1stOncology™: Cancer Intelligence Service – Page 15977 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

10-Q – Quarterly report [Sections 13 or 15(d)]

Sorrento Therapeutics has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, Sorrento Therapeutics, 2017, NOV 9, 2017, View Source [SID1234521834]).

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!

10-Q – Quarterly report [Sections 13 or 15(d)]

Onconova has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, Onconova, 2017, NOV 9, 2017, View Source [SID1234521831]).

10-Q – Quarterly report [Sections 13 or 15(d)]

Lixte Biotechnology has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, Lixte Biotechnology, 2017, NOV 9, 2017, View Source [SID1234521830]).

Seattle Genetics Announces FDA Approval of ADCETRIS® (Brentuximab Vedotin) for Primary Cutaneous Anaplastic Large Cell Lymphoma (pcALCL) and CD30-Expressing Mycosis Fungoides (MF)

On November 9, 2017 Seattle Genetics, Inc. (Nasdaq: SGEN) reported that the U.S. Food and Drug Administration (FDA) has approved ADCETRIS (brentuximab vedotin) for the treatment of adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) and CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy (Press release, Seattle Genetics, NOV 9, 2017, View Source;p=RssLanding&cat=news&id=2315957 [SID1234521902]). Primary cutaneous ALCL and MF are the most common subtypes of cutaneous T-cell lymphoma (CTCL). The approval is based on data from the phase 3 ALCANZA trial and two phase 2 investigator-sponsored trials. The phase 3 ALCANZA study was designed to compare ADCETRIS monotherapy administered every three weeks versus physician’s choice of representative standard of care options, methotrexate or bexarotene. The trial met its primary endpoint with the ADCETRIS treatment arm demonstrating a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4) versus the control arm as assessed by an independent review facility. ORR4 was 56.3 percent (95% CI: 44.1, 68.4) in the ADCETRIS arm compared to 12.5 percent (95% CI: 4.4, 20.6) in the control arm (p-value <0.001). The most common adverse reactions (≥ 20 percent) were: anemia, peripheral sensory neuropathy, nausea, diarrhea, fatigue and neutropenia.

This is the fourth FDA-approved indication for ADCETRIS, which also has: (1) regular approval for treatment of classical Hodgkin lymphoma (cHL) patients who fail autologous hematopoietic stem cell transplantation (auto-HSCT) or who fail at least two prior multi-agent chemotherapy regimens and are not auto-HSCT candidates, (2) regular approval for the treatment of patients with cHL at high risk of relapse or progression as post-auto-HSCT consolidation, and (3) accelerated approval for treatment of systemic anaplastic large cell lymphoma (sALCL) patients who fail at least one prior multi-agent chemotherapy regimen. Accelerated approval in the sALCL indication is based on overall response rate, and continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

In November 2016, the FDA granted ADCETRIS Breakthrough Therapy Designation (BTD) for the treatment of patients with pcALCL and CD30-expressing MF who require systemic therapy and have received one prior systemic therapy. The FDA also granted Priority Review for the supplemental Biologics License Application (BLA), and the Prescription Drug User Fee Act (PDUFA) target action date was December 16, 2017.

"Cutaneous T-cell lymphoma is a blood cancer of the skin with no known cure and few new treatment options. It is a disfiguring disease in dire need of more effective and durable treatment options to help keep this debilitating and painful disease at bay," said Susan Thornton, cutaneous lymphoma patient and chief executive officer of the Cutaneous Lymphoma Foundation (CLF). "As both a patient and representative of the cutaneous lymphoma community, we welcome the FDA approval of ADCETRIS as a new treatment option for the most common subtypes of cutaneous T-cell lymphoma in patients who require systemic therapy and we look forward to sharing this important milestone with patients and physicians."

"Our phase 3 ALCANZA clinical trial evaluating ADCETRIS in patients with primary cutaneous anaplastic large cell lymphoma and mycosis fungoides, which are the most common types of cutaneous T-cell lymphoma, demonstrated superior efficacy with durable responses for long-term disease management when compared to standard of care treatment options methotrexate and bexarotene," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "These data, along with data from investigator-sponsored clinical trials, led to the FDA approval of ADCETRIS as a treatment for patients with pcALCL or CD30-expressing MF, which represent the most common subtypes of CTCL. This FDA approval, which was granted more than a month in advance of the PDUFA date, represents a significant milestone for the lymphoma community. Our goal is to establish ADCETRIS as the foundation of care in CD30-expressing lymphomas and this approval represents our fourth FDA-approved indication."

The FDA approval is based primarily on positive results from a phase 3 trial called ALCANZA that were presented at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December 2016 and published online in the Lancet in June 2017. Results from the ALCANZA trial in 128 pcALCL and CD30-expressing MF patients requiring systemic therapy included:

The trial achieved its primary endpoint with the ADCETRIS treatment arm demonstrating a highly statistically significant improvement in the rate of ORR4 versus the control arm as assessed by an independent review facility. ORR4, as assessed by Global Response Score, was 56.3 percent in the ADCETRIS arm compared to 12.5 percent in the control arm (p-value <0.001).
Key secondary endpoints specified in the protocol, including objective response rate, complete response rate and progression-free survival, were all highly statistically significant in favor of the ADCETRIS arm.
The objective response rate in the ADCETRIS arm was 67.2 percent (95% CI: 55.7, 78.7) compared to 20.3 percent (95% CI: 10.5, 30.2) in the control arm.
The CR rate in the ADCETRIS arm was 15.6 percent (95% CI: 7.8, 26.9) compared to 1.6 percent (95% CI: 0, 8.4) in the control arm (p-value = 0.0066).
The median PFS in the ADCETRIS arm was 16.7 months (95% CI: 14.9, 22.8) compared to 3.5 months (95% CI: 2.4, 4.6) in the control arm (HR 0.270; 95% CI, 0.169, 0.430; p-value <0.001).
The safety profile associated with ADCETRIS from the ALCANZA trial was generally consistent with the existing prescribing information. The most common adverse events occurring in 20 percent or more of patients of any grade include: anemia, peripheral sensory neuropathy, nausea, diarrhea, fatigue and neutropenia.
Additional data from two investigator-sponsored phase 2 trials evaluating ADCETRIS in 73 MF patients were also incorporated into the supplemental BLA representing a broader spectrum of CD30-expression levels than that of the ALCANZA trial.

About CTCL

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Cutaneous lymphomas are a category of non-Hodgkin lymphoma that primarily involve the skin. According to the Cutaneous Lymphoma Foundation, CTCL is the most common type of cutaneous lymphoma and typically presents with red, scaly patches or thickened plaques of skin that often mimic eczema or chronic dermatitis. The most common subtypes of CTCL include mycosis fungoides and primary cutaneous anaplastic large cell lymphoma. Progression from limited skin involvement may be accompanied by skin tumor formation, ulceration and exfoliation, complicated by itching and infections. Advanced stages are defined by involvement of lymph nodes, peripheral blood and internal organs.

According to the American Cancer Society and the Leukemia and Lymphoma Society, CTCL represents approximately four percent of non-Hodgkin lymphoma, which is about 2,800 patients. Not all newly diagnosed patients require systemic therapy. The standard treatment for systemically pretreated CTCL includes skin-directed therapies, radiation and systemic therapies. The systemic therapies currently approved for treatment have demonstrated 30 to 45 percent objective response rates, with low complete response rates.

NanoString Highlights Record Number of nCounter-Based Research Abstracts at the 2017 Annual Meeting of the Society of Immunotherapy of Cancer (SITC)

On November 9, 2017 NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, reported the highlights of numerous advances in understanding immune response and cancer immunotherapy using the nCounter platform that will be presented at the 32nd Annual Meeting of the Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, Ligand, NOV 9, 2017, View Source [SID1234521879]).

"The scope of nCounter-based research being presented at this year’s SITC (Free SITC Whitepaper) conference demonstrates our scientific and commercial momentum in immuno-oncology," said Alessandra Cesano, chief medical officer of NanoString. "In addition, several abstracts outline the unique capabilities of our Digital Spatial Profiling technology to characterize the tumor and its microenvironment to inform cancer research and drug development."

At least 45 abstracts using NanoString’s nCounter platform will be presented at the SITC (Free SITC Whitepaper) Annual Meeting, being held in National Harbor, Maryland, Nov. 8-12, 2017. The research being presented spans a wide breadth of applications including biomarker development, assessing the biology of immune responsiveness and resistance, and digital pathology. They include biomarker studies covering 21therapeutic agents, as single agents or in combination.

Nineteen studies used NanoString’s PanCancer Series of panels to explore biomarkers associated with response to immunotherapy. Fourteen of these studies incorporate NanoString’s best-selling PanCancer Immune Profiling Panel. An additional five studies incorporating both early access and commercial versions of NanoString’s new PanCancer IO 360 Panel. The PanCancer IO 360 Panel assays key pathways from the tumor, the microenvironment and the immune system and includes more than 20 signatures that are potentially associated with therapeutic response to novel therapeutic agents with "matched" mechanisms of action. Three additional studies incorporate the nCounter Hallmarks of Cancer suite of gene expression panels, which includes three panels covering Cancer Immune Profiling, Cancer Pathways, and Cancer Progression.

The PanCancer IO 360 Panel studies provide initial evidence of positive association between the Tumor Inflammation Signature scores and clinical response to different immuno-oncology agents including nivolumab, ipilimumab, pembrolizumab and entinostat. NanoString’s Tumor Inflammation Signature (TIS) was recently described by Ayers, et al. (View Source) and is included in the PanCancer IO360 panel. The Tumor Inflammation Signature measures the presence or absence of a peripherally suppressed adaptive immune response within the tumor.

Five studies cover the use of NanoString’s Digital Spatial Profiling (DSP) platform in immuno-oncology research. DSP allows for digital quantification of protein from discrete regions of FFPE tissue in an automated and multiplex format. DSP will become widely available with the launch of a new instrument planned for late 2018, and in the meantime is available under a Technology Access Program.

Two studies cover the use of 3D Biology panels and demonstrate the utility of the nCounter platform. NanoString’s 3-D Flow technology provides detailed molecular profiles of T cell populations, and enables unique, simultaneous analysis of high-plex protein and RNA data. 3D Biology and 3D Flow approaches can be used to characterize baseline immunological state and response to stimulation, which may be useful for profiling mechanisms of action or therapeutic response.

At the 2017 SITC (Free SITC Whitepaper) Annual Meeting, NanoString will showcase its nCounter platform, IO360 Data Analysis, Digital Spatial Profiling and 3D Biology capabilities at booth #605.

NanoString will host a Digital Spatial Profiling Educational Session on Nov. 11, 2017, 12:45 – 1:45 p.m.

Below is a summary of abstracts co-authored by NanoString employees:

Abstract # Title Hyperlink
05 A dendritic cell targeting NY-ESO-1 vaccine significantly augments early and durable immune responses in melanoma patients pretreated with human Flt-3 Ligand View Source

019 ENCORE-601: Phase 1b/2 study of entinostat (ENT) in combination with pembrolizumab (PEMBRO) in patients with non-small cell lung cancer (NSCLC) View Source

P40 Deep proteomic and transcriptomic analysis of sorted T cells with a simple, integrated workflow View Source

P43 Assessment of Pharmacodynamic Effects of Immuno-Oncology Agents in Cynomolgus Monkeys using High-Content Gene Expression Profiling View Source

P64 Analytical Validation of Digital Spatial Profiling – a novel approach for multiplexed characterization of protein distribution and abundance in FFPE tissue sections View Source

P65 Spatially-resolved, multiplexed digital characterization of protein abundance in FFPE tissue sections: application in preclinical mouse models View Source

P66 Digital spatial profiling platform allows both spatially-resolved, multiplexed measurement of solid tumor and immune-associated protein distribution and abundance using a single FFPE tissue section View Source

P72 Analysis of biomarkers from a cohort of advanced melanoma patients previously exposed to immune checkpoint inhibition treated with entinostat (ENT) and pembrolizumab (PEMBRO).

View Source
P73 First-in-human neoadjuvant study of the immunogenomic impact of the oral IDO inhibitor epacadostat (INCB024360) on the tumor microenvironment of advanced ovarian cancer View Source

P98 Immunological profiling of baseline and resected biopsies from locally/regionally advanced/recurrent melanoma treated with neoadjuvant combination ipilimumab (3mg/kg or 10mg/kg) and high dose IFN-α2B View Source

P99 Biomarker analysis from the OpACIN trial (Neo-/adjuvant ipilimumab + nivolumab (IPI+NIVO) in palpable stage 3 melanoma) View Source

P100 Pretreatment gene expression correlation with clinical response to pembrolizumab or nivolumab in metastatic melanoma View Source

P383 Molecular and immune characterization of melanoma metastases with heterogeneous PTEN expression View Source

P485 Use of the NanoString Gene Expression Profiling Platform to Capture the Immunological Status of the Leukemia Microenvironment View Source

P512 Deep immunoprofiling of rare T-cell populations from clinical samples View Source

P524 Clinical and biomarker analyses of a phase II study of intratumoral tavokinogene telseplasmid (pIL-12) plus pembrolizumab in stage III/IV melanoma patients predicted to not respond to anti-PD-1 View Source