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Endocyte Presents Data from its CAR T Platform at American Association for Cancer Research (AACR) Annual Meeting 2018

On April 16, 2018 Endocyte, Inc. (Nasdaq:ECYT), a biopharmaceutical company developing targeted therapeutics for personalized cancer treatment, reported in a late-breaking poster session the presentation of new research from Endocyte’s chimeric antigen receptor T-cell (CAR T) adaptor molecule (CAM) platform at the AACR (Free AACR Whitepaper) Annual Meeting 2018 in Chicago, IL (Press release, Endocyte, APR 16, 2018, View Source [SID1234525341]).

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"We are pleased to present data that support the utility of our unique CAR T platform, which potentially enables us to control cytokine release syndrome (CRS), manage T-cell exhaustion and address heterogeneity in both solid and liquid tumors through the administration of multiple CAMs," said Chris Leamon, vice president, research and development of Endocyte. "These findings are critical towards identifying the dosing regimen and confirming the anti-tumor activity of EC17/CAR T, our folate-targeted CAM-based therapy, as we look to initiate a phase 1 trial in osteosarcoma later this year."

Endocyte’s CAM-based therapies consist of a single universal autologous CAR T-cell, designed to bind with high affinity to FITC. This universal CAR T-cell can be specifically directed to cancer cells through the administration of a bi-specific adaptor molecule targeted to both FITC and a tumor target, which acts to bridge the universal CAR T-cell with the cancer cells. This allows for control of the antigen target through the administration of the CAM, in contrast to current CAR T-cell therapies, in which the antigen targets are not controlled.

The data presented at AACR (Free AACR Whitepaper) show that EC17 penetrates solid tumors within minutes and is retained due to high affinity for the folate receptor (FR), while unbound EC17 rapidly clears from the blood and receptor-negative tissues. When tested against human xenografts, EC17/CAR T-cell therapy has shown consistent antitumor activity with low or no adverse reactions. For translation into first-in-human testing, clinically relevant dosing regimens were evaluated using tumor-free and tumor-bearing mice to study CAR T-cell proliferation, cytokine production and the onset/mitigation of CRS. Preclinically, EC17/CAR T-cell therapy has demonstrated meaningful efficacy against some of the more aggressive and chemo-resistant FR+ tumors of various histology.

Although CRS could be triggered in this study, it could also be mitigated, or even prevented, using intermittent dosing and/or dose titration of the EC17 CAM. Under extreme conditions where dose cessation failed, intravenous sodium fluorescein (NaFl) could be used as a fast-acting rescue agent to temporarily displace CAR T-cells from their targets and reverse the CRS.

Website Information
Endocyte routinely posts important information for investors on its website, www.endocyte.com, in the "Investors & News" section. Endocyte uses this website as a means of disclosing material information in compliance with its disclosure obligations under Regulation FD. Accordingly, investors should monitor the "Investors & News" section of Endocyte’s website, in addition to following its press releases, SEC filings, public conference calls, presentations and webcasts. The information contained on, or that may be accessed through, Endocyte’s website is not incorporated by reference into, and is not a part of, this document.

Deciphera Pharmaceuticals, Inc. Reports Updated Data from Ongoing Phase 1 Clinical Trial of DCC-2618 at 2018 American Association for Cancer Research (AACR) Annual Meeting

On April 16, 2018 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, reported the presentation of updated data from its ongoing Phase 1 clinical trial of DCC-2618, the Company’s broad spectrum KIT and PDGFRα inhibitor, in patients with gastrointestinal stromal tumors (GIST) (Press release, Deciphera Pharmaceuticals, APR 16, 2018, View Source [SID1234525340]). Filip Janku, M.D., Ph.D., Assistant Professor, The University of Texas MD Anderson Cancer Center presented the poster titled "Pharmacokinetic (PK), safety, and tolerability profile of DCC-2618 in a phase 1 trial supports 150 mg QD (once daily) selected for a pivotal phase 3 trial in gastrointestinal stromal tumors (GIST)" at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, IL. The poster includes an assessment of the safety and tolerability profile of DCC-2618 in 100 GIST patients treated at the recommended Phase 2 dose (RP2D) of 150 mg QD, which supports the selection of this dose for the ongoing pivotal, randomized Phase 3 INVICTUS study (NCT03353753).

"The data presented at AACR (Free AACR Whitepaper) provides a robust assessment of the safety and tolerability profile of DCC-2618 in GIST patients at the 150 mg QD dose selected for the INVICTUS pivotal Phase 3 study in fourth-line and fourth line plus GIST, which we initiated in January 2018," said Michael D. Taylor, Ph.D., President and Chief Executive Officer of Deciphera. "If successful, the INVICTUS study could serve as the basis for a New Drug Application (NDA), providing a much-needed therapeutic option for these patients for whom there are no approved treatment options. We also plan to initiate a second Phase 3 registration study later this year, evaluating DCC-2618 in second-line GIST patients who have progressed, or are intolerant to front-line therapy with imatinib."

The poster presentation includes the following highlights:
Safety and tolerability of DCC-2618 on 100 GIST patients treated at the 150 mg QD dose out of the total of 169 patients treated with DCC-2618, as of the cut-off date of January 18, 2018.
As of March 19, 2018, 81 of 137 GIST patients enrolled at the cut-off date and treated at 100 mg or more per day, remained on study treatment. In addition, 46 patients were treated for more than 6 months, including 10 patients who were treated for more than 12 months.
Employing a population pharmacokinetic (PK) model based on steady state exposure to DCC-2618 and the active metabolite, DP-5439, increasing doses of DCC-2618 resulted in dose proportional increases in the combined exposure.

Preliminary data from the 12 GIST patients dose escalated from 150 mg QD to 150 mg BID following progression by RECIST (Response Evaluation Criteria in Solid Tumors) are immature and do not currently support a conclusion regarding a benefit from intra-patient dose escalation.
Based on the 100 GIST patients treated at the RP2D dose of 150 mg QD, DCC-2618 was well-tolerated, supporting the use of this dose in the pivotal, randomized Phase 3 trial, INVICTUS (NCT03353753).

About DCC-2618
DCC-2618 is a KIT and PDGFRα kinase switch control inhibitor in clinical development for the treatment of KIT and/or PDGFRα-driven cancers, including gastrointestinal stromal tumors, systemic mastocytosis and glioblastoma multiforme. DCC-2618 was specifically designed to improve the treatment of GIST patients by inhibiting a broad spectrum of mutations in KIT and PDGFRα. DCC-2618 is a KIT and PDGFRα inhibitor that blocks initiating KIT mutations in exons 9, 11, 13, 14, 17, and 18, involved in GIST as well as the primary D816V exon 17 mutation involved in SM. DCC-2618 also inhibits primary PDGFRα mutations in exons 12, 14, and 18, including the exon 18 D842V mutation, involved in a subset of GIST.

Cellectar Presents Preclinical Data at AACR Annual Meeting Demonstrating the Ability of its PDCs to Selectively Target a Broad Range of Tumor Cells

On April 16, 2018 Cellectar Biosciences (Nasdaq: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported the presentation of a late breaker poster entitled "Phospholipid drug conjugates (PDC) show specificity for a broad range of tumor cells and provides a novel approach for targeted or precision therapy" at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting underway in Chicago (Press release, Cellectar Biosciences, APR 16, 2018, View Source [SID1234525339]). Jarrod Longcor, chief business officer at Cellectar Biosciences will present this poster today, from 8:00 am – 12:00 pm (CT), poster section 43.

The poster articulates how phospholipid ether platform provides tumor targeting for PDC molecules, irrespective of payload/warhead and their behavior once inside cells. These data provide valuable insight for the successful design of molecules for targeted delivery of cytotoxic payloads. In one of the studies presented, the result shows that Cellectar’s PDCs can effectively deliver cytotoxic payloads to the tumor cells without killing normal cells and that there is a 20-fold difference in the delivery of PDCs to the tumor versus normal cells.

"Many cancer treatments have clinical limitations that could be improved by the targeting our novel phospholipid ether technology and PDCs provide. Our research continues to suggest that our PDCs may offer an attractive method of targeting therapeutics to tumors. Our platform may provide distinct advantages over other technologies, not least of which is the diversity of payloads and linkers we can utilize," said James Caruso, chief executive officer of Cellectar Biosciences. "It is our goal to demonstrate that this level of diversity and specificity can translate into outcomes that will benefit cancer patients."

About Phospholipid Drug Conjugates
Cellectar’s product candidates are built upon a patented delivery and retention platform that utilizes optimized PDCs to target cancer cells. The PDC platform selectively delivers diverse oncologic payloads to cancerous cells and cancer stem cells, including hematologic cancers and solid tumors. This selective delivery allows the payloads’ therapeutic window to be modified, which may maintain or enhance drug potency while reducing the number and severity of adverse events. This platform takes advantage of a metabolic pathway utilized by all tumor cell types in all cell cycle stages. Compared with other targeted delivery platforms, the PDC platform’s mechanism of entry does not rely upon specific cell surface epitopes or antigens. In addition, PDCs can be conjugated to molecules in numerous ways, thereby increasing the types of molecules selectively delivered. Cellectar believes the PDC platform holds potential for the discovery and development of the next generation of cancer-targeting agents.

Preclinical Data Highlighting Uptake and Enhanced
Anti-Tumor Effects of Cellectar’s CLR 131 in Head and Neck
Cancer Presented at AACR Annual Meeting

On April 16, 2018 Cellectar Biosciences (Nasdaq: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported the presentation of CLR 131 preclinical data in a poster discussion entitled "Therapeutic Combination of Radiolabeled CLR1404 with External Beam Radiation in Head and Neck Cancer Murine Xenograft Models" at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting underway in Chicago (Press release, Cellectar Biosciences, APR 16, 2018, View Source [SID1234525338]). The discussion, hosted on Sunday, April 15, 2018 was led by Chunrong Li, assistant scientist, Department of Human Oncology, University of Wisconsin School of Medicine and Public Health.

The purpose of the study was to evaluate the anti-tumor effect of CLR 131 in combination with external beam radiation (XRT). The results demonstrated uptake of CLR 131 across multiple head and neck cancer (HNC) cell lines and xenograft models, and synergistic anti-tumor effects when CLR 131 was combined with XRT. The combination of CLR 131 and fractionated XRT showed enhanced tumor growth inhibition compared with single modality treatment in the 6 HNC xenograft models. Importantly, the findings suggest potential efficacy using CLR 131 combined with reduced-dose XRT in HNC patients. High-dose XRT while effective for localized disease, produces significant co-morbidities for patients, especially those suffering from diffuse disease. The potential to reduce the XRT dose may also result in decreased toxicity to normal tissue, a common side effect of high-dose XRT.

As a key milestone of their Head and Neck SPORE Grant (NIH P50 DE026787), the University of Wisconsin-Madison is initiating the first human clinical trial combining CLR 131 and external beam radiation in patients with recurrent HNC in the second half of 2018. The costs associated with the Phase 1 study will be covered in their entirety through the grant and the study represents a fourth clinical trial using the company’s lead PDC, CLR 131.

"As we continue both preclinical and clinical evaluation of our lead cancer targeting compound CLR 131, our potential to meaningfully impact a broad range of cancers continues to grow," said James Caruso, chief executive officer of Cellectar Biosciences. "We are encouraged by the data highlighted at AACR (Free AACR Whitepaper) showing enhanced receptivity to treatment and inhibition of tumor growth, while potentially reducing toxicities associated with current standard of care treatment."

About CLR 131
CLR 131 is Cellectar’s investigational radioiodinated PDC therapy that exploits the tumor-targeting properties of the company’s proprietary phospholipid ether (PLE) and PLE analogs to selectively deliver radiation to malignant tumor cells, thus minimizing radiation exposure to normal tissues. CLR 131, is in a Phase 2 clinical study in relapsed or refractory (R/R) MM and a range of B-cell malignancies and a Phase 1 clinical study in patients with (R/R) MM exploring fractionated dosing . In 2018 the company plans to initiate a Phase 1 study with CLR 131 in pediatric solid tumors and lymphoma, and a second Phase 1 study in combination with external beam radiation for head and neck cancer.

Cancer Genetics’ Unique Tissue of Origin Test (TOO®) Receives Special FDA 510(k) Clearance

On April 16, 2018 Cancer Genetics, Inc. (Nasdaq:CGIX), a leader in enabling precision medicine for oncology through molecular markers and diagnostics, reported that it has received special 510(k) clearance from the U. S. Food and Drug Administration (FDA) for its Tissue of Origin test (TOO) following modifications made to test reagents and software (Press release, Cancer Genetics, APR 16, 2018, View Source [SID1234525337]).

TOO is a microarray-based gene expression test that analyzes a tumor’s genomic information to help identify its origin, which is valuable in classifying metastatic, poorly differentiated, or undifferentiated cancers. TOO assesses 2,000 individual genes, covering 15 of the most common tumor types (representing 58 morphologies) and 90% of all solid tumors [1]. These tumors include thyroid, breast, non-small cell lung, pancreas, gastric, colorectal, liver, bladder, kidney, non-Hodgkin’s lymphoma, melanoma, ovarian, sarcoma, testicular germ cell, and prostate.
TOO is the only FDA-cleared test of its type and is Medicare-reimbursed. It is also the only test that provides a pathologist’s review and interpretation of a patient’s test results and diagnosis. TOO provides extensive analytical and clinical validation for statistically significant improvement in accuracy over other methods, including IHC [2]. TOO results lead to a change in patient treatment 65% of the time. In challenging cancers that require a second round of IHC, TOO increases diagnostic accuracy and confidence in site-specific treatment decisions [1].
"Our TOO Test represents a unique offering with the ability to add significant value to the continuum of care for cancer patients and greatly enhance our biopharma partners’ development efforts. This 510(k) clearance represents an important milestone toward our goal of gaining broad adoption of the test," said John A. (Jay) Roberts, Interim Chief Executive Officer and COO of Cancer Genetics. "An important element of our recently implemented transformation strategy is the identification of new methods through which to monetize our world-class test portfolio. We are currently evaluating several partnering opportunities that would expand the reach of the TOO Test and have the potential to generate high-margin revenue streams. We look forward to continuing this process as we leverage the capabilities of TOO to drive future growth."

Compared to the early version, the current TOO assay uses new labeling reagents and has a higher accuracy rate and a shorter workflow with similar precision and reproducibility. The low RNA input requirement of the early version is maintained. The combined result of these new features offers a further optimized clinical assay to help clinicians make diagnostic decisions and subsequent treatment selections.

Rita Shaknovich, Chief Medical Officer of CGI added, "Despite increasing excellence in the diagnostic workup for malignancies, there are approximately 150,000 newly diagnosed cases of metastatic cancer with unclear diagnosis in the U.S. and Europe each year [3]. This includes the subset of patients with cancers of unknown primary (CUP) and of uncertain origin. Increasingly complex algorithms and testing associated with a diagnostic workup also means that many challenging cases have insufficient amount of sample material for analysis. CGI’s TOO aids in identifying the source of such challenging tumors while using less material, and could be used as a diagnostic or confirmatory tool both for routine clinical testing and for clinical trial enrollment of patients with such tumors, enabling them to be considered for novel drug therapies."
The Company announced on April 2, 2018 that it has engaged Raymond James & Associates, Inc. as a financial advisor to assist with evaluating options for the Company’s strategic direction. These options may include raising additional capital, the acquisition of another company and / or complementary assets, the sale of the Company, or another type of strategic partnership. The Company’s Board of Directors is committed to evaluating all potential strategic opportunities and to pursuing the path most likely to create both near- and longer-term value for Cancer Genetics’ shareholders.
1. R Pillai, et al. Validation and Reproducibility of a Microarray-based Gene Expression Test for Identifying the Primary Site of Tumors in Formalin-Fixed Paraffin-Embedded Specimens. J Molec Diag 13 2011;13:48-56.
2. JP Grenert, et al. Gene Expression Profiling from Formalin-Fixed, Paraffin-Embedded Tissue for Tumor Diagnosis. Clin Chim Acta. 2011 Jul 15;412(15-16):1462-4.
3. Tomuleasa, Ciprian, et al. How to Diagnose and Treat a Cancer of Unknown Primary Site. Journal of Gastrointestinal & Liver Diseases 26.1 (2017).