On June 4, 2018 Castle Biosciences, Inc., the skin cancer diagnostics company providing molecular diagnostics to improve cancer treatment decisions, reported the presentation of data highlighting the accuracy and performance of the DecisionDx-Melanoma gene expression profile (GEP) test at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held in Chicago, IL from June 1-5 (Press release, Castle Biosciences, JUN 4, 2018, View Source [SID1234527135]).

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The study titled, "Performance of a 31-gene expression profile melanoma test in clinically relevant clinicopathologic subgroups" (Abstract #9583), will be presented as a poster at the meeting. Results from the 690-patient study show that the DecisionDx-Melanoma test improved clinical risk prediction independent of traditional factors and consistent with findings from previous retrospective and prospective studies.

Key Study Findings:

Results from this multicenter study in 690 patients confirm that the DecisionDx-Melanoma test is an independent predictor of risk for recurrence, metastasis and melanoma-specific death, including clinically relevant subgroups.
The subgroup of American Joint Committee on Cancer (AJCC) Stage I-IIA patients who had a Class 2B result (highest risk) had significantly worse recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and melanoma-specific survival (MSS) rates compared to patients with a Class 1A result (lowest risk), important considerations that could impact surveillance and follow-up decisions.
For Stage IIIA patients, the DecisionDx-Melanoma test identified groups of patients with significantly different outcomes, which is increasingly important to inform decisions on adjuvant therapy and surveillance plans.
"Results from this multicenter study demonstrate that the GEP test can complement traditional AJCC staging factors by providing independent information that improves risk prediction for patients with melanoma," commented Brian Gastman, M.D., Cleveland Clinic Lerner Research Institute, Cleveland, Ohio. "With new options for patients increasing at a rapid pace, many clinical decisions are being made based on extrapolating data from different studies. Having additional, objective information is important to help patients and their treating physicians make definitive decisions, especially when there isn’t a clearly defined management plan."

Study Details:

Data from three previous DecisionDx-Melanoma validation studies were combined to enable analysis of clinically relevant subgroups. In this cumulative population of 690 Stage I-III patients, median age was 59 years, median time of follow-up was 6.5 years and median Breslow thickness was 1.3 mm. Seventy percent of patients had Stage I or II melanoma. The DecisionDx-Melanoma test was performed to determine molecular class for each patient, with a Class 1A result indicating the lowest 5-year risk of metastasis and a Class 2B result indicating the highest risk. Study endpoints included RFS (time to regional or distant metastatic event), DMFS (time to any metastatic event beyond the regional nodal basis) and MSS (time from diagnosis to death from melanoma).

Results confirm the prognostic accuracy of the DecisionDx-Melanoma test showing a significant difference among 5-year RFS rates for all groups. Patients with a Class 1A (lowest risk) result had an average RFS of 90% compared to 37% for Class 2B (highest risk) patients (p<0.0001). DMFS 5-year rates were 94% for Class 1A and 50% for Class 2B (p<0.0001). MSS 5-year rates were 99% for Class 1A and 75% for Class 2B (p<0.0001).

Based on Cox multivariate analysis in the Stage I-IIA subgroup, DecisionDx-Melanoma test class was found to be the only significant predictor of all three endpoints (RFS, DMFS and MSS; p<0.05 for all).

Additional Castle Biosciences Data at ASCO (Free ASCO Whitepaper) 2018

Preliminary data from the cutaneous squamous cell carcinoma (cSCC) development program will also be presented as a poster at the ASCO (Free ASCO Whitepaper) 2018 meeting (Abstract #9577). The study reports that preliminary gene expression based predictive models may offer important information about patient risk that builds on current staging methods. Results support the feasibility of the program to develop a clinically valuable test to predict which cSCC patients are at higher risk for local recurrence or regional/distant metastasis.

Additionally, an abstract highlighting the use of the DecisionDx-Melanoma test to identify a population of melanoma patients to assess risk of sentinel lymph node biopsy positivity (Abstract #e21611) will be included in the online ASCO (Free ASCO Whitepaper) 2018 proceedings.

About DecisionDx-Melanoma

The DecisionDx-Melanoma test uses tumor biology to predict individual risk of melanoma recurrence and sentinel lymph node positivity independent of traditional factors. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in three multi-center studies that have included 690 patients and have demonstrated consistent results. Performance has also been confirmed in four prospective studies including 702 patients. The consistent high performance and accuracy demonstrated in these studies, which combined have included over 1,300 patients, provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. Prediction of the likelihood of sentinel lymph node positivity has also been validated in two prospective multicenter studies that included over 1,400 patients. Clinical impact has been demonstrated in multi-center and single-center studies showing that test results impact clinical management decisions for one of every two patients tested. More information about the test and disease can be found at www.SkinMelanoma.com.

On June 4, 2018 Pfizer Inc. (NYSE:PFE) reported overall survival (OS) data from the ARCHER 1050 trial evaluating dacomitinib as a first-line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR-activating mutations compared to gefitinib (Press release, Pfizer, JUN 4, 2018, View Source [SID1234527151]). The trial showed a median OS of 34.1 months for patients receiving dacomitinib (95% CI: 29.5, 37.7), representing a more than seven-month improvement compared to 26.8 months with gefitinib (95% CI: 23.7, 32.1). The OS data from ARCHER 1050 were presented today as an oral presentation [Abstract #9004] at the 54th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago and have been published simultaneously in the Journal of Clinical Oncology.

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"Overall survival is an important measure to assess efficacy of investigational compounds. These data presented today are particularly significant as dacomitinib is the first EGFR tyrosine kinase inhibitor in a Phase 3 head-to-head study comparing two tyrosine kinase inhibitors to show an improvement in overall survival," said Professor Tony Mok, Chair of Department of Clinical Oncology, The Chinese University of Hong Kong. "I look forward to having dacomitinib as a potential first-line treatment option for non-small cell lung cancer patients with EGFR-activating mutations."

Overall survival was a secondary endpoint of ARCHER 1050, a randomized, open label Phase 3 study comparing the efficacy and safety of dacomitinib to gefitinib for the first-line treatment of locally advanced or metastatic NSCLC in subjects with EGFR-activating mutations. At the OS data cutoff, median OS was 34.1 months with dacomitinib (95% CI: 29.5, 37.7) compared to 26.8 months with gefitinib (95% CI: 23.7, 32.1). Patients receiving dacomitinib had a 56.2 percent survival rate at 30 months compared with 46.3 percent for patients who received gefitinib. Subgroup analyses were consistent with the primary OS analysis across most baseline characteristics, including patients with common sub-mutations exon 19 and 21.

The adverse events (AEs) observed with dacomitinib in the study were consistent with findings from previous dacomitinib trials. The most common AEs were diarrhea (87%), nail changes (62%), rash/dermatitis acneiform (49%) and mouth sores (44%). The most common Grade 3 AEs with dacomitinib were rash (14%) and diarrhea (8%). Grade 4 AEs occurred in two percent of dacomitinib-treated patients. There was one case of Grade 5 diarrhea and one case of Grade 5 liver disease. The discontinuation rate due to treatment-related AEs for dacomitinib was 10 percent compared to seven percent for gefitinib.

"What is most encouraging about these results is that patients with non-small cell lung cancer harboring EGFR-activating mutations who received dacomitinib achieved a median overall survival of nearly three years, a marked improvement compared to an established treatment in this setting," said Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global Product Development. "With today’s podium presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting and the U.S. Food and Drug Administration Priority Review granted earlier this year, we are encouraged by these data and committed to deliver this promising investigational medicine to patients as quickly as possible."

In April 2018, the U.S. Food and Drug Administration (FDA) granted priority review for dacomitinib for the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR-activating mutations. The FDA Prescription Drug User Fee Act (PDUFA) target action date is in September 2018. The European Medicines Agency also accepted the Marketing Authorization Application for dacomitinib for the same indication.

About Dacomitinib

Dacomitinib is an investigational, oral, once-daily, irreversible pan-human epidermal growth factor receptor tyrosine kinase inhibitor (TKI). It has not received regulatory approval in any country.

In 2012, Pfizer and SFJ Pharmaceuticals entered into a collaborative development agreement to conduct ARCHER 1050 across multiple sites.

About Non-Small Cell Lung Cancer

Lung cancer is the leading cause of cancer deaths worldwide.1 Non-small cell lung cancer (NSCLC) accounts for about 85 percent of lung cancer cases and remains difficult to treat, particularly in the metastatic setting.2 Biomarker therapies dramatically changed the care of patients with metastatic NSCLC. Approximately 75 percent of NSCLC patients are diagnosed late with metastatic or advanced disease where the five-year survival rate is only five percent.2,3,4

EGFR is a protein that helps cells grow and divide. When the EGFR protein is mutated it can cause cancer cells to form. EGFR mutations occur in 10 to 35 percent of NSCLC tumors globally, yet the disease is associated with low survival rates and disease progression remains a challenge.5,6

On June 4, 2018 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company") reported to confirm that it is involved in three poster presentations at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)‘s (ASCO) (Free ASCO Whitepaper) Annual Meeting, in Chicago, Illinois taking place from 1 – 5 June (Press release, Immutep, JUN 4, 2018, View Source [SID1234527167]). All three posters relate to Immutep’s lead product candidate eftilagimod alpha ("efti" or "IMP321").

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Two of the posters (TPS1050 and TPS1109), were presented on June 2, and focused on the Company’s Phase IIb AIPAC (Active Immunotherapy PAClitaxel) double blind placebo trial evaluating the efficacy of efti in patients with metastatic breast cancer.

The first poster discussed the results from the safety run-in phase of the AIPAC trial, which have been previously announced to the market. This poster was presented by Prof. Duhoux, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain. Specifically, it reiterated that the overall response rate ("ORR") in patients to the combination of paclitaxel and efti was 47%, and that the disease control rate ("DCR") was 87%. It also noted that two of the responses to the combination therapy occurred relatively late in the treatment (after ~6 months) and that the safety run-in phase reported a very encouraging safety profile.

The second poster, presented by Dr. Dirix of GZA Hospitals Sint-Augustinus, Antwerp, Belgium, outlined the ongoing AIPAC trial, its design and primary end points.

The third poster (TPS3129) outlines the clinical trial design of the ongoing INSIGHT clinical trial, an open-labeled Phase I study to evaluate the feasibility and safety of intra-tumoral, intra-peritoneal, and subcutaneous injections with efti for advanced stage solid tumors. This is an investigator sponsored trial by Immutep’s partner, IKF in Frankfurt, Germany, which will be presented by the investigator on June 5 in Chicago.

The ASCO (Free ASCO Whitepaper) posters regarding the Company’s AIPAC trial can be accessed via the Immutep website under the Presentations tab at:

View Source

About the AIPAC clinical trial

The ongoing AIPAC (Active Immunotherapy PAClitaxel) Phase IIb clinical trial is a European multi-centre study evaluating eftilagimod alpha ("efti" or "IMP321") in combination with paclitaxel in metastatic breast cancer (clinicaltrials.gov identifier NCT 02614833). To date, 33 out of a planned 34 clinical sites across Belgium, the Netherlands, Poland, Hungary, United Kingdom, France and Germany are now actively recruiting and treating patients. The AIPAC study is currently expected to be fully recruited with 226 patients by the end of calendar 2018, with first Progression Free Survival data expected in calendar 2019.

About the INSIGHT clinical trial

The on-going INSIGHT Phase I clinical trial is an investigator initiated, explorative, single centre, open-label, study evaluating the feasibility and safety of intra-tumoural, intra-peritoneal, and subcutaneous injections of efti for advanced stage solid tumour entities (clinicaltrials.gov identifier NCT03252938). The Lead Investigator of this clinical trial is Professor Doctor Salah-Eddin Al-Batran, the Medical Director of the IKF.

On June 4, 2018 Progenics Pharmaceuticals, Inc. (Nasdaq:PGNX), an oncology company developing innovative medicines and other products for targeting and treating cancer, reported updated overall survival data from the Company’s pivotal Phase 2 trial of its targeted, high-specific-activity radiotherapeutic candidate, AZEDRA (iobenguane I 131), in patients with malignant, recurrent, or unresectable pheochromocytoma and paraganglioma (pheo/para), which is the subject of an oral presentation at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois (Press release, Progenics Pharmaceuticals, JUN 4, 2018, View Source [SID1234527185]).

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"This pivotal study, the largest prospective clinical trial in pheochromocytoma and paraganglioma to date, has demonstrated multiple clinical benefits of AZEDRA treatment, which has translated into impressive overall survival data in this highly pre-treated and advanced patient population," said Dr. Daniel Pryma, Associate Professor of Radiology & Radiation Oncology and Chief, Division of Nuclear Medicine & Clinical Molecular Imaging at the Perelman School of Medicine at the University of Pennsylvania, the trial’s lead investigator. "The primary cause of death in pheo/para patients is tumor progression. In this study, 98% of patients who received two doses experienced stable disease or better as measured by Response Evaluation Criteria In Solid Tumors (RECIST). In addition, 30% of pheo/para patients die from complications due to catecholamine-associated hypertension, while patients treated with AZEDRA were able to achieve control of catecholamine-associated hypertension and a sustained reduction of antihypertensive medications. These benefits were correlated with a robust tumor biomarker response. With no approved therapies in the U.S. for pheo and para, AZEDRA has the potential to offer a meaningful treatment option for patients with these life-threatening tumors."

Dr. Pryma will review the data today in an oral presentation entitled, "AZEDRA (iobenguane I 131) in patients with malignant, recurrent and/or unresectable pheochromocytoma or paraganglioma (PPGL): Updated efficacy and safety results from a multi-center, open-label, pivotal phase 2 study."

The pivotal phase 2 open-label, multi-center trial was conducted under a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA). The trial met the primary endpoint evaluating the proportion of pheochromocytoma and paraganglioma patients who achieved a 50% or greater reduction of all antihypertensive medication for at least six months, and showed favorable results from a key secondary endpoint evaluating the proportion of patients with overall tumor response as measured by RECIST. 92.2% of patients treated with at least one therapeutic dose of AZEDRA achieved a confirmed partial response or stable disease by 12 months. AZEDRA was also shown to be safe and generally well tolerated.

Median overall survival time as of December 4, 2017 was 37 months from first AZEDRA therapeutic dosing in the overall study population, and 44 months among patients who received two therapeutic doses, compared to 18 months among patients who received only one therapeutic dose. The study data also suggest the potential for AZEDRA to extend survival in patients with liver or lung metastasis, which is generally considered in the literature to be less than 24 months. In this study, median survival time was similar in patients with lung or liver metastasis compared to those without (43 vs. 41 months). Long term follow-up continues.

"These data, which are the basis of our New Drug Application, show that AZEDRA has the potential to address the dual goals of therapy in pheo and para – to reduce the cardiovascular symptoms associated with the excess hormone production, and to produce favorable tumor responses," said Mark Baker, Chief Executive Officer of Progenics. "We are eagerly anticipating the FDA’s decision on AZEDRA, as we believe it has the potential to be a breakthrough treatment option for patients with these deadly, ultra-rare neuroendocrine cancers."

About AZEDRA

AZEDRA (iobenguane I 131) is a high-specific-activity radiotherapeutic product candidate in development as a treatment for malignant, recurrent, or unresectable pheochromocytoma and paraganglioma, which are rare neuroendocrine tumors of neural crest origin. AZEDRA is a substrate for norepinephrine reuptake transporter, which is highly expressed on the cell surface of neuroendocrine tumors. AZEDRA has been granted Orphan Drug designation, Fast Track status, and Breakthrough Therapy designation in the U.S. Under a SPA agreement with the FDA, a Phase 2 pivotal study has been completed in patients with malignant, recurrent, or unresectable pheochromocytoma and paraganglioma. The FDA granted Priority Review of Progenics’ New Drug Application and has set an action date of July 30, 2018 under the Prescription Drug User Fee Act. There are currently no FDA-approved therapies for the treatment of these ultra-rare diseases.

About Pheochromocytoma and Paraganglioma

Pheochromocytoma and paraganglioma are rare neuroendocrine tumors that arise from cells of the autonomic nervous system. Pheochromocytoma forms in the adrenal medulla, whereas paragangliomas form outside the adrenal gland. Standard treatment options for these tumors include surgery, palliative therapy and symptom management. Pheochromocytoma and paraganglioma tumors frequently secrete high levels of hormones that can lead to life-threatening hypertension, heart failure, and stroke in these patients. Malignant and recurrent pheochromocytoma and paraganglioma may result in unresectable disease with a poor prognosis, representing a significant management challenge with very limited treatment options and no approved anti-tumor therapies.

On June 4, 2018 Transgene (Paris:TNG), a biotech company that designs and develops virus-based immunotherapies against cancers and infectious diseases, and University of Leeds, reported that new clinical data1 obtained with Pexa-Vec further demonstrate anti-tumor activity after intravenous (i. v.) infusion (Press release, Transgene, JUN 4, 2018, View Source [SID1234621826]). These data were presented by Dr. Alan Anthoney (University of Leeds) in a poster presentation at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, June 4, in Chicago .

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These first clinical results confirm Pexa-Vec’s activation of anti-tumor immunity and targeted oncolytic activity. The key findings of the trial show:

selective expression and replication of Pexa-Vec in the tumor tissues;
induction of a robust anti-tumor immune response:
with the stimulation of an adaptive response (T cells) targeted to tumor specific antigens,
the activation of innate immune response (NK cells), and
an elevation of cytokines associated with immune stimulation;
one partial and one complete necrosis of tumors among the patients with colorectal cancer and liver metastases (pathological responses);
upregulation of PD-L1 and PD-1 signaling molecules, a finding that strongly supports the rationale for combining Pexa-Vec with anti-PD-1 inhibitors.
Dr Alan Anthoney, Consultant in Medical Oncology at Leeds Teaching Hospitals, Senior Lecturer in the Institute of Cancer & Pathology at the University of Leeds and principal investigator of the trial, said: "We are very encouraged to report that a single IV administration of Pexa-Vec displayed cytolytic activity at tumor sites, where it elicited a robust activation of tumor-antigen specific immune cells. In one patient with colorectal cancer liver metastasis a complete pathological response has been observed. These data clearly support the anti-tumor activity of Pexa-Vec. The final data from this trial will be published in an upcoming paper. Our decision to lead this clinical trial, investigating the potential of new weapons against cancers, testifies to our commitment at Leeds University and Leeds Teaching Hospitals NHS Trust to evaluate new innovative options that might improve the lives of our patients with cancer."

Maud Brandely, Chief Medical Officer of Transgene, added: "These very positive translational data confirm the targeted oncolytic activity and the potential of Pexa-Vec in advanced stages cancers. The observed upregulation of PD-1 and PD-L1 positive pathways strongly supports the rationale for combining Pexa-Vec with anti-PD-1 immunotherapies, which is the focus of an ongoing Phase 1/2 trial in the first-line treatment of liver cancer (HCC). These data are also crucial for our next generation of multifunctional oncolytic viruses based on our Invir.IOTM platform: this trial clearly shows that Vaccinia virus based immunotherapeutics can reach the tumor sites after i. v. administration, and selectively replicate within cancer cells. This neoadjuvant trial is the first clinical trial led by Transgene to readout this year. We look forward to announcing additional clinical results this year, not only with Pexa-Vec, but also on our four other clinical-stage immunotherapeutics."

About the Pexa-Vec "neo-adjuvant" trial:
This clinical study is aimed at evaluating the biological effects of pre-operative intravenous administration of Pexa-Vec prior to planned surgical resection of locally advanced/poor prognosis or metastatic cancers. This single center, open label, non-randomized trial recruited 9 patients including 8 evaluable patients (3 with metastatic melanoma and 5 with colorectal cancer metastases to the liver). They received a single intravenous dose of 1×109 pfu of Pexa-Vec, 14 days prior to planned surgery. Up to 6 blood samples were collected pre- and post- injection for each patient. Imaging was performed prior at baseline and within 7 days prior to surgery. Tumor tissue was collected at surgery for histologic and translational assessments.
University of Leeds is the sponsor of the trial that was supported by Transgene and run through the NIHR Clinical Research Facility at St James’ Hospital, Leeds.

The poster is available on Transgene’s website.

About Pexa-Vec
Pexa-Vec (JX594) is an oncolytic immunotherapeutic based on an oncolytic vaccinia virus armed with a GM-CSF gene that promotes an anti-tumor immune response. Pexa-Vec is designed to selectively target and destroy cancer cells through three different mechanisms of action: selectively destroy cancer cells through the direct lysis (breakdown) of cancer cells through viral replication, reduce the blood supply to tumors through vascular disruption, and stimulate the body’s immune response against cancer cells.
Pexa-Vec is currently being evaluated in a Phase 3 trial in hepatocellular carcinoma (HCC, liver cancer) in combination with sorafenib (current standard of care). Other trials evaluating the oncolytic virus in solid tumors are underway and expected to readout in 2018, including a Phase 2 trial in combination with nivolumab (HCC).
Transgene has exclusive rights to develop and commercialize Pexa-Vec for the treatment of solid tumors in Europe. Its partner SillaJen, Inc. is focused on developing Pexa-Vec for the North American market and has also granted exclusive development and commercial rights to Pexa-Vec in Hong Kong and The People’s Republic of China to Lee’s Pharmaceutical.