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Sierra Reports Late-Breaking Preclinical Data for SRA737 Presented at AACR 2019

On April 1, 2019 Sierra Oncology, Inc. (Nasdaq: SRRA), a clinical stage drug development company focused on advancing targeted therapeutics for the treatment of patients with significant unmet needs in hematology and oncology, reported that preclinical data for SRA737+LDG, its Chk1 inhibitor plus non-cytotoxic low dose gemcitabine (LDG), in combination with immunotherapy, are being reported today in a late-breaking oral presentation at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 being held in Atlanta, Georgia (Press release, Sierra Oncology, APR 1, 2019, View Source [SID1234534861]).

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"Given the limited response rates for anti-PD-L1 drugs in patients with small cell lung cancer (SCLC), better treatment options are sorely needed. Our data, showing durable tumor regressions when combining SRA737+LDG with anti-PD-L1 in a mouse model, warrant further clinical studies to investigate the potential of this approach as a strategy to improve outcomes in our patients," said senior researcher Lauren Averett Byers, M.D., Associate Professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, Houston, Texas.

In the study, SRA737+LDG demonstrated significant anti-tumor activity when combined with anti-PD-L1 in a mouse model of SCLC, resulting in durable tumor regressions. These results were accompanied by an induction of anti-tumor cytotoxic T-cells and M1 macrophages and a corresponding reduction in several pro-tumorigenic cell types in the tumors of drug-treated animals.

"The unique replication stress-inducing properties of SRA737 as potentiated by non-cytotoxic low dose gemcitabine have been previously demonstrated to result in intrinsic anti-tumor activity in multiple preclinical models. These striking new data provide evidence for SRA737+LDG’s activation of innate immune signaling and the establishment of an anti-tumor immune microenvironment that synergizes with immune checkpoint inhibitors," said Dr. Christian Hassig, Chief Scientific Officer, Sierra Oncology. "These findings provide a mechanistic basis for the growing body of evidence highlighting a synergistic interplay between replication stress and anti-tumor immune responses and afford a compelling rationale for evaluating SRA737+LDG with immunotherapy in the clinic."

SRA737 AACR (Free AACR Whitepaper) Late-Breaking Oral Presentation:
Date/Time: Monday, April 1st from 3:00 to 5:00 pm ET
Session: Minisymposium: Late-Breaking Research 2
Title: Combination treatment of the CHK1 inhibitor, SRA737, and low dose gemcitabine demonstrates profound synergy with anti-PD-L1 inducing durable tumor regressions and modulating the immune microenvironment in small cell lung cancer
Authors: Triparna Sen, Carminia M. Della Corte, Snezana Milutinovic, Lixia Diao, Robert J Cardnell, Ryan J. Hansen, Bryan Strouse, Michael P. Hedrick, Christian Hassig, Jing Wang, Lauren A Byers.
Location: Georgia World Congress Center, Room B404

Summary slides from this presentation will be made available on the company’s website at www.sierraoncology.com

About SRA737+LDG
SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1), a key regulator of cell cycle progression and the DNA Damage Response (DDR). SRA737+LDG is a novel drug combination, where non-cytotoxic low dose gemcitabine acts as a potent inducer of replication stress that potentiates SRA737’s anti-tumor activity.

Phase 1/2 clinical trials of SRA737 as monotherapy (NCT02797964) and in combination with low dose gemcitabine (NCT02797977) in multiple solid tumors (ovarian, prostate, non-small cell lung, squamous (head & neck, anal), colorectal, small cell lung, sarcoma, cervical, anogenital) are ongoing. Sierra has also prepared for a potential clinical study of SRA737 in combination with a PARP inhibitor.

Sierra Oncology retains the global commercialization rights to SRA737.

Vaccibody AS and Nektar Therapeutics Present New Preclinical Data from their Immuno-Oncology Collaboration at the American Association for Cancer Research (AACR) Annual Meeting 2019

On April 1, 2019 Vaccibody AS and Nektar Therapeutics (Nasdaq: NKTR) reported the presentation of new preclinical data for VB10.NEO, a personalized neoantigen cancer vaccine, combined with bempegaldesleukin (NKTR-214 or bempeg), a CD122-preferential IL-2 pathway agonist (Press release, Vaccibody, APR 1, 2019, View Source [SID1234534860]). These data were presented today in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019.

"We are excited to present these novel preclinical data that show combining bempeg with VB10.NEO synergize to increase both the breadth and the depth of the neoantigen-specific immune response. These unique and non-overlapping mechanisms produced an expansion of the VB10.NEO elicited neoantigen-specific T cells and demonstrated enhanced anti-tumor efficacy in mice. We look forward to evaluating this novel immuno-oncology combination in a clinical study in patients with advanced or metastatic squamous cell carcinoma of head and neck later this year," said Agnete B. Fredriksen, Ph.D., Vaccibody’s President and Chief Scientific Officer.

VB10.NEO is designed to specifically activate a patient’s immune system to tumor-specific antigens, called neoantigens. Bempeg is designed to expand and proliferate tumor antigen-specific T cells in the tumor microenvironment. Addition of bempeg to VB10.NEO is intended to drive maximal expansion of vaccine-induced neoantigen-specific T cells for the treatment of cancer.

"Personalized T cell vaccines could play a critical and central role in cancer immunotherapy," said Jonathan Zalevsky, Ph.D., Chief Scientific Officer at Nektar. "These preclinical data highlight the potential of combining a personalized cancer vaccine with a T cell proliferator to induce maximal expansion of vaccine-induced T cell clones and durable responses and specific anti-tumor immunity. We are highly encouraged by these results and look forward to testing this unique approach to personalized cancer treatment in patients with squamous cell carcinoma of the head and neck."

Details of the poster presentation at AACR (Free AACR Whitepaper) are as follows and will be available for download at the time of presentation at View Source and View Source

Abstract #2256
Title: "Combination of neoantigen DNA plasmid vaccine VB10.NEO and NKTR-214, a CD122-biased immunostimulatory cytokine, induces strong neoantigen-specific T cell responses and sustained tumor regression in pre-clinical models"
Session: Clinical Research – Combination Therapies 1
Session Data and Time: Monday, April 1, 2019, 1:00 p.m. – 5:00 p.m. Eastern Time

Combination of VB10.NEO and NKTR-214 synergizes to elicit greater breadth and depth of neoantigen-specific T cell responses than each individual treatment.
The synergistic effect was observed in both CD4 and CD8 T cells, and most pronounced on CD8 T cell responses, further supporting the combination’s potential to induce strong immunogenic CD8+ T cell responses.
VB10.NEO in combination with NKTR-214 and anti-PD-1 induce rapid, complete and durable tumor regression of small tumors and long-lasting stabilization of large tumors supporting the rationale for examining the combination clinically.
In September 2018, Nektar and Vaccibody entered into a clinical collaboration to evaluate bempegaldesleukin in combination with VB10.NEO. A pilot study evaluating the combination in patients with squamous cell carcinoma of the head and neck is planned to begin mid-2019.

About VB10.NEO
VB10.NEO, is a proprietary therapeutic DNA vaccine which uses the patient’s own neoantigens for the personalized treatment of cancer patients. A phase I/IIa neoantigen clinical trial is currently enrolling patients with locally advanced or metastatic melanoma, non-small cell lung carcinoma, clear renal cell carcinoma as well as urothelial cancer or squamous cell carcinoma of the head and neck.

About bempegaldesleukin (NKTR-214)
Bempegaldesleukin is an investigational, first-in-class, CD122-preferential IL-2 pathway agonist designed to provide rapid activation and proliferation of cancer-killing immune cells, known as CD8+ effector T cells and natural killer (NK) cells, without over activating the immune system. Bempegaldesleukin stimulates these cancer-killing immune cells in the body by targeting CD122 receptors found on the surface of these immune cells. CD122, which is also known as the Interleukin-2 receptor beta subunit, is a key signaling receptor that is known to increase proliferation of these effector T cells.1 In clinical and preclinical studies, treatment with bempegaldesleukin resulted in expansion of these cells and mobilization into the tumor micro-environment.2,3 Bempegaldesleukin has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines.

Mirati Therapeutics To Present At The H.C. Wainwright & Co. Global Life Sciences Conference

On April 1, 2019 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical stage targeted oncology company, reported that it will present at the H.C. Wainwright & Co. Global Life Sciences Conference in London, England on Monday, April 8th at 11:30am BST/6:30am ET/3:30am PT. Christopher C. LeMasters, Chief Business Officer, will provide a corporate update at the conference (Press release, Mirati, APR 1, 2019, Mirati Therapeutics To Present At The H.C. Wainwright & Co. Global Life Sciences Conference [SID1234534859]).

The presentations will be webcast and made available through the "Investors" section of www.mirati.com, and replays will be made available for 90 days following the events.

Sangamo Therapeutics To Host April 2, 2019 Conference Call To Provide Clinical Update

On April 1, 2019 Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, reported that management will host a conference call on Tuesday, April 2nd at 8:00 a.m. Eastern Time to provide a clinical development update (Press release, Sangamo Therapeutics, APR 1, 2019, View Source [SID1234534858]).

The conference call will be webcast live and can be accessed via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations.

The conference call dial-in numbers are (877) 377-7553 for domestic callers and (678) 894-3968 for international callers. The conference ID number for the call is 6063108. For those unable to listen in at the designated time, a conference call replay will be available for one week following the call. The conference call replay numbers for domestic and international callers are (855) 859-2056 and (404) 537-3406, respectively. The conference ID number for the replay is 6063108.

Resolution Liquid Biopsy Assay Outperforms Guardant360 in Retrospective Non-Small Cell Lung Carcinoma Comparison Pilot Study

On April 1, 2019 Resolution Bioscience, Inc. reported that scientists from Dana-Farber Cancer Institute are presenting the results of a retrospective liquid biopsy comparison study between Resolution’s ctDx-Lung assay and Guardant Health’s Guardant360 test this morning at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Resolution Bioscience, APR 1, 2019, View Source [SID1234534857]).

Liquid biopsy assays have the potential to expand access to personalized care for those whose tissue biopsies are inadequate or unavailable and may present an opportunity for enhanced cancer monitoring and detection of minimal residual disease. The study was conducted to explore the technical differences and test the reliability of cell-free DNA next-generation sequencing (NGS) assays, which are not completely characterized at this time.

The comparison study highlights detection challenges of complex mutations such as gene fusions, as well as the need for platform cross-comparisons to realize the potential of liquid biopsy and increase access to personalized cancer care. A cohort of 169 non-small cell lung cancer (NSCLC) patients with Guardant360 results were screened for gene fusions. The team of scientists at Dana-Farber used a soon-to-be-released ctDx-Lung kit to analyze 16 cases that had a rearrangement in their tumor, along with additional banked plasma. All personnel involved in sample analysis were blinded to tumor genotype and Guardant360 results. The team found that the Resolution ctDx-Lung assay identified more actionable gene fusion mutations with higher allele frequencies than the Guardant360 test. The results further demonstrate the potential of the ctDx-Lung kit for patients with advanced NSCLC.

The ctDx-lung kit detected 13 out 16 fusions (allele frequency range 80-0.3%), while Guardant360 detected only seven (allele frequency range 10-0.3%). Of the 13 cases where an oncogenic fusion was detected in plasma, 89% of patients with productive fusions and 75% of patients with ‘non-productive’ fusions responded to tyrosine kinase inhibitor (TKI) therapies. Additional unblinding is ongoing to better understand false negative cases.

"This study is another strong validation of our targeted NGS-based liquid biopsy platform and its ability to outperform other assays, such as the Guardant360 test," said Mark Li, CEO of Resolution Bioscience. "These results prove our kits can be run at the leading cancer centers around the world, enabling more scientists to detect more of these actionable mutations, which will soon transform the way we diagnose, treat and monitor devastating diseases like NSCLC."

Attendees interested in the presentation, "Building an effective concordance study: Plasma Next Generation Sequencing (NGS) for oncogenic fusion detection in non-small cell lung carcinoma (NSCLC)," by Cloud Paweletz, PhD, of the Belfer Center at Dana-Farber Cancer Institute can reference abstract 1374/13. The study is being presented today between 8 AM-12 PM in Section 19 of the Georgia World Congress Center Exhibit Hall.

The funding for the study was provided by the Expect Miracles Foundation, the Robert and Renee Belfer Foundation, the Damon Runyon Cancer Research Foundation, and the Harold and Gail Kirstein Lung Cancer Research Fund.

To view the scientific poster, please visit www.resolutionbio.com/publications/AACR2019_DFCI_Fusions.pdf.

About Resolution ctDx-Lung

ctDx-Lung is built on Resolution’s patented cell-free DNA NGS analysis platform. The liquid biopsy assay captures and analyzes circulating tumor DNA (ctDNA) for driver mutations in 20 genes associated with NSCLC using Resolution’s proprietary targeted capture NGS chemistry and cloud-based bioinformatics.