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TG Therapeutics, Inc. Announces Follow-Up Data for Combination of TGR-1202 (umbralisib) plus Ibrutinib in Patients with Relapsed or Refractory CLL and MCL at the 14th International Conference on Malignant Lymphoma

On June 14, 2017 TG Therapeutics, Inc. (NASDAQ:TGTX), reported updated clinical data from its ongoing Phase I/Ib trial of TGR-1202 (umbralisib), the Company’s oral, next generation PI3K delta inhibitor, in combination with ibrutinib, a BTK inhibitor, in patients with Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL) (Press release, TG Therapeutics, JUN 14, 2017, View Source [SID1234519542]). This study is being run in collaboration with the Blood Cancer Research Partnership (BCRP) and Dana-Farber Cancer Institute (DFCI), in Boston, MA. Data from this trial were presented today by the Principal Investigator, Matthew S. Davids, MD, of Dana-Farber Cancer Institute, during an oral session at the 14th International Conference on Malignant Lymphoma (ICML), in Lugano, Switzerland.

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer stated, "We continue to be impressed with the safety, tolerability and activity of the combination of TGR-1202 and ibrutinib. With this all oral combination, we are seeing high response rates, including in those patients with prior PI3K inhibitor or ibrutinib exposure. Additionally, the combination was well tolerated with over 30 patients now treated and for durations upwards of 2.5 years in this independently run, investigator initiated study." Mr. Weiss continued, "We want to thank Dr. Davids and his collaborators at DFCI and the Leukemia & Lymphoma Society for leading this important investigator driven research. Dr. Davids’ research provides another important piece of information as we try to identify the best way to use these drugs, alone or in combination. These data complement the recently reported results at ASCO (Free ASCO Whitepaper) from the triple combination of TGR-1202, ibrutinib and TG-1101, our anti-CD20 monoclonal antibody, which showed that the three-drug combination was also well-tolerated and appeared to induce even higher rates of response, with 100% ORR by iwCLL criteria and deeper responses with 26% of the CLL patients achieving a CR. We look forward to continuing to explore these combinations to drive better outcomes for patients."

Highlights from today’s presentation include the following:

Oral Presentation: Updated results of a multicenter phase I/Ib study of TGR-1202 in combination with ibrutinib in patients with relapsed or refractory MCL or CLL (Abstract #040)

This oral presentation includes data from patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL) or Mantle Cell Lymphoma (MCL) treated with TGR-1202 in combination with ibrutinib. 32 patients were evaluable for safety (18 CLL patients and 14 MCL patients), of which 31 patients were available for efficacy (17 CLL patients and 14 MCL patients). CLL patients had a median of 1.5 prior lines of therapy (range 1-6), with 2 patients receiving prior ibrutinib and 4 receiving prior PI3K inhibitors. MCL patients had a median of 3 prior lines of therapy (range 2-5), with 2 patients also receiving prior ibrutinib.

Highlights from this oral presentation include:

94% (16 of 17) of CLL patients achieved a Complete Response (CR), Partial Response (PR), or a Partial Response with lymphocytosis (PR-L), with 1 patient achieving a CR and 3 additional patients with radiographic CR
All 3 patients with prior PI3K inhibitor therapy that were evaluable for efficacy, and 1 of the 2 patients with prior ibrutinib exposure responded
1-year progression free survival (PFS) for CLL is 88% and overall survival (OS) at 1-year is 94%, (n=17), with the longest patient on study 29.5+ months
79% (11/14) ORR in patients with MCL, including 1 CR and 1 additional radiographic CR, with marked clinical benefit observed in two additional patients
Median PFS and OS for MCL is 8.4 and 11.6 months, respectively (n=11)
The combination appears well tolerated across all patients with no grade 3/4 transaminitis (liver toxicity), diarrhea, colitis or pneumonitis observed
PRESENTATION DETAILS:

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.

Oxford BioMedica Notes Findings on CTL019 from Phase II JULIET Study Presented at the 14th Meeting of International Conference on Malignant Lymphoma (ICML)

On June 14, 2017 Oxford BioMedica plc ("Oxford BioMedica" or "the Group") (LSE:OXB), a leading gene and cell therapy group, reported the findings reported by Novartis on its global multi-centre Phase II JULIET study evaluating the efficacy and safety of CTL019 (tisagenlecleucel-T), an investigational chimeric antigen receptor T cell (CAR-T) therapy, in adult patients with relapsed and refractory (r/r) diffuse large B-cell lymphoma (DLBCL) (Press release, Oxford BioMedica, JUN 14, 2017, View Source [SID1234519541]). The study met its primary objective at interim analysis.

Oxford BioMedica is the sole manufacturer of the lentiviral vector expressing CTL019 for Novartis. The commercial launch of CTL019 is anticipated by Novartis later this year and Oxford BioMedica will receive undisclosed royalties on potential future sales of Novartis CAR-T products.

The findings were presented during an oral session at 15:40 CET on Wednesday 14th June 2017 at the 14th International Conference on Malignant Lymphoma (ICML) meeting (Abstract #007).

Novartis reported the interim analysis of the global multi-centre Phase II JULIET study which showed a 3-month Overall Response Rate (ORR) of 45% (23 of the 51 patients evaluated), with 37% achieving a Complete Response (CR) and 8% achieving a Partial Response (PR), respectively. CR remained stable from three months through data cut off among the patient group. Among 51 patients with >3 month follow-up or earlier discontinuation, best ORR was 59% (95% CI, 44%-72%; P<0.0001) with 43% achieving CR and achieving 16% PR. CR and PR rates at 3 months were 37% and 8% respectively. Cytokine Release Syndrome (CRS) occurred in 57% of infused patients (17% grade 3, 9% grade 4); no CRS associated deaths occurred. No cerebral oedema was reported. Three patients died from disease progression, within 30 days of infusion. No deaths were attributed to CTL019. The abstract is available online here: View Source

The overall response rate seen in this early analysis is impressive for these heavily pre-treated patients with relapsed/refractory DLBCL, who have limited treatment options. The full JULIET primary analysis is expected to be available later this year and will serve as the basis for US and EU regulatory submissions.

John Dawson, Chief Executive Officer of Oxford BioMedica, commented: "We are pleased that Novartis has reported these additional strong data with CTL019 in another indication, r/r DLBCL, which is a much larger target patient population than for r/r ALL. We continue to work closely with Novartis in delivering the lentiviral vector across their CTL019 franchise, a product group described earlier this year, by Novartis, as having "blockbuster" potential."

argenx presents update on Phase I data from ARGX-110 expansion study in patients with cutaneous T-cell lymphomas at the International Conference of Malignant Lymphoma (ICML)

On June 14, 2017 rgenx (Euronext & Nasdaq: ARGX), a clinical-stage biotechnology company developing a deep pipeline of differentiated antibody-based therapies for the treatment of severe autoimmune diseases and cancer, today presented updated data from its Phase 1b expansion study of ARGX-110 in patients with different subtypes of relapsed/refractory cutaneous T-cell lymphoma (CTCL) and various disease stages, at the International Conference of Malignant Lymphoma (ICML) in Lugano, Italy (Filing, 6-K, argenx, JUN 14, 2017, View Source [SID1234519530]).

“Analysis of the skin biopsies continues to strengthen the biological rationale of targeting CD70 with ARGX-110. Clinical activity was observed in patients across different CTCL subtypes (mycosis fungoides, Sézary syndrome, panniculitis-like TCL) and different disease stages whilst the drug shows a favorable safety and tolerability profile,” commented Nicolas Leupin, Chief Medical Officer of argenx. “Improved pruritis was observed in some of the patients and will be further monitored to explore ARGX-110 modes of action in skin of CTCL patients.”

The updated data from the currently ongoing Phase Ib study continue to show evidence of clinical and/or biological anti-tumor activity with ARGX-110. We observed partial response and stable disease, respectively, in three and seven out of 16 patients with highly relapsed/refractory CTCL and confirmed overexpression of CD70. Treatment-emerging adverse events were reported for six out of 16 patients. The poster presented at ICML can be accessed from the “Downloads” section of the argenx website.

In April 2017, argenx announced the initiation of a Phase II trial of ARGX-110 as a monotherapy in relapsed/refractory CTCL patients, in order to further examine the activity of the product candidate, using the optimal dose and biomarker panel determined during the Phase Ib trial.

About ARGX-110

ARGX-110 is a SIMPLE Antibody targeting CD70, an immune checkpoint target involved in hematological malignancies, several solid tumors and severe autoimmune diseases. ARGX-110 is designed to: i) block CD70, ii) kill cancer cells expressing CD70 through antibody-dependent cellular phagocytosis and iii) restore immune surveillance against solid tumors (Silence K. et al. mAbs 2014; 6 (2):523-532). ARGX-110 is currently being evaluated in patients with hematological and solid tumors. ARGX-110 is currently being evaluated in a Phase II trial in combination with azacitidine in patients with newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) and a Phase II trial in patients with relapsed/refractory CTCL. Preclinical work on ARGX-110 in AML was performed in collaboration with the Tumor Immunology Lab of Prof. A. F. Ochsenbein at the University of Bern, who won, together with Prof. Manz from the University Hospital of Zürich, the prestigious 2016 Otto Naegeli Prize for his breakthrough research on CD70/CD27 signaling with therapeutic potential for cancer patients.

Helsinn Group and MEI Pharma Announce First Patient Dosed in Phase 2 Dose-Optimization Study of Pracinostat and Azacitidine in Myelodysplastic Syndrome

On June 14, 2017 Helsinn, a Swiss pharmaceutical group focused on building quality cancer care products, and MEI Pharma, Inc. (Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, reported that the first patient has been dosed in a Phase 2 dose-optimization study of pracinostat in combination with azacitidine in patients with higher risk myelodysplastic syndromes (MDS) who are previously untreated with hypomethylating agents (HMAs) (Press release, MEI Pharma, JUN 14, 2017, View Source [SID1234519540]).

The two-stage study will be conducted at approximately 25 sites and is expected to enroll up to 120 patients with high and very high risk MDS per the Revised International Prognostic Scoring System (IPSS-R). The high and very high risk groups represent the highest unmet need in MDS, with median survival estimates of only 1.6 years and 0.8 years, respectively1. The cost of this study will be shared by Helsinn and MEI Pharma. Data from the first stage is expected in the first quarter of 2018.

"Based on our clinical experience with the combination, we believe that a reduced dose of pracinostat has the potential to improve tolerability in patients with higher risk MDS, thereby improving efficacy of the combination compared to azacitidine alone," said Robert D. Mass, MD, Chief Medical Officer of MEI Pharma. "We look forward to working with the study’s investigators and Helsinn to evaluate this hypothesis in the clinic while we await the outcome of our pivotal Phase 3 study of the combination in acute myeloid leukemia (AML)."

Sergio Cantoreggi, PhD., Helsinn Group Chief Scientific Officer said, "We are pleased to announce that the first patient with higher risk myelodysplastic syndromes has been dosed in this Phase 2 dose-optimization study of pracinostat in combination with azacitidine. Pracinostat is a promising late-stage asset and a key part of Helsinn’s broadened focus into therapeutic clinical development and we look forward to seeing the results in early 2018."

In a recently published, placebo-controlled Phase 2 study (MEI-003) conducted in 102 patients with intermediate-2 and high risk MDS, pracinostat (60mg) and azacitidine failed to increase the complete response rate, the study’s primary endpoint, compared to azacitidine and placebo2. Drug discontinuation within the first two months of treatment, due to poor tolerability (primarily fatigue and myelosuppression), occurred twice as frequently in the pracinostat group compared to placebo. A sensitivity analysis, including 54 patients who received at least four cycles of study therapy (pracinostat or placebo) and azacitidine showed a trend for better progression-free survival and overall survival (hazard ratio = 0.37 and 0.59, respectively) compared to the control group. These data suggest that insufficient exposure to treatment may have limited the overall efficacy of the combination and are consistent with recently presented findings from an analysis of patients in a Phase 2 study of pracinostat and azacitidine in AML which showed that continued treatment increases the rate of minimal residual disease clearance3.

This two-stage, Phase 2 study will investigate a pracinostat dose of 45 mg, 25% lower than the dose used in study MEI-003, in combination with the standard dose of azacitidine to determine whether lowering the pracinostat dose in a higher risk patient population can improve the tolerance of the combination while achieving a clinically meaningful improvement in efficacy.

The first stage of the study will be open-label, single arm in up to 40 patients to assess if the lower pracinostat dose will result in a discontinuation rate that approximates the rate that was observed with azacitidine alone in study MEI-003 (10%). If results from the first stage support expansion of enrollment, the second stage will be randomized and placebo-controlled to confirm the discontinuation rate in a blinded setting and to provide data on safety and efficacy.

The primary endpoints of the study are 1) safety and tolerability and 2) overall response rate, defined as complete remission (CR), partial remission (PR) and marrow CR. Secondary endpoints include CR rate, overall hematologic improvement (HI) response rate, clinical benefit rate (defined as rate of CR + PR + HI + Marrow CR), rate of cytogenetic complete response/remission, duration of response, rate of leukemic transformation, event-free survival, progression-free survival and overall survival.

About Higher Risk MDS
Higher risk MDS (high and very high risk in the IPSS-R classification) is a serious medical condition, with median survival of less than 18 months. The only curative therapy is allogeneic stem cell transplantation (SCT), however most patients with MDS are not candidates for SCT given their typically advanced age, comorbidities and lack of a suitable donor. Standard therapy with HMAs in higher risk MDS provides modest responses, though azacitidine has been shown to improve survival when compared to conventional care regimens4. Patients who do not respond to HMAs or progress after therapy with HMAs have a very poor outcome, with a median survival of less than one year5.

About Pracinostat
Pracinostat is an oral histone deacetylase (HDAC) inhibitor that is in late stage clinical development. The U.S. Food and Drug Administration has granted Breakthrough Therapy Designation for pracinostat in combination with azacitidine for the treatment of patients with newly diagnosed AML who are ≥75 years of age or unfit for intensive chemotherapy. In August 2016, Helsinn and MEI Pharma entered into an exclusive license, development and commercialization agreement for pracinostat in AML and other potential indications. The deal provides the complementary resources from both organizations to advance pracinostat into Phase III clinical development in AML and expand into additional areas of clinical development, including MDS. Pracinostat is an investigational agent and is not approved for commercial use in the U.S.

Kura Oncology Presents Preliminary Clinical and Preclinical Data for Tipifarnib in the Treatment of Relapsed or Refractory Peripheral T-Cell Lymphoma

On June 14, 2017 Kura Oncology, Inc. (NASDAQ:KURA), a clinical stage biopharmaceutical company focused on the development of precision medicines for oncology, reported that clinical and preclinical data for tipifarnib in the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL) was presented at the International Conference on Malignant Lymphoma (ICML) being held June 14-17, 2017 in Lugano, Switzerland (Press release, Kura Oncology, JUN 14, 2017, View Source [SID1234519539]).

Kura Oncology is conducting preclinical and clinical development studies in clinical indications where tipifarnib has previously shown signs of activity with the goal to identify and validate biomarkers associated with the observed clinical activity of tipifarnib. The preliminary Phase 2 clinical data presented at ICML indicate that tipifarnib has antitumor activity in PTCL, particularly in patients with angioimmunoblastic T-cell lymphoma (AITL) histology and PTCL-NOS (Not Otherwise Specified) histology with high levels of CXCL12 gene expression and absence of single nucleotide gene variations in the 3′-untranslated region of the CXCL12 gene.

"Patients with PTCL have a poor overall survival of about 40%. Effective options for relapsed patients are limited and new drugs with novel mechanisms of action are needed," said Thomas Witzig, M.D., Professor of Medicine at the Mayo Clinic and a lead investigator on the study. "The preliminary results of this study are exciting because they may define a molecular mechanism of action and characterize a subgroup of patients that derive significantly greater clinical benefit from a targeted therapy such as tipifarnib."

"These results identify the CXCL12/CXCR4 pathway as a potential target of tipifarnib. CXCL12 is secreted in large amounts by lymph nodes, bone marrow stroma, liver, and lung, and plays key roles in tumor invasion, bone marrow homing and site of metastasis. Its receptor, CXCR4, signals in part through HRAS, a protein that is uniquely farnesylated, and it is one of the most frequently over-expressed chemokine receptors in malignant cells," said Antonio Gualberto, M.D., Ph.D., Chief Medical Officer at Kura Oncology. "Based on our preliminary data, we believe CXCL12/CXCR4 may have the potential to unlock the therapeutic value of farnesyl transferase inhibition in a number of tumor indications."

Patients in the Phase 2 study received tipifarnib 600 mg orally twice daily on days 1-7 and 15-21 in 28-day cycles. Among the 18 patients in stages 1 and 2 of this trial, 3 achieved a partial response (PR), and two of the PRs occurred in the two patients on study with AITL. An additional 4 patients had meaningful tumor size reductions and prolonged disease stabilization. In addition, tipifarnib was generally well-tolerated with adverse events consistent with its known safety profile and no patient discontinued due to adverse events. The Phase 2 study has been extended to enroll an additional 12 patients with AITL histology aimed at confirming the preliminary observations and validating CXCL12 as a biomarker of tipifarnib activity.

The preliminary results from the Phase 2 study in PTCL were also selected for a poster presentation at the 22nd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) taking place June 22-25, 2017 in Madrid, Spain.