NantKwest, NantCell and NantOmics to Provide Updated Preclinical and Clinical Data in Four Abstracts at Part of the American Society of Clinical Oncology Annual Meeting
Preclinical and Clinical Data Demonstrate Advanced Deployment of Precision Medicine Tools to Analyze and Potentially More Effectively Intervene with Highly Focused Therapeutic Interventions
Dr.
Abstract Title: Innate and adaptive immunotherapy: An orchestration of immunogenic cell death by overcoming immune suppression and activating NK and T-cell therapy in patients with third line or greater Triple-Negative Breast Cancer (TNBC).
Sub-category: Triple-Negative
Category: Breast Cancer—Metastatic
Meeting: 2019 ASCO Annual Meeting
Abstract Number: e12566
Citation: J Clin Oncol 37, 2019 (suppl; abstr e12566)
Author(s):
Summary: Triple-negative breast cancer (TNBC) is a heterogenous subtype of breast cancer that is frequently aggressive and has limited treatment options. We hypothesize that effective and sustained response against TNBC requires a coordinated approach that: (1) reverses the immune-suppressive tumor microenvironment, (2) induces immunogenic tumor cell death and (3) Re-engages NK and T-cell tumor response against a cascade of tumor antigens. To test this hypothesis, we have developed a temporospatial approach that combines metronomic low dose chemotherapy, SBRT, off-the-shelf cryopreserved allogeneic NK cells, yeast and adenoviral tumor-associated antigen vaccines, an IL-15RαFc superagonist, and checkpoint inhibition. Methods: A phase 1b trial in patients with previously-treated metastatic TNBC was initiated. Treatment occurred in 3-week cycles of low-dose chemotherapy (aldoxorubicin, cyclophosphamide, cisplatin, nab-paclitaxel, 5-FU/L), antiangiogenic therapy (bevacizumab), SBRT, engineered allogeneic CD16 NK-92 cells (haNK), IL-15RαFc (N-803), adenoviral vector-based CEA, MUC1, brachyury, and HER2 vaccines, yeast vector-based Ras, brachyury and CEA vaccines, and an IgG1 PD-L1 inhibitor, avelumab. The primary endpoint is incidence of treatment-related adverse events (TRAEs). Secondary endpoints include ORR, DCR, PFS, and OS. Preliminary results reported on 8 subjects treated with 3rd-line or greater TNBC that have received at least 3 treatment cycles (mean = 6 cycles). All treatment was administered in an outpatient setting. All subjects had at least 1 grade ≥3 TRAE, primarily chemotherapy-related neutropenia. Grade ≥3 haNK-related AEs (fever and fatigue) were observed in 2 subjects. 2 subjects experienced SAEs. 7 subjects remain alive, with 6 subjects receiving ongoing study treatment. 1 CR (confirmed) and 2 PRs (one confirmed) have been observed to date. These preliminary data suggest that low-dose chemo-radiation combined with innate and adaptive immunotherapy can be administered safely in an outpatient setting with a manageable safety profile. Clinical trial information: NCT03387085.
Abstract Title: Innate and adaptive immunotherapy: An orchestration of immunogenic cell death by overcoming immune suppression and activating NK and T cell therapy in patients with third line or greater metastatic pancreatic cancer.
Sub-category: Pancreatic Cancer
Category: Gastrointestinal (Noncolorectal) Cancer
Meeting: 2019 ASCO Annual Meeting
Abstract Number: e15787
Citation: J Clin Oncol 37, 2019 (suppl; abstr e15787)
Author(s):
Summary:
Pancreatic cancer has multiple mechanisms to prevent immune recognition that lead to the creation of an immune suppressive tumor microenvironment. Our hypothesis is that sustained response against pancreatic cancer requires a coordinated approach that: (1) reverses the immune-suppressive tumor microenvironment, 2. induces immunogenic tumor cell death and (3) re-engages NK and T-cell tumor response against a cascade of tumor antigens. To test this hypothesis, we have developed a temporospatial approach that combines metronomic low-dose chemotherapy, SBRT, cryopreserved allogeneic NK cells, yeast and adenoviral tumor-associated antigen vaccines, an IL-15RαFc superagonist, and checkpoint inhibition. These preliminary data suggest that low-dose chemo-radiation combined with innate and adaptive immunotherapy can be administered safely in an outpatient setting.
Preliminary results of 12 subjects treated with 3rd-line or greater metastatic pancreatic cancer. All treatment was administered in an outpatient setting. AEs were primarily hematologic and managed by planned chemo dose reduction. Grade ≥3 TRAEs were observed in 9 out of 12 subjects, predominately chemotherapy-related neutropenia. 9 out of 12 subjects (75%) had a best response of stable disease (≥ 8 weeks). Median PFS is 7.1 months (4.4 – 8.8) and median OS is 8.2 months (5.7 – 9.7) with 1 subject continuing treatment
Preliminary Overall Survival of 8.2 months is encouraging for this heavily-pretreated population. Clinical trial information: NCT03586869.
Abstract Title: Correlation between circulating cell-free RNA biomarkers and response during combination immunotherapy in previously refractory metastatic TNBC patients.
Sub-category: Circulating Biomarkers
Category: Developmental Immunotherapy and Tumor Immunobiology
Meeting: 2019 ASCO Annual Meeting
Abstract No: e14027
Citation: J Clin Oncol 37, 2019 (suppl; abstr e14027)
Author(s):
Summary: A commercial liquid biopsy test was included as an exploratory component of an integrated immunotherapy clinical trial in previously refractory metastatic TNBC patients, combining innate, high-affinity natural killer cell (haNK) therapy with adenoviral and yeast-based vaccines and an IL-15 superagonist (NCT 03387085). The purpose of the study was to assess the utility of cell-free circulating RNA (cfRNA) as a predictor of treatment response. The amount and variability of cfRNA was found to be positively correlated with the tumor size. As cfRNA quantity and variability increased or decreased, a corresponding increase or decrease in tumor size was observed, respectively. Not all 18 genes showed consistent patterns of change across the six patients, however the average expression and variability of the 18 genes showed evidence of a correlation with tumor size change from baseline (p-values = 0.08 and 0.03, respectively). Only trace levels of PD-L1 expression were observed in all 6 patients at baseline, prior to the initiation of the combination immunotherapy. Among the 5 patients that showed a reduction in tumor size of at least 10%, 4 also showed an associated increase in cfRNA PD-L1 expression from nearly 0 to normalized values between 2.1 and 6.8. In an exploratory analysis in an ongoing combination immunotherapy clinical trial for TNBC showed that increasing and decreasing cfRNA levels are correlated with increasing and decreasing tumor size, respectively. Increased PD-L1 cfRNA levels are correlated with beneficial treatment response. Liquid biopsy of cfRNA could provide an effective biomarker of treatment response. Clinical trial information: NCT03387085.
Abstract Title: TCR repertoire analysis from peripheral blood for prognostic assessment of patients during treatment
Sub-category: Circulating Biomarkers
Category: Developmental Immunotherapy and Tumor Immunobiology
Meeting: 2019 ASCO Annual Meeting
Abstract Number: e14040
Citation:J Clin Oncol 37, 2019 (suppl; abstr e14040)
Author(s): Sadanand Vodala,
Summary:
Immune checkpoint inhibitor therapy offers substantial clinical advantage to a subset of patients but predictive/novel prognostic indicators are still scarce. T cell receptors (TCRs) play a crucial role in adaptive immunity and anti-tumor immune responses. Net diversity of TCR repertoires are altered in patients receiving immune checkpoint inhibitors. To study the prognostic significance of T cell repertoires as a biomarker of immune responses in cancer patients, TCR repertoires were characterized from peripheral blood using high throughput sequencing. Patients that show positive response had TCR clones that were stable, which may indicate an existing immune related response towards their tumor. TCR-targeted therapy potentially allows these existing T-cells to overcome blockade by tumor cells. Patients showing poor response show a TCR repertoire that is constantly changing potentially indicating that the tumor cells are not eliciting a strong T cell specific response. Further functional studies of T cell populations are planned to expand our understanding of T cell based immune therapies.
For additional information, please visit www.nantkwest, www.nantcell.com, and www.nantomics.
About
With the capacity to grow active killer cells as a living cancer therapy, our NK cells have been designed to induce cell death against cancers and virally infected cells by several mechanisms, including: (i) innate killing, whereby all of our NK platforms recognize the stress proteins typically found on cancer cells, which, upon binding, release toxic granules to immediately kill their targets; (ii) antibody-mediated killing with our haNK® platform, which are NK cells engineered to express antibody receptors that can bind to therapeutic antibody products, thereby enhancing the cancer cell killing effect of that antibody; and (iii) Chimeric Antigen Receptor directed killing using the taNK® platform, which includes NK cells engineered to incorporate chimeric antigen receptors (CARs) to target tumor-specific antigens found on the surface of cancer cells. All three modes of killing (innate, antibody-mediated, and CAR directed killing) are employed by our t-haNK™ platform, which is an innovative combination of our aNK, haNK® and taNK® platforms in a single product.
Our haNK®, and t-haNK™ platforms have been designed to address certain
limitations of CAR T-cell therapy including the capability to infuse
cell therapy in an outpatient setting which allows for potential
reduction of risk for serious cytokine storms and protracted serious
adverse events. In Phase I and II clinical trials in patients with late
stage cancer, our NK cells have been administered as an investigational
outpatient infusion safely with greater than 300 infusions to date at a
dose of 2 billion cells per infusion. By leveraging an integrated
and extensive genomics and transcriptomics discovery and development
engine, together with a pipeline of multiple, clinical-stage,
immuno-oncology programs, we believe
For more information please visit www.nantkwest.com
Forward-Looking Statements
This press release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995.
Forward-looking statements include statements concerning or implying
that
Forward-looking statements are based on management's current expectations and are subject to various risks and uncertainties that could cause actual results to differ materially and adversely from those expressed or implied by such forward-looking statements. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements.
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detail in its
About NantCell
NantCell is a privately held immunotherapy company with one of the broadest portfolios of biological molecules spanning albumin-linked chemotherapeutic, peptide, fusion protein, cytokine, monoclonal antibody, adenovirus and yeast vaccine therapies.
This platform of technologies has enabled NantCell to achieve one of the most comprehensive late stage clinical pipelines addressing both the innate (activated macrophage and natural killer cell) and the adaptive immune system (dendritic, CD4 and CD8 killer T cells). The pipeline constitutes over 40 immunological assets with 13 first in human immunotherapy molecules in active clinical trials. In 2019, NantCell is planning the enrollment of patients in late stage trials with 3 molecules across 17 indications in solid and liquid tumors.
In the field of oncology, NantCell’s goal is to employ a broad portfolio of biological molecules that will enable it to activate endogenous NK and CD8+ T cells, and develop a T cell memory cancer vaccine to combat multiple tumor types without the use of high-dose chemotherapy.
In the field of infectious disease, NantCell’s goal is to develop vaccine therapy to treat and prevent diseases stemming from HIV, Influenza, Zika, and Ebola infection.
For more information please visit www.nantcell.com
Forward-Looking Statements
This press release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995.
Forward-looking statements include statements concerning or implying
that NantCell will be successful in improving the treatment of cancer.Risks and uncertainties related to this endeavor include, but are not
limited to, obtaining
Forward-looking statements are based on management's current expectations and are subject to various risks and uncertainties that could cause actual results to differ materially and adversely from those expressed or implied by such forward-looking statements. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements.
About NantOmics
NantOmics, a member of the
NantOmics has a highly scalable cloud-based infrastructure capable of storing and processing thousands of genomes a day, computing genomic variances in near real-time and correlating proteomic pathway analysis with quantitative gene expression and pharmacogenomic signatures, which guides the use of immunotherapies, chemotherapies and targeted therapies. Clinical studies for neoepitope vaccines using NantOmics’ proprietary technologies and novel artificial intelligence platforms are currently underway. For more information please visit www.nantomics.com.
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Source:
Media Contact:
Jen Hodson,
562-397-3639
Jen@nant.com
Investor
Contact:
David Pyrce
951-551-0949
david.pyrce@nantkwest.com