On November 27, 2017 TG Therapeutics (NASDAQ:TGTX) reported that along with SWOG, the global cancer clinical trials group funded by the National Cancer Institute (NCI), it has initiated a three arm Phase II trial evaluating the combination of TGR-1202 (umbralisib), the Company’s PI3K delta inhibitor, plus obinutuzumab, compared to the combination of obinutuzumab plus lenalidomide, and obinituzumab plus CHOP, in patients with early relapsing or refractory Follicular Lymphoma (FL) (Grade I, II, IIIa) (Press release, TG Therapeutics, NOV 27, 2017, View Source [SID1234522247]). Target enrollment will be 50 patients per arm.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The primary outcome of this study is to assess the Complete Response (CR) rate following six cycles of treatment. Key secondary outcomes include ORR, DOR and PFS. The safety profile of each of these regimens will also be evaluated. The study will be independently run by SWOG, which has received NC funding since 1956. TG has agreed to provide TGR-1202 free of charge for use in the study. The goal of the study is to identify safe and effective novel combinations that can be used to manage these challenging early relapsing Follicular Lymphoma (FL) patients. The study is now open at over 100 hospitals, cancer centers, and other clinical sites across the US. More information about the study can be found at www.clinicaltrials.gov, Identifier NCT03269669.

Dr. Paul Barr, director of the Clinical Trials Office for Wilmot Cancer Institute at the University of Rochester Medical Center and leader of this Phase II trial, stated: "This is an extremely important study for patients with early, relapsed follicular lymphoma because they need new treatment options. Follicular lymphoma patients who relapse within two years of front-line immuno-chemotherapy are generally recognized to have the poorest outcomes. We chose these arms based on the best available clinical research suggesting these were the most promising targets for therapeutic intervention in the treatment of FL. The PI3K delta class have shown impressive single agent activity in the treatment of FL, however, the safety profile of the currently available first generation PI3K delta’s are not ideal. We are pleased that TG has agreed to supply TGR-1202 for this study, as this agent appears to offer a unique safety profile compared to prior PI3K-delta inhibitors while still maintaining encouraging clinical activity in patients with NHL. We are very excited that enrollment has now begun and expect a very rapid enrollment period."

Michael S. Weiss, Executive Chairman and Chief Executive Officer, stated, "We are extremely pleased that SWOG has selected TGR-1202 for inclusion in this important trial. We believe this trial will showcase treatment strategies that may significantly improve outcomes for early relapsing patients and in particular, demonstrate the utility of TGR-1202 in FL. To us, the inclusion of TGR-1202 validates our belief of best-in-class qualities of TGR-1202 and the importance of PI3K delta class in FL."

On November 27, 2017 Nektar Therapeutics (Nasdaq: NKTR) reported that its corporate presentation will be webcast at the upcoming Piper Jaffray 29th Annual Healthcare Conference in New York City on Tuesday, November 28, 2017 at 5:10 p.m. ET (Press release, Nektar Therapeutics, NOV 27, 2017, View Source [SID1234522262]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The presentation will be accessible via a Webcast through a link posted on the Investors, Events Calendar section of the Nektar website: View Source This Webcast will be available for replay until December 29, 2017.

On November 27, 2017 Idera Pharmaceuticals, Inc. (NASDAQ:IDRA), a clinical-stage biopharmaceutical company developing toll-like receptor and RNA therapeutics for patients with cancer and rare diseases, reported that the company will participate in a fireside chat, led by Vincent Milano, Idera’s Chief Executive Officer, at the 29th Annual Piper Jaffray Healthcare Conference on Wednesday, November 29, 2017 at 10:00 a.m (Press release, Idera Pharmaceuticals, NOV 27, 2017, View Source [SID1234522265]). Eastern Time at the Lotte New York Palace Hotel in New York City.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Live audio webcast of Idera’s presentations will be accessible in the Investors and Media section of Idera’s website at View Source Archived versions will also be available on the Company’s website after the event for 90 days.

On November 27, 2017 AstraZeneca reported the submission of a supplemental new drug application (sNDA) to Japan’s Pharmaceuticals and Medical Devices Agency for the use of Tagrisso (osimertinib), a third-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with clinical activity against central nervous system (CNS) metastases, for the 1st-line treatment of patients with inoperable or recurrent EGFR mutation-positive (EGFRm) non-small cell lung cancer (NSCLC) (Press release, AstraZeneca, NOV 27, 2017, View Source [SID1234522242]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Japan sNDA is based on data from the Phase III FLAURA trial, in which Tagrisso significantly improved progression-free survival (PFS) compared to current 1st-line EGFR-TKIs, erlotinib or gefitinib, in previously-untreated patients with locally-advanced or metastatic EGFRm NSCLC.

NOTES TO EDITORS

About NSCLC

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-quarter of all cancer deaths, more than breast, prostate and colorectal cancers combined. Approximately 10-15% of patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC. These patients are particularly sensitive to treatment with currently-available EGFR-TKIs, which block the cell-signalling pathways that drive the growth of tumour cells. However, tumours almost always develop resistance to EGFR-TKI treatment, leading to disease progression. Approximately half of patients develop resistance to approved EGFR-TKIs such as gefitinib and erlotinib due to the resistance mutation, EGFR T790M.Tagrisso also targets this secondary mutation that leads to disease progression. There is also a need for medicines with improved CNS efficacy, since approximately 25% of patients with EGFR-mutated NSCLC have brain metastases at diagnosis, increasing to approximately 40% within two years of diagnosis.

About Tagrisso

Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI designed to inhibit both EGFR-sensitising and EGFR T790M-resistance mutations, with clinical activity against CNS metastases. Tagrisso 40mg and 80mg once-daily oral tablets have been approved in more than 60 countries, including the US, EU, Japan and China, for patients with EGFR T790M mutation-positive advanced NSCLC. Tagrisso is also being investigated in the adjuvant setting and in combination with other treatments.

About the FLAURA trial

The FLAURA trial assessed the efficacy and safety of Tagrisso 80mg once daily vs standard-of-care EGFR-TKIs (either erlotinib [150mg orally, once daily] or gefitinib [250mg orally, once daily]) in previously-untreated patients with locally-advanced or metastatic EGFR-mutated NSCLC. The trial was a double-blinded, randomised trial, with 556 patients across 29 countries.

About AstraZeneca in Lung Cancer

AstraZeneca is committed to developing medicines to help every patient with lung cancer. We have two approved medicines and a growing pipeline that targets genetic changes in tumour cells and boosts the power of the immune response against cancer. Our unrelenting pursuit of science aims to deliver more breakthrough therapies with the goal of extending and improving the lives of patients across all stages of disease and lines of therapy.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s five Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

On November 27, 2017 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported the synergistic effect of combining Inovio’s TERT (telomerase reverse transcriptase) cancer immunotherapy in combination with a checkpoint inhibitor in preclinical tumor model (Press release, Inovio, NOV 27, 2017, View Source [SID1234522244]). The combination therapies resulted in robust anti-tumor effects and showed significant improvement in survival compared to either therapy alone. Preclinical TERT study results were detailed in a paper published in the most recent edition of Molecular Therapy entitled, "Synergy of Immune Checkpoint Blockade with a Novel Synthetic Consensus DNA Vaccine Targeting TERT," by Inovio and its collaborators at the Wistar Institute.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Dr. J. Joseph Kim, President and CEO, said, "The synergistic anti-tumor effect observed in this published preclinical study provides Inovio with added confidence in the company’s recently initiated efficacy studies combining checkpoint inhibitors and INO-5401, Inovio’s cancer immunotherapy which includes three of Inovio’s top SynCon cancer antigens – hTERT, WT1, and PSMA, which are over-expressed in multiple tumor types. MedImmune, Regeneron and Genentech have all turned to Inovio’s DNA-based immunotherapy products to evaluate increased response rates in combination with their checkpoint inhibitors. We look forward in sharing combination data from these efficacy trials when they become available."

Inovio is currently evaluating its human TERT (hTERT) immunotherapy, INO-1400, as a mono-therapy, in nine different solid tumors including breast, lung and pancreatic cancers. A recent poster presentation at the SITC (Free SITC Whitepaper) annual conference demonstrated that INO-1400 generated hTERT-specific T cell immune responses in patients. Furthermore, hTERT along with WT1 and PSMA antigens also comprise the new multi-antigen immunotherapy INO-5401, which is being evaluated in two separate phase 1/2 efficacy trials in combinations PD-L1 (with Genentech) and PD-1 (with Regeneron) checkpoint inhibitors in metastatic bladder cancer and in newly diagnosed Glioblastoma multiforme (GBM), respectively.

INO-5401 is being tested in combination with PD-1/PD-L1 inhibitors to bring about better anti-tumor effects in metastatic bladder and GBM. Nearly 430,000 new cases of urinary bladder cancer are diagnosed each year worldwide; it accounts for about 165,000 deaths worldwide annually. Advanced unresectable or metastatic UC remains a high unmet medical need as survival remains poor for most patients. The approval of several checkpoint inhibitors for advanced unresectable or metastatic UC has improved response and survival rates for some patients, however, the majority (~80%) of patients do not experience meaningful clinical responses to checkpoint inhibitor monotherapy. GBM is the most aggressive brain cancer and its prognosis is extremely poor. The median overall survival for patients receiving standard of care therapy is approximately 15 months and the average five-year survival rate is less than three percent. Clinical responses to checkpoint inhibitors in GBM patients have been poor overall (ORR<10%). Both of these INO-5401 combination studies are designed to test the synergistic anti-tumor effects of the combination therapies.

Significant early checkpoint combination effects were seen in a clinical study of another Inovio T-cell generating product, INO-3112 (licensed to MedImmune and now called MEDI0457). In a phase 1 study of MEDI0457 in 22 HPV-positive patients with squamous cell carcinoma of the head and neck, Inovio has previously demonstrated that this cancer immunotherapy generated robust antigen-specific CD8+ killer T cell responses measured in both tumor tissue and peripheral blood. One patient who initially displayed a slight increase in T cell immune responses developed progressive disease at 11 months into the study. The patient subsequently received nivolumab, a PD-1 checkpoint inhibitor and sustained complete response after only four doses of nivolumab. This patient continues on therapy with no evidence of disease, 16 months after initiation of nivolumab. Medimmune is currently conducting a separate phase 1/2 efficacy trial combining its PD-L1 inhibitor (durvalumab) with MEDI0457 in 50 metastatic HPV-associated head and neck cancer patients to evaluate the clinical efficacy of the combination treatment. Head and neck cancer caused by HPV is the fastest growing cancer in men today, and the checkpoint inhibitor therapies alone have only been positive in limited percentage (ORR<20%) of treated patients.

This published paper highlights the potential benefits of DNA immunotherapy/immune checkpoint blockade combinations using PD-1 or CTLA4 checkpoint inhibitors in patients that respond poorly to immune checkpoint blockade alone, and allow for better rational design of combination therapies. Furthermore, these results suggest that this synergistic anti-tumor effect is due to the effect of immune checkpoint blockade on expanding effector T cells generated from the TERT therapy in the tumor microenvironment rather than boosting vaccine responses in the periphery.