treated with IMBRUVICA in clinical practice and clinical trials.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage – Fatal bleeding events have occurred in patients treated with IMBRUVICA. Grade 3 or higher bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA.

The mechanism for the bleeding events is not well understood. IMBRUVICA may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding. Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre- and postsurgery depending upon the type of surgery and the risk of bleeding.

Infections – Fatal and nonfatal infections have occurred with IMBRUVICA therapy. Grade 3 or greater infections occurred in 14% to 29% of patients. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA. Evaluate patients for fever and infections and treat appropriately.

Cytopenias – Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 13% to 29%), thrombocytopenia (range, 5% to 17%), and anemia (range, 0% to 13%) based on laboratory measurements occurred in patients treated with single agent IMBRUVICA. Monitor complete blood counts monthly.

Atrial Fibrillation – Atrial fibrillation and atrial flutter (range, 6% to 9%) have occurred in patients treated with IMBRUVICA, particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of atrial fibrillation. Periodically monitor patients clinically for atrial fibrillation. Patients who develop arrhythmic symptoms (eg, palpitations, lightheadedness) or new-onset dyspnea should have an ECG performed. Atrial fibrillation should be managed appropriately and if it persists, consider the risks and benefits of IMBRUVICA treatment and follow dose modification guidelines.

Hypertension – Hypertension (range, 6% to 17%) has occurred in patients treated with IMBRUVICA with a median time to onset of 4.6 months (range, 0.03 to 22 months). Monitor patients for new-onset hypertension or hypertension that is not adequately controlled after starting IMBRUVICA. Adjust existing antihypertensive medications and/or initiate antihypertensive treatment as appropriate.

Second Primary Malignancies – Other malignancies (range, 3% to 16%) including non-skin carcinomas (range, 1% to 4%) have occurred in patients treated with IMBRUVICA. The most frequent second primary malignancy was non-melanoma skin cancer (range, 2% to 13%).

Tumor Lysis Syndrome – Tumor lysis syndrome has been infrequently reported with IMBRUVICA therapy. Assess the baseline risk (eg, high tumor burden) and take appropriate precautions. Monitor patients closely and treat as appropriate.

Embryo-Fetal Toxicity – Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Advise men to avoid fathering a child during the same time period.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were neutropenia** (61%), thrombocytopenia** (62%), diarrhea (43%), anemia** (41%), musculoskeletal pain (30%), rash (30%), nausea (29%), bruising (30%), fatigue (29%), hemorrhage (22%), and pyrexia (21%).

** Based on adverse reactions and/or laboratory measurements (noted as platelets, neutrophils, or hemoglobin decreased).

The most common Grade 3 or 4 non-hematologic adverse reactions (≥5%) in MCL patients were pneumonia (7%), abdominal pain (5%), atrial fibrillation (5%), diarrhea (5%), fatigue (5%), and skin infections (5%).

The most common Grade 3 or 4 non-hematologic adverse reactions (≥5%) in MZL patients were pneumonia (10%), fatigue (6%), diarrhea (5%), rash (5%), and hypertension (5%).

Approximately 6% (CLL/SLL), 14% (MCL), 11% (WM) and 10% (MZL) of patients had a dose reduction due to adverse reactions. Approximately 4%-10% (CLL/SLL), 9% (MCL), and 9% (WM [6%] and MZL [13%]) of patients discontinued due to adverse reactions. Most common adverse reactions leading to discontinuation were pneumonia, hemorrhage, atrial fibrillation, rash, and neutropenia (1% each) in CLL/SLL patients and subdural hematoma (1.8%) in MCL patients. The most common adverse reactions leading to discontinuation were interstitial lung disease, diarrhea, and rash (1.6% each) in WM and MZL patients.

DRUG INTERACTIONS

CYP3A Inhibitors – Avoid coadministration with strong and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA dose.

CYP3A Inducers – Avoid coadministration with strong CYP3A inducers.

SPECIFIC POPULATIONS

Hepatic Impairment – Avoid use in patients with moderate or severe baseline hepatic impairment. In patients with mild impairment, reduce IMBRUVICA dose.

Please see Full Prescribing Information: View Source

June 05, 2017 (GLOBE NEWSWIRE) — TG Therapeutics, Inc. (NASDAQ:TGTX), reported updated clinical data from its ongoing Phase I/Ib trial of TG-1101 (ublituximab), the Company’s novel glycoengineered anti-CD20 monoclonal antibody in combination with TGR-1202 (umbralisib), the Company’s oral, next generation PI3K delta inhibitor, and ibrutinib, a BTK inhibitor, in patients with Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin’s Lymphoma (NHL). Data from this trial was presented today during the 53rd American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL. Additionally, a poster was presented describing the design of a study evaluating TGR-1202 in CLL patients who are intolerant to prior kinase inhibitor (KI) therapy, particularly ibrutinib and idelalisib.

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer stated, "The triple data presented today provides a compelling case for combining our doublet, referred to as TG-1303, with ibrutinib across a number of b-cell malignancies for which ibrutinib is now approved. Importantly, the high rates of complete responses observed across these diseases with the triple therapy may enable some patients to discontinue treatment prior to becoming ibrutinib refractory, a population associated with very poor outcomes." Mr. Weiss continued, "Additionally, the data shown today strengthens our belief that TG-1303 is a safe and efficacious backbone upon which we can build triple and quad therapies, as we continue to strive towards identifying combinations that provide deeper remissions that can ideally avoid lifetime treatment. We look forward to further exploring multi-drug combination therapies both with currently approved agents as well as with our in-house pipeline products."

Highlights from today’s presentations include the following:

Poster Presentation: Tolerability and activity of chemo-free triplet combination of TGR-1202, ublituximab, and ibrutinib in patients with advanced CLL and NHL (Abstract #7511)

Poster Viewing & Discussion Details: Monday, June 5, 2017 8:00 AM-11:30 AM CT (Poster Viewing); 1:15 PM-2:30 PM CT (Poster Discussion)

This poster presentation includes data from patients with Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) and Non-Hodgkin’s Lymphoma (NHL) treated with the triple combination of TGR-1202, TG-1101 and ibrutinib. All patients were relapsed or refractory to prior therapy, except 3 CLL patients who were treatment naïve. Three cohorts for each CLL/SLL and NHL were evaluated with TGR-1202 dose escalation starting with doses of 400 mg (cohort 1), followed by 600 mg (cohort 2) and 800 mg (cohort 3), in combination with TG-1101 at 900 mg and ibrutinib daily at 420 mg (CLL) and 560 mg (NHL).

Safety & Tolerability
Thirty Eight (38) patients were evaluable for safety (20 CLL/SLL patients, and 18 NHL patients). The triple combination appeared to be well tolerated in all patients, with neutropenia (32% all grades, 18% Grade 3/4) and pneumonia (18% all grades, 11% Grade 3/4), being the only Grade 3/4 AEs in > 10% of patients. Of the 38 patients treated to date, only two AEs (sepsis and pneumonia) led to treatment discontinuation. Median time on study was 11.1 months (range 0.4 – 30+ months) with 81% of patients on study > 6 months.

Clinical Activity
Clinical activity was observed at all dose levels with 36 of 38 patients evaluable for efficacy (19 CLL/SLL patients, and 17 NHL patients), with 2 patients having discontinued prior to first efficacy assessment (1 pneumonia, and 1 investigator discretion).

CLL/SLL Efficacy highlights include:

• 100% (19 of 19) Overall Response Rate (ORR), including a 32% Complete Response (CR) rate observed in patients with CLL/SLL (4 of 6 CR’s pending marrow confirmation)
• 50% of the CLL patients had a 17p and/or 11q deletion
• 3 CLL patients had prior BTK and/or PI3Kδ inhibitor therapy, including one patient refractory to both idelalisib and ibrutinib who attained a complete response (ongoing for 1.5+ years)

NHL Efficacy highlights include:

• Response Rates observed in patients with NHL:

100% (2 of 2) ORR, including one CR in patients with Marginal Zone Lymphoma (MZL)
100% (4 of 4) ORR, including 50% CR rate in patients with Mantle Cell Lymphoma (MCL)
80% (4 of 5) ORR, including 20% CR rate in patients with Follicular Lymphoma (FL)
17% (1 of 6) ORR in patients with Diffuse Large B-cell Lymphoma (DLBCL)
• FL patients were heavily pretreated including 2 with prior Autologous Stem Cell Transplant (ASCT), 1 refractory to prior ibrutinib, and 1 with 5 prior lines of rituximab based therapy
• DLBCL patients had a median of 4 prior therapies, and 4 of 6 were of non-GCB subtype

Poster Presentation: KI intolerance study: A phase 2 study to assess the safety and efficacy of TGR-1202 in pts with chronic lymphocytic leukemia (CLL) who are intolerant to prior BTK or PI3K-delta inhibitor therapy (Abstract: TPS7569)

This poster details the study design for an ongoing Phase II, multicenter, single-arm trial of TGR-1202 (umbralisib) in CLL patients requiring therapy who are intolerant to prior Kinase Inhibitor (KI) therapy. The study will enroll approximately 50 patients who have discontinued prior therapy with a BTK or PI3K delta inhibitor due to intolerance and not disease progression. The primary objective of the study is to determine the progression free survival (PFS) of TGR-1202 in this patient population. Key secondary objectives such as overall response rate, duration of response, time to treatment failure and safety of TGR-1202 as compared to the prior KI therapy will also be evaluated.

PRESENTATION DETAILS:

The above referenced presentations are now available on the Publications page, located within the Pipeline section, of the Company’s website at www.tgtherapeutics.com/publications.cfm.