On June 3, 2017 Bristol-Myers Squibb Company (NYSE:BMY) and QIAGEN (NASDAQ:QGEN; Frankfurt Prime Standard:QIA) reported that they have signed an agreement to explore the use of next-generation sequencing (NGS) technology to develop gene expression profiles (GEPs) as predictive or prognostic tools for use with Bristol-Myers Squibb novel immuno-oncology (I-O) therapies in cancer treatment (Press release, Bristol-Myers Squibb, JUN 3, 2017, View Source [SID1234519383]). This will leverage the combination of Bristol-Myers Squibb’s portfolio of I-O therapies with QIAGEN’s proven track record in developing and commercializing companion and complementary diagnostics as well as QIAGEN’s portfolio of NGS technologies. I-O therapies offer a novel way to treat cancer by using drugs to target the body’s immune system to help fight cancer.

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QIAGEN and Bristol-Myers Squibb intend to develop GEPs for several Bristol-Myers Squibb I-O molecules under the initial agreement. The companies also plan to enter into a further agreement to develop diagnostic products using the jointly developed GEPs and to expand the use of NGS technology with other Bristol-Myers Squibb I-O therapies.

"Greater precision in the treatment of cancer may enable faster decision making to identify which patient populations are most likely to derive benefit from our immuno-oncology agents," said Fouad Namouni, M.D., head of Development, Oncology, Bristol-Myers Squibb. "We believe working with QIAGEN will help develop better diagnostic tools to target the most appropriate immunotherapies across a number of different tumor types."

"We are very pleased to work with Bristol-Myers Squibb to potentially create what could be the first-ever NGS-based companion or complementary diagnostic to provide key insights for personalized decision-making in the rapidly expanding area of immuno-oncology," said Peer M. Schatz, Chief Executive Officer of QIAGEN. "Our teams at QIAGEN are looking forward to working with Bristol-Myers Squibb to leverage the power of NGS technology to potentially improve outcomes for patients."

QIAGEN and Bristol-Myers Squibb have been partnering since 2009. A key milestone in this partnership was the FDA approval of the Therascreen KRAS companion/complementary diagnostic assay in 2012.

Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research

At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines for hard-to-treat cancers that could potentially improve outcomes for these patients.

We are leading the scientific understanding of I-O through our extensive portfolio of investigational compounds and approved agents. Our differentiated clinical development program is studying broad patient populations across more than 50 types of cancers with 14 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs position us to advance I-O/I-O, I-O/chemotherapy, I-O/targeted therapies and I-O/radiation therapies across multiple tumors and potentially deliver the next wave of therapies with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and how patients’ individual tumor biology can be used as a guide for treatment decisions throughout their journey.

We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.

QIAGEN GeneReader NGS System

The GeneReader NGS System provides the first true Sample to Insight NGS workflow for laboratories worldwide – and increasingly also pharmaceutical companies – to take advantage of the power of NGS technology. The system’s integrated bioinformatics for analysis and interpretation of NGS data, as well as a family of gene panels under the GeneRead QIAact brand, enable laboratories to identify gene variations linked to cancers and to deliver actionable molecular insights. The capabilities of this unique system also include high-sensitivity detection in liquid biopsy samples, compatibility with the QIAsymphony automation platform for high-throughput sample processing, and software integration with leading Laboratory Information Management Systems (LIMS). The current version of the GeneReader NGS System is available in the United States for research use only.

On June 3, 2017 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported the online publication of a new research brief in Cancer Discovery outlining the preclinical rationale for LOXO-195 and clinical proof-of-concept data from the first two patients treated (Press release, Loxo Oncology, JUN 3, 2017, View Source [SID1234519387]). LOXO-195 was developed to treat patients with TRK fusion cancers who become resistant while receiving another TRK inhibitor, such as Loxo Oncology’s larotrectinib.

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"This publication highlights the potential for LOXO-195 to extend the period of durable disease control for patients with TRK fusion cancers," said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. "We believe that today’s ASCO (Free ASCO Whitepaper) presentation establishes larotrectinib as the clear first choice for patients with TRK fusion cancers. However, over time, patients will require new treatment options, since oncogene-addicted metastatic cancers ultimately evade targeted therapies. We have been relentless in the development of LOXO-195 so that it could be ready in time for the current larotrectinib clinical trial participants and future patients who depend upon us to realize the full potential of TRK inhibition in the management of advanced cancer."

LOXO-195 was designed to address anticipated mechanisms of acquired resistance in cancers exposed to a prior TRK inhibitor, including "solvent front" mutations (e.g. NTRK1 G595R, NTRK3 G623R), which are not well-addressed by existing investigational agents. LOXO-195 will be developed as a sequential treatment, to follow larotrectinib or another TRK inhibitor, to extend the total time of benefit from TRK inhibition.

The Cancer Discovery research brief provides early but encouraging evidence that the sequential use of larotrectinib followed by LOXO-195 could extend the total duration of disease control for patients with TRK fusion cancers. An analogous paradigm has already been established for other oncogene-addicted tumors, such as those driven by androgen and estrogen signaling, EGFR mutations and ABL gene fusions. The brief describes the first two patients with TRK fusion cancers who responded to larotrectinib but later relapsed. An adult with colorectal cancer and a child with infantile fibrosarcoma were biopsied at the time of tumor progression and found to have a solvent front TRK mutation in the existing TRK fusion, which explained the diminished activity of larotrectinib. As no other treatment options exist to address TRK fusion solvent front mutations, Loxo Oncology, in collaboration with the U.S. FDA, enabled these patients to access LOXO-195 through emergency use Investigational New Drug applications (INDs). Both patients responded to LOXO-195, with minimal adverse events reported.

A formal LOXO-195 IND was recently cleared by the U.S. FDA, and a Phase 1/2 trial is opening globally.

About LOXO-195
LOXO-195 is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that have acquired resistance to initial TRK therapy such as larotrectinib. Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. Though drugs such as larotrectinib can induce durable responses in these patients, the cancer may eventually begin to grow again. This phenomenon is called "acquired resistance," in that the cancer has acquired features conferring resistance to the initial therapy that was once effective. Emerging data in the field of TRK inhibition suggest that acquired resistance may emerge due to TRK kinase point mutations, such as those in the solvent front domain, xDFG domain, or gatekeeper region. LOXO-195 was designed to address these new point mutations and induce a new response in the patient’s cancer. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123 or email [email protected].

About TRK Fusion Cancer
TRK fusions are chromosomal abnormalities that occur when one of the NTRK genes (NTRK1, NTRK2, NTRK3) becomes abnormally connected to another, unrelated gene (e.g. ETV6, LMNA, TPM3). This abnormality results in uncontrolled TRK signaling that can lead to cancer. TRK fusions occur rarely but broadly in various adult and pediatric solid tumors, including appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, GIST, infantile fibrosarcoma, lung cancer, mammary analogue secretory carcinoma of the salivary gland, melanoma, pancreatic cancer, thyroid cancer, and various sarcomas. TRK fusions can be identified through various diagnostic tests, including targeted next-generation sequencing (NGS), immunohistochemistry (IHC), polymerase chain reaction (PCR), and fluorescent in situ hybridization (FISH). For more information, please visit www.TRKtesting.com.

On June 2, 2017 Dynavax Technologies Corporation (NASDAQ: DVAX) reported the presentation of findings in patients with metastatic melanoma in the dose escalation phase of an ongoing Phase 1b/2 study investigating SD-101, Dynavax’s intratumoral TLR9 agonist, in combination with KEYTRUDA (pembrolizumab), an anti-PD-1 therapy developed by Merck, known as MSD outside the United States and Canada (Press release, Dynavax Technologies, JUN 2, 2017, View Source [SID1234519437]). Results evaluating 19 patients for efficacy and 22 patients for safety were presented in a poster at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago:

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• In 7 anti-PD-1/L1-naïve patients, SD-101 used in combination with KEYTRUDA resulted in an overall response rate (ORR) of 100%, with a complete response (CR) rate of 29%. This is a meaningful increase over use of KEYTRUDA alone, which has already shown a 33% ORR, with a 6% CR.1

• In 12 patients with advanced (stage IIIc/IV) melanoma who had previously failed on anti-PD-1 treatment, introduction of SD-101 resulted in tumor shrinkage in 42% of patients, with 17% having a partial response (PR), indicating an anti-tumor immune response generated by SD-101.

• The combination of SD-101 and KEYTRUDA in this study, mobilized both innate and adaptive immune response in study participants.

• Tumor shrinkage was observed in non-injected visceral lesions.

"Having 7 out of 7 patients naïve to anti-PD-1/L1 treatment responding is very encouraging," said Antoni Ribas, M.D., Ph.D., of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, and lead investigator. "These results are supported by tumor shrinkage in patients who had previously progressed on anti-PD-1 treatment and by confirmatory laboratory biomarker assessments in tumor biopsies. If these clinical results are sustained in the ongoing trial, this combination, which mobilizes both innate and adaptive immune responses in patients, could represent an important advancement in immuno-oncology."

SD-101 in combination with KEYTRUDA generally was well-tolerated. No dose-limiting toxicities of the combination were observed in any dose cohort, and a maximum tolerated dose (MTD) was not identified. The most common treatment-emergent adverse events were injection site reactions and transient grade 1 to 2 flu-like symptoms, including fever, chills and myalgia. The study also includes biomarker assessments, suggesting that treatment with SD-101 and KEYTRUDA resulted in increased tumor-infiltrating lymphocytes and decreased Th2 in tumor biopsies, consistent with induction of an antitumor immune response.

Keytruda.com View Source

About MEL-01 (KEYNOTE-184)
The dose-escalation and expansion study of SD-101 in combination with KEYTRUDA includes patients with histologically or cytologically confirmed unresectable Stage IIIc/IV melanoma. The primary endpoints of the trial are MTD and evaluation of the safety of intratumoral SD-101 in combination with KEYTRUDA. In addition, the trial is investigating response as assessed by the investigator according to RECIST v1.1, biomarker assessments and duration of response. Patients previously treated with anti-PD-1 and other immunotherapies are included.

About SD-101
SD-101 is Dynavax’s proprietary, second-generation, Toll-like receptor 9 (TLR9) agonist CpG-C class oligodeoxynucleotide. SD-101 is being studied for its multiple anti-tumor activities in innate immune cells and activation of plasmacytoid dendritic cells to stimulate T cells specific for antigens released from dying tumor cells. TLR9 agonists such as SD-101 enhance T and B cell responses and provide potent Type 1 interferon induction and maturation of plasmacytoid dendritic cells to antigen-presenting cells. SD-101 is being evaluated in several Phase 1/2 oncology studies to assess its safety and activity.

For information about SD-101 trials that are currently recruiting patients, please visit www.clinicaltrials.gov.

On June 2, 2017 (GLOBE NEWSWIRE) — TG Therapeutics, Inc. (NASDAQ:TGTX) reported the schedule of presentations featuring TG-1101 and TGR-1202 at the upcoming 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), being held this week, June 2 – 6, 2017, at McCormick Place in Chicago, Illinois (Press release, TG Therapeutics, JUN 2, 2017, View Source [SID1234519352]).

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Latest on Cancer Drug Development at ASCO (Free ASCO Whitepaper), book your free 1stOncology demo here.

Oral Presentation:

Title: Ublituximab and ibrutinib for previously treated genetically high-risk chronic lymphocytic leukemia: Results of the GENUINE Phase 3 study
– Abstract Number: 7504
– Date & Time: Saturday, June 3, 2017 3:00 PM – 6:00 PM CT
– Presentation Time: 4:12 PM CT
– Session Title: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
– Presenter: Jeffrey P. Sharman, MD

Poster Discussion Presentation:

Title: Tolerability and activity of chemo-free triplet combination of TGR-1202, ublituximab, and ibrutinib in patients with advanced CLL and NHL
– Abstract Number: 7511
– Presentation Date & Time: Monday, June 5, 2017 8:00 AM-11:30 AM CT (Poster Viewing); 1:15 PM-2:30 PM CT (Poster Discussion)
– Session Title: Poster Discussion Session, Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
– Presenter: Loretta Nastoupil, MD

Trials in Progress Poster Presentation:

Title: 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 Number: TPS7569
– Presentation Date & Time: Monday, June 5, 2017 8:00 AM-11:30 AM CT
– Session Title: Poster Session, Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
– Presenter: Colleen Dorsey, BSN, RN

Abstracts are available online and can be accessed at www.asco.org. Following each presentation, the data presented will be available on the Publications page, located within the Pipeline section, of the Company’s website at www.tgtherapeutics.com.

TG THERAPEUTICS INVESTOR & ANALYST EVENT

TG Therapeutics will host a reception on Monday, June 5, 2017 beginning at 7:00pm CT, with featured presentations now beginning promptly at 7:05pm CT. The event will take place at the Peninsula Chicago Hotel in the Avenues Ballroom. This event will be webcast live and will be available on the Events page, located within the Investors & Media section of the Company’s website at www.tgtherapeutics.com, as well as archived for future review. This event will also be broadcast via conference call. To access the conference line, please call 1-877-407-8029 (U.S.), 1-201-689-8029 (outside the U.S.), and reference Conference Title: TG Therapeutics June 2017 Investor & Analyst Event.

On June 2, 2017 NewLink Genetics Corporation (NASDAQ:NLNK) reported the results from a Phase 2 trial of indoximod in combination with taxane chemotherapy for patients with metastatic breast cancer (Press release, NewLink Genetics, JUN 2, 2017, View Source [SID1234519388]).

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Top line data from the study show that the trial did not meet its pre-specified endpoints of a statistically significant difference between the two treatment groups as to progression-free survival, overall survival or objective response rate.

"As demonstrated by multiple studies that have been reported since the start of this clinical trial, breast cancer unfortunately remains a challenging disease in immuno-oncology," said Primary Investigator Hatem Soliman MD, Associate Member Breast, Tumor Biology, and Immunology Departments, Chair Clinical Research Advisory Committee, H. Lee Moffitt Cancer Center and Research Institute, Associate Professor, Division of Oncologic Sciences University of South Florida.

In this study, NLG2101, 169 first line metastatic breast cancer patients were selected to receive either docetaxel or paclitaxel by their treating physicians. Once the choice of backbone chemotherapy was made, patients were then randomized to receive either indoximod or placebo.

"We would like to thank all the patients, families, investigators, and research teams who supported the completion of this trial," said Charles J. Link, Jr., M.D., Chairman and CEO of NewLink Genetics. "Independent of these results, we continue to be highly encouraged by indoximod as an IDO pathway inhibitor and look forward to future opportunities to share data from ongoing trials in multiple cancer types including melanoma, prostate cancer, acute myelogenous leukemia, and pancreatic cancer."

Full results of the trial will be presented at an upcoming academic meeting.