On June 4, 2019 Asuragen, Inc., a molecular diagnostics company delivering easy-to-use products for complex testing in genetics and oncology, reported publication of a study demonstrating a single next-generation sequencing (NGS) workflow for the sensitive and accurate detection of DNA and RNA variants associated with non-small cell lung cancer (NSCLC) in the journal Translational Oncology (View Source) (Press release, Asuragen, JUN 4, 2019, View Source [SID1234536880]). The article, titled "An Integrated Next-Generation Sequencing System for Analyzing DNA Mutations, Gene Fusions, and RNA Expression in Lung Cancer," describes the targeted analysis of 190 loci from low-input and low-quality NSCLC specimens using a rapid and standardized NGS procedure that is compatible with existing laboratory instrumentation.

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Lung cancer is the leading cause of cancer-related death worldwide and NSCLC accounts for approximately 85% of all lung cancer cases. A number of targeted therapies for DNA and RNA variants in NSCLC are now available, but their timely detection is complicated by segregated NGS methods for DNA versus RNA and by limitations in biopsy tissue and nucleic acid quality to support split workflows. To address these challenges, the publication describes a unified DNA/RNA NGS assay that covers hotspot mutations in 20 genes, including EGFR, KRAS, BRAF, and PIK3CA, as well as 107 RNA fusion variants recurrent in NSCLC, such as ALK, RET, ROS1, and NTRK1, and MET exon 14 skipping events. RNA quantification also includes 23 transcripts with prognostic and theranostic value, such as PD-L1, PD-L2, INFG, and CTLA4 that are important in assessing T-cell-inflamed phenotypes and the impact of immune checkpoint inhibitor therapies. Analysis is achieved using proprietary software to automate variant calls from total nucleic acid, resulting in quantification of SNVs, INDELs, CNVs, fusions, splice variants, and expression targets – all within a single, harmonized NGS run. By querying functional input copies, sequence quality, sample-specific error rates, local sequence complexity, and coverage depth, the software is an essential component of the overall system and helps ensure robust and accurate results.

In the study, over 200 formalin-fixed, paraffin-embedded (FFPE) surgical resections and core needle biopsies provided by collaborators at MD Anderson Cancer Center were tested. The results were consistent with variant prevalence established by large, international consortia such as TCGA, demonstrating mutual exclusivity between driver events and distinct molecular subtypes for adenocarcinoma and squamous cell carcinoma. Sequence variants in fine needle aspirate (FNA) smears from BATTLE-2 clinical trial subjects were in 97% agreement with matched FFPE specimens tested by the FoundationOne NGS Assay, even though the FNA biopsies had substantially fewer cells available for analysis.

"Our study with Asuragen demonstrates the continued evolution of NGS methods to reliably quantify different types of cancer-associated variants across both DNA and RNA that are relevant to precision medicine," commented Ignacio I. Wistuba, MD, professor and chair, Department of Translational Molecular Pathology at The University of Texas MD Anderson Cancer Center. "This integrated and rapid approach may help clinicians and laboratories maximize the actionable information they can recover from small patient biopsies, and accelerate turnaround times for results and decision-making."

This study was funded in part by a Cancer Prevention and Research Institute of Texas (CPRIT) Product Development Research grant.

On June 4, 2019 NantKwest Inc. (Nasdaq:NK) reported that its strategic partner Viracta Therapeutics presented updated clinical data on its HDAC inhibitor, nanatinostat (VRx-3996) at the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago, IL, from May 31st – June 4th, 2019 (Press release, NantKwest, JUN 4, 2019, View Source [SID1234536879]).

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In April 2017, NantKwest announced that it was the lead investor in Viracta’s Series B financing round. Concurrent with the financing, NantKwest secured an exclusive license with commercialization rights to nanatinostat for use in combination with natural killer (NK) cell therapies, including NantKwest’s NK cell platforms.

Nanatinostat is a Class 1 histone deacetylase (HDAC) inhibitor currently in phase Ib/II clinical trials (NCT03397706). In preclinical studies, nanatinostat has been shown to reactivate silenced transgenes in tumor cells thereby turning them into preferential targets for NK cell killing, while also serving to broadly stimulate a patient’s immune system, offering the potential for improved clinical responses in cancer patients.

The activity of HDAC inhibitors are believed to be based on the upregulation of natural killer group 2D (NKG2D) ligand expression on cancer cells, which serve as "eat-me" signals for NK cells and can drive NK proliferation, activation and cancer cell killing.

NantKwest is preparing to initiate clinical trials that include nanatinostat in combination with its haNK and t-haNK cell therapy platforms, which we believe will work synergistically to enhance the efficacy of the company’s NK cell therapies and further distinguish us in the market.

Interim results presented at the 2019 annual ASCO (Free ASCO Whitepaper) meeting from the phase Ib portion of the ongoing phase Ib/II clinical trial of nanatinostat was in combination with the antiviral valganciclovir for the treatment of relapsed/refractory Epstein Barr Virus (EBV)-associated lymphomas. Three doses of the combination were evaluated with responses seen at all dose levels. Both drugs are taken orally and can be administered in an out-patient setting.

EBV-associated cancers are known to be an extremely difficult cancer to treat. Early clinical data with the combination of nanatinostat and anti-viral therapy in EBV-associated lymphoma from the phase Ib/II study has provided encouraging efficacy signals. Currently, there are no approved treatments for EBV-associated lymphomas that specifically target the virus.

The combination therapy produced an objective response rate (ORR) of 58%, a complete response rate (CR) of 33% and a disease stabilization rate (DSR) of 75%. Based on these encouraging results, Viracta anticipates advancement of the clinical trial to the phase II stage that will evaluate intermittent dosing of nanatinostat (4 days on and 3 days off) in combination with daily valganciclovir.

Patrick Soon-Shiong, M.D., Chairman and CEO of NantKwest commented, "EBV-associated lymphomas represent a heterogenous group of cancers that are often aggressive and poorly responsive to available therapy. In this phase Ib stage, we are pleased to see encouraging objective responses including a 33% complete response rate in relapsed/resistant EBV positive cancer patients. We look forward to our continued partnership with Viracta to transition to phase II clinical trials, while also moving nanatinostat forward in combination with NantKwest’s haNK and t-haNK cell therapies."

Ivor Royston, M.D., Viracta’s CEO added, "Our ASCO (Free ASCO Whitepaper) presentation and clinical trial update highlights the potential of our proprietary ‘Kick & Kill’ therapeutic approach to treat a wide range of EBV positive cancer patients, with responses seen across all doses in both T cell and B cell lymphomas in our ongoing phase Ib/II study. "This data enable us to move forward with the phase II portion of our study with a well-tolerated dose combination of nanatinostat with valganciclovir, which we expect to initiate in the third quarter of 2019."

About Nanatinostat

Nanatinostat (VRx-3996) is a histone deacetylase (HDAC) inhibitor that is being investigated in a range of clinical indications. Nanatinostat is selective for Class 1 HDACs, including isoforms targeted in Viracta’s "Kick & Kill" therapeutic approach. Viracta is investigating nanatinostat in a phase Ib/II clinical study [NCT03397706] in combination with an antiviral valganciclovir for the treatment of EBV-associated cancers. Both drugs are taken orally and can be given on an out-patient basis. Recently, the nanatinostat plus valganciclovir combination therapy received Orphan Drug Designation (ODD) from the U.S. Food & Drug Administration (FDA) for three sub-types of EBV-associated cancers: post-transplant lymphoproliferative disorder (PTLD), plasmablastic lymphoma, and angioimmunoblastic T cell lymphoma.

About EBV-Associated Cancers

Approximately 95% of the world’s adult population is infected with Epstein-Barr Virus (EBV). Infections are commonly asymptomatic or associated with mononucleosis. Following infection, the virus remains latent in a small subset of lymphatic cells for the duration of the patients’ life. Cells containing latent virus are increasingly susceptible to malignant transformation. Patients who are immunocompromised are at an increased risk of developing EBV lymphomas. In addition, EBV is also associated with a variety of solid tumors, including nasopharyngeal carcinoma and gastric cancer.

On June 4, 2019 IMV Inc. ("IMV" or the "Corporation") (Nasdaq: IMV; TSX: IMV), a clinical stage immunotherapy company, reported that it will hold a conference call and webcast on Wednesday, June 12, 2019, at 8:00 a.m. ET (Press release, IMV, JUN 4, 2019, View Source [SID1234536878]). This call will provide an update on its ongoing phase 2 clinical trials with Merck’s Keytruda in diffuse large B-cell lymphoma (DLBCL).

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Financial analysts are invited to join the conference call by dialing (866) 211-2304 (U.S. and Canada) or (647) 689-6600 (International) using the conference ID: 9685423

Other interested parties will be able to access the live audio webcast at this link: View Source The webcast will be recorded and made available on the IMV website for 30 days following the call.

On June 4, 2019 Celgene Corporation (NASDAQ: CELG) reported that data from the TRANSCEND CLL 004 and TRANSCEND NHL 001 trials studying the investigational anti-CD19 chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (liso-cel; JCAR017) in patients with B-cell blood cancers were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago (Press release, Celgene, JUN 4, 2019, View Source [SID1234536877]).

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Updated results from the ongoing, open-label multicenter phase 1/2 TRANSCEND CLL 004 study (Abstract #7501) of liso-cel in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) were presented in an oral presentation today. The data included safety and efficacy findings from 23 patients who received liso-cel infusion at one of two dose levels: 50 × 106 or 100 × 106 total CAR-positive T cells following lymphodepleting chemotherapy. All patients had been previously treated with ibrutinib, and more than half had received prior venetoclax. The median number of lines of prior therapy was five and 83% of patients had high-risk cytogenetic features.

In the study, 22 of 23 patients were evaluable for response. The best overall response rate was 82% (18/22), with 46% (10/22) of patients achieving complete remission with or without complete blood count recovery (CR/CRi). Of 20 patients evaluable for minimal residual disease (MRD), 75% (15/20) achieved undetectable MRD (uMRD) by blood measures (sensitivity, 10-4) and 65% (13/20) achieved uMRD by bone marrow measures (sensitivity, 10-4). Responses have been durable, with 83% of patients (5/6) who were in CR/CRi at six months post liso-cel infusion showing ongoing response.

"For patients who have failed the current standard of care treatments for CLL, such as ibrutinib and venetoclax, there is a need for additional treatment options," said lead study investigator Tanya Siddiqi, M.D., City of Hope National Medical Center. "I am highly encouraged by this early data showing manageable toxicity and promising clinical activity in a heavily pretreated patient population with high-risk CLL. In this preliminary analysis, clinical responses are rapid, deep and durable when assessed by clinical and MRD criteria. We look forward to further investigation of liso-cel in CLL patients who have relapsed from or have become refractory to currently available treatment options."

The most common treatment-emergent adverse events (TEAEs) of any grade were anemia (83%), cytokine release syndrome (CRS; 74%), thrombocytopenia (74%), neutropenia (57%), and leukopenia (48%). There were two patients with dose-limiting toxicities among the 14 patients treated at 100 × 106 total CAR-positive T cells: grade 4 hypertension in one patient; and grade 3 encephalopathy, grade 3 muscle weakness and grade 4 tumor lysis syndrome in the other patient. Across 23 patients evaluable for safety, TEAEs of note included grade 3 CRS (2/23), grade ≥ 3 neurological events (5/23), and grade ≥ 3 tumor lysis syndrome (4/23). No grade 5 CRS or neurological events occurred.

In addition to these findings from TRANSCEND CLL 004, preliminary safety and efficacy data were presented from two subgroup analyses from the ongoing, open-label multicenter phase 1 TRANSCEND NHL 001 trial evaluating liso-cel in patients with R/R B-cell non-Hodgkin’s lymphoma at one of two dose levels: 50 × 106 or 100 × 106 total CAR-positive T cells following lymphodepleting chemotherapy. The data included results from a subgroup of patients with secondary central nervous system (CNS) lymphoma (n=9) (Abstract #7515) and from patients with R/R mantle cell lymphoma (MCL; n=17) (Abstract #7516). These were highlighted in a poster discussion session on Monday, June 3.

Patients had secondary CNS lymphoma at the time of first treatment (n=7; 6 DLBCL, 1 MCL) or retreatment with liso-cel (n=2 DLBCL), and neurological events and CRS were observed in only one patient. Of the 6 DLBCL patients with CNS lymphoma at the time of first retreatment with liso-cel, 4 achieved complete responses, 2 of whom are in sustained remission at more than 8 and 17 months, respectively.

The data in patients with MCL included safety and preliminary efficacy findings for 17 treated patients. The most common grade ≥ 3 TEAEs were thrombocytopenia (41%), anemia (35%) and neutropenia (35%). Grade ≥ 3 CRS and neurological events occurred in 6% and 12% of patients, respectively. One fatal event of tumor lysis syndrome was observed. The best overall response rate across dose levels was 71% (12/17); the best complete response rate was 53% (9/17). These results are consistent with those seen in all patients treated with liso-cel in the TRANSCEND NHL 001 study.

"We are pleased to share these new data, which continue to demonstrate the potential of liso-cel in a range of B-cell cancers, at this year’s ASCO (Free ASCO Whitepaper)," said Alise Reicin, M.D., President, Global Clinical Development at Celgene. "These results support our continued commitment to broadly develop CAR T-cell therapies to address the clinical needs of patients living with blood cancers."

Liso-cel is not approved in any country.

About Liso-cel

Liso-cel is an investigational defined composition CD19-directed CAR T-cell product candidate using a 4-1BB costimulatory domain. Celgene’s lead CAR T trial, TRANSCEND NHL-001, is studying liso-cel in adult patients with relapsed or refractory diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, follicular lymphoma Grade 3B and mantle cell lymphoma.

About Celgene’s Cell Therapies

Celgene is committed to advancing the field of immune cell therapy – from pursuing scientific breakthroughs to enabling routine clinical use – so that more patients may benefit from the research that may ultimately lead to these emerging treatments. Celgene is building a portfolio of cell therapies supported by more than 15 years of development, including several chimeric antigen receptor (CAR) T-cell agents in registrational trials across multiple disease states, and a growing early-stage pipeline that expands cell therapy targets and technologies. We are advancing cell therapies in diffuse large B-cell lymphoma, multiple myeloma and other B-cell malignancies. These efforts underscore our belief in the promise of cell therapy to redefine the way patients fight cancer and to potentially transform how these diseases are treated.

On June 4, 2019 Myovant Sciences (NYSE: MYOV), a clinical-stage healthcare company focused on developing and commercializing innovative therapies for women’s health and prostate cancer, reported that Lynn Seely, M.D., President and Chief Executive Officer, will present at the following investor conferences (Press release, Myovant Sciences, JUN 4, 2019, https://investors.myovant.com/news-releases/news-release-details/myovant-sciences-present-upcoming-june-investor-conferences [SID1234536876]):

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Annual Roivant Pipeline Day in New York, NY on Thursday, June 6, 2019 at 3:20 p.m. ET

Goldman Sachs 40th Annual Global Healthcare Conference in Rancho Palos Verdes, CA on June 11, 2019 at 2:40 p.m. PT
A live webcast of each event will be accessible on the Events page under the Investors and Media section of the Myovant website at www.myovant.com. Please connect to the company’s website at least 15 minutes prior to the presentation to ensure adequate time for any software download that may be required to listen to the webcast. A replay of the webcast will be available at the same location for 30 days following the conference.