On September 30, 2019 Genomic Health, Inc. (NASDAQ: GHDX) reported results from a new analysis of the Trial Assigning IndividuaLized Options for Treatment (Rx), or TAILORx, which reinforce the unique value of the Oncotype DX Breast Recurrence Score test to guide the use of adjuvant chemotherapy for women with hormone receptor-positive (HR+), HER2-negative, early-stage breast cancer and identify those patients who derive a significant benefit from treatment (Press release, Genomic Health, SEP 30, 2019, View Source [SID1234539942]). The findings, published today in JAMA Oncology1 and presented at the ESMO (Free ESMO Whitepaper) 2019 Congress2, are consistent with results from the B20 trial3 and show that, in patients with high Recurrence Score results (26-100) treated with endocrine therapy plus chemotherapy, outcomes were better compared to what would be expected with endocrine therapy alone. The analysis also provides details on the outcomes of different chemotherapy regimens for the minority of patients who benefit from chemotherapy.

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"We’re pleased to see that the landmark TAILORx trial continues to receive global recognition, as evidenced by this fourth peer-reviewed publication," said Steven Shak, M.D., chief scientific officer, Genomic Health. "TAILORx established that the Oncotype DX test definitively identifies the vast majority of women with early-stage breast cancer who receive no benefit from chemotherapy and the important minority for whom chemotherapy can be life-saving. The additional insight from this new analysis is consistent with, and further supports, the conclusion that the Recurrence Score predicts which patients benefit from chemotherapy and which patients do not, giving them the standard of care they deserve."

The objective of this secondary analysis of TAILORx, the largest ever breast cancer treatment trial, sponsored by the National Cancer Institute (NCI) and led by the ECOG-ACRIN Cancer Research Group, was to evaluate clinical outcomes for patients with a high Recurrence Score result assigned to receive adjuvant chemotherapy plus endocrine therapy. In this group of 1,389 women, treated largely with standard of care taxane and/or anthracycline-containing adjuvant chemotherapy regimens, the estimated proportion free from distant recurrence at five years was about 93%, an outcome much better than expected with endocrine therapy alone in this population.

"Last year, TAILORx established the highest level of evidence and unprecedented precision supporting the use of the Oncotype DX Breast Recurrence Score test to guide adjuvant chemotherapy treatment for women with early-stage breast cancer," said lead author Joseph A. Sparano, M.D., associate director for clinical research at the Albert Einstein Cancer Center and Montefiore Health System in New York, and vice chair of the ECOG-ACRIN Cancer Research Group. "This new analysis provides the largest dataset on outcomes in patients with high Recurrence Score results, and confirms the importance of using the test to identify the patients who will receive a significant benefit from adding adjuvant chemotherapy."

The groundbreaking TAILORx results, presented during the Plenary Session at the 2018 ASCO (Free ASCO Whitepaper) Annual Meeting and simultaneously published in The New England Journal of Medicine, have elevated the Oncotype DX test to a new standard of care with increasing, and more consistent, use of the test by physicians worldwide for all medically eligible patients. The study is also having an important impact on global reimbursement of the test, most recently in Germany and Italy. Following the German Institute for Quality and Efficiency in Health Care’s (IQWiG’s) positive assessment of the TAILORx results, the German Federal Joint Committee (G-BA) issued an exclusive nationwide reimbursement decision for the Oncotype DX test. In Italy, the Lombardy Regional Authority adopted a resolution to include the test in the Regional Health Service Fees List, thereby making it available as of September 1, 2019, to eligible patients living in the region.

Over the last several months, results of the TAILORx study have also influenced positive treatment guideline updates distinguishing the Oncotype DX Breast Recurrence Score test from prognostic-only tests based on clinical evidence and the critical importance of predicting chemotherapy benefit. The updates include:

The recent update to ASCO (Free ASCO Whitepaper) guidelines, which increased the proportion of women who can be effectively treated without chemotherapy based on the Recurrence Score results, highlighting the importance of testing all medically eligible early-stage breast cancer patients.

The National Comprehensive Cancer Network (NCCN), which updated its guidelines in 2018 to categorize the Breast Recurrence Score test as the only "preferred" test for chemotherapy treatment decision-making for patients with node-negative, early-stage breast cancer. NCCN also classified the Breast Recurrence Score test as the only test that is predictive of chemotherapy benefit.

The new St. Gallen International Breast Cancer Guidelines, which recommend the Oncotype DX test to guide chemotherapy treatment use for patients with hormone-receptor positive, HER-2 negative, early-stage breast cancer with and without lymph node involvement (up to three positive nodes).

The updated ESMO (Free ESMO Whitepaper) guidelines for early-stage breast cancer, which elevated the Oncotype DX test to highest 1A level of evidence and refer to TAILORx and PlanB results, which identify groups of patients – both in the node-negative and node-positive setting – for whom chemotherapy can be safely spared.

About Oncotype DX
The Oncotype DX portfolio of breast, colon and prostate cancer tests applies advanced genomic science to reveal the unique biology of a tumor in order to optimize cancer treatment decisions. The company’s flagship product, the Oncotype DX Breast Recurrence Score test, is the only test that has been shown to predict the likelihood of chemotherapy benefit as well as recurrence in invasive breast cancer. Additionally, the Oncotype DX Breast DCIS Score test predicts the likelihood of recurrence in a pre-invasive form of breast cancer called DCIS. In prostate cancer, the Oncotype DX Genomic Prostate Score test predicts disease aggressiveness and further clarifies the current and future risk of the cancer prior to treatment intervention, and the Oncotype DX AR-V7 Nucleus Detect test helps determine which patients with metastatic castration-resistant prostate cancer (mCRPC) are resistant to androgen receptor (AR)-targeted therapies. The Oncotype DX AR-V7 Nucleus Detect test is performed by Epic Sciences at its centralized, CLIA-certified laboratory in San Diego and offered exclusively by Genomic Health. With more than 1 million patients tested in more than 90 countries, the Oncotype DX tests have redefined personalized medicine by making genomics a critical part of cancer diagnosis and treatment. To learn more about Oncotype DX tests, visit www.OncotypeIQ.com, www.MyBreastCancerTreatment.org or www.MyProstateCancerTreatment.org.

On September 30, 2019 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage, Precision Cancer Medicine oncology therapeutics company developing drugs that target cell division (mitosis), for the treatment of various cancers including leukemia, prostate and colorectal, reported that results from the Company’s Phase 1b/2 study of onvansertib in patients with relapsed/refractory acute myeloid leukemia (AML) were presented in an oral plenary session at the 2019 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Conference in Barcelona, Spain, on Saturday, September 28th (Press release, Trovagene, SEP 30, 2019, View Source [SID1234539941]). The presentation highlighted the favorable safety profile and clinical efficacy of onvansertib, as well as correlative biomarker data from the recently completed Phase 1b trial.

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The oral presentation at ESMO (Free ESMO Whitepaper) is available for download from the Scientific Presentations page on the Trovagene website at View Source

"These data from this ongoing clinical trial in patients with relapsed/refractory AML support that the combination of onvansertib with either low dose cytarabine or decitabine appear to be feasible, safe and well tolerated up through the 60mg/m2 dose of onvansertib," said Dr. Amer Zeidan, lead investigator and assistant professor of Medicine at the Yale School of Medicine, and Hematology expert at Yale Cancer Center. "While the recently completed dose escalation part of the study focused on evaluating the safety of the combinations, we see evidence of clinical activity, particularly with onvansertib in combination with decitabine. We hope to better understand the efficacy profile of this combination as we go into the Phase 2 expansion part of the trial."

"We continue to be encouraged by our biomarker data which indicates a correlation between biomarker positive patients and their response to treatment with onvansertib," said Dr. Mark Erlander, Chief Scientific Officer of Trovagene. "As we move forward, we plan to further develop the biomarker assay to enable us to proactively identify patients who are most likely to respond to treatment."

Oral Presentation Highlights

Background:

Onvansertib is an oral, highly-selective Polo-like Kinase 1 (PLK1) inhibitor with a half-life of ~24 hours
PLK1 inhibition by onvansertib, assessed via a simple blood test and shown as changes in the phosphorylation of its direct substrate, the translational controlled tumor protein, TCTP, is a biomarker for identifying patients most likely to respond to treatment
Patients eligible for enrollment in the Phase 1b/2 trial are treatment naïve and not candidates for induction therapy or have relapsed/refractory disease to up to 3 prior regimens (Phase 1b) and 1 prior regimen (Phase 2), including those resistant to treatment with venetoclax
Treatment Summary as of June 1, 2019

Safety and Tolerability:

Treatment was well tolerated with no unexpected toxicities reported
No dose limiting serious adverse events or trial related deaths were attributed to onvansertib (Grade 3 or 4 adverse events possible related to onvansertib included 10 (30%) hematologic and 1 (3%) non-hematologic)
The maximum tolerated dose (MTD) was not reached through onvansertib dose level of 60mg/m2, but was subsequently achieved at the 90mg/m2 dose level
Preliminary Efficacy:

In the onvansertib plus decitabine arm, of the 12 patients evaluable for efficacy at onvansertib doses ranging from 12mg/m2 to 40mg/m2, 3 patients achieved the primary efficacy endpoint of objective response (2 CRs – 1 at onvansertib 27mg/m2, 1 at onvansertib 40mg/m2 and 1 CRi at onvansertib 27mg/m2)
In the onvansertib plus low-dose cytarabine arm, of the 12 patients evaluable for efficacy at onvansertib doses ranging from 12mg/m2 to 40mg/m2, 1 patient achieved the primary efficacy endpoint of objective response (CRi at onvansertib 40mg/m2); LDAC arm was discontinued following completion of onvansertib 60mg/m2 cohort
Phase 1b has been successfully completed and the Phase 2 open-label, single-arm trial is enrolling patients for treatment with the recommended Phase 2 dose (RP2D) of onvansertib at 60mg/m2 in combination with decitabine to continue assessing safety and efficacy
Biomarker Analysis:

Of the 24 evaluable patients, 9 (38%) were biomarker positive across both arms
There is a strong correlation between biomarker positive patients and response to treatment with onvansertib; 6 of 9 biomarker positive patients had a decrease in bone marrow blasts of ≥ 50%, versus 1 of 11 in the biomarker negative patients
Among the 4 patients with CR (CR + CRi) 3 were biomarker positive and 1 was borderline biomarker positive
Further biomarker validation is continuing including development of a second-generation assay that is more sensitive and quantitative
About the Phase 2 Clinical Trial of Onvansertib in AML

The Phase 2 AML trial (NCT03303339) of onvansertib in combination with decitabine will enroll 32 patients who are either treatment naïve and not candidates for induction therapy or who have relapsed disease after treatment with one prior regimen. Patients will receive onvansertib, administered orally, on days 1 through 5 of each 21-28-day cycle in combination with decitabine. The primary efficacy endpoint of objective response (CR + CRi) will be assessed in patients who complete at least 1 cycle of treatment.

About Onvansertib

Onvansertib is a first-in-class, third-generation, oral and highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK1) enzyme, which is over-expressed in multiple cancers including leukemias, lymphomas and solid tumors. Onvansertib targets the PLK1 isoform only (not PLK2 or PLK3), is orally administered and has a 24-hour half-life with only mild-to-moderate side effects reported. Trovagene believes that targeting only PLK1 and having a favorable safety and tolerability profile, along with an improved dose/scheduling regimen will significantly improve on the outcome observed in previous studies with a former panPLK inhibitor in AML.

Onvansertib has demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukemias, lymphomas and solid tumor cancers, including irinotecan, FLT3 and HDAC inhibitors, taxanes and cytotoxins. Trovagene believes the combination of onvansertib with other compounds has the potential to improve clinical efficacy in acute myeloid leukemia (AML), metastatic castration-resistant prostate cancer (mCRPC), non-Hodgkin lymphoma (NHL), colorectal cancer and triple-negative breast cancer (TNBC), as well as other types of cancer.

Trovagene has three ongoing clinical trials of onvansertib: A Phase 2 trial of onvansertib in combination with Zytiga (abiraterone acetate)/prednisone in patients with mCRPC who are showing signs of early progressive disease (rise in PSA but minimally symptomatic or asymptomatic) while currently receiving Zytiga (NCT03414034); a Phase 1b/2 Study of onvansertib in combination with FOLFIRI and Avastin for second-line treatment in patients with mCRC with a KRAS mutation (NCT03829410); and a Phase 1b/2 clinical trial of onvansertib in combination with low-dose cytarabine or decitabine in patients with relapsed or refractory AML (NCT03303339). Onvansertib has been granted orphan drug designation by the FDA in the U.S. and by the EC in the European Union for the treatment of patients with AML.

Trovagene licensed onvansertib (also known as NMS-1286937 and PCM-075) from Nerviano Medical Sciences (NMS), the largest oncology-focused research and development company in Italy, and a leader in protein kinase drug development. NMS has an excellent track record of licensing innovative drugs to pharma/biotech companies, including Array (recently acquired by Pfizer), Ignyta (acquired by Roche) and Genentech.

On September 30, 2019 Oragenics, Inc. (NYSE American:OGEN) ("Oragenics"), a leader in the development of novel antibiotics against infectious diseases and effective treatments for oral mucositis, reported initial data from its ongoing Phase 2, placebo-controlled, clinical trial of AG013 in oral mucositis presented in a poster session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2019 in Barcelona, Spain (Press release, Oragenics, SEP 30, 2019, View Source [SID1234539940]).

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Titled, "Severe oral mucositis (SOM) mitigation by genetically modified Lactococcus lactis bacteria (LLB) producing human trefoil factor 1 (hTFF1; AG013) in patients being treated with concomitant chemoradiation (CRT) for oral and oropharyngeal cancers (OCOPC)," was presented at the ESMO (Free ESMO Whitepaper) Congress 2019 in Barcelona, Spain. The poster can be found under the "Presentations" tab in the "News and Media" section of the Company’s website, located at www.oragenics.com.

The poster presentation describes the methods and initial blinded results from the ongoing Phase 2 clinical trial for the Company’s lead oral mucositis product candidate, AG013. The ongoing Phase 2 clinical trial is a double-blind, placebo-controlled, two-arm, multi-center trial, in which approximately 200 patients will be randomized in a 1:1 ratio to receive either AG013 or placebo three times daily following meals, beginning on the first day of chemoradiation therapy and continuing through the course of cancer treatment. The purpose of this Phase 2 clinical study, (NCT03234465), is to evaluate the efficacy (preventing the occurrence and shortening the duration of SOM), safety, and tolerability of a convenient topically administered rinse of AG013 compared to a placebo for reducing the incidence and severity of oral mucositis in patients undergoing traditional chemoradiation for the treatment of head and neck cancer. The initial data, submitted in the abstract, reflects the results for 42 of the 71 enrolled and randomized patients across 48 study sites and demonstrates that in the blinded, combined placebo and active treatment groups, there was sufficient evidence of efficacy and safety to continue the study.

Additional data accumulated since poster submission, indicates the blinded efficacy evaluation, which included any patient with SOM after week one of treatment and those receiving a cumulative dose of 55 Gy (week 6 of treatment), demonstrated an overall SOM incidence of 47%, which is lower than would be expected based on historical data in the head and neck cancer population receiving this chemoradiation regimen. The overall rate of SOM was reported in only 13.1 % (110 of 842) of evaluable visits. The overall safety profile is consistent with those adverse events that normally occur in cancer patients receiving chemoradiation therapy. As a reminder, the study remains blinded and individual treatment responses remain to be identified. The lead author for the poster presentation is Suraj Singh, M.D., of the MultiCare Regional Cancer Center in Tacoma, Washington.

Alan Joslyn, President & CEO of Oragenics, Inc. said, "As we recently announced, we are more than 75 percent enrolled in this study, and we continue to be encouraged by both the pace of enrollment and the overall clinical results as reported in this poster presentation. While it remains difficult to comment on efficacy outcomes based on these data, we are pleased with the safety profile we are seeing in the study. Due to the high incidence of SOM in head and neck cancer patients, and the blinded results seen to date, we maintain the belief that this compound will provide a convenient meaningful therapeutic benefit for these patients with limited treatment alternatives and no therapies available for prevention of their oral mucositis."

About Oral Mucositis

Oral mucositis is currently one of the most common and debilitating complications of cancer chemo- and radiation therapy. The condition is caused by the breakdown of the mucosal lining in the oral cavity resulting in the formation of painful mouth ulcers. When these mouth ulcers progress to World Health Organization (WHO) grade 3 and 4, patients by definition, have their ability to eat (grade 3) and drink (grade 4) impacted resulting in emergency room visits or hospitalization in order to provide pain control and nutritional support. During these periods, patients run the risk of interruption of their chemo- and radiation therapies with the potential risk of negative cancer treatment outcomes. The incidence of SOM is approximately 70% in oropharyngeal cancer patients.

About AG013

AG013, which has been granted Fast Track designation with the U.S. Food and Drug Administration and orphan drug status in Europe, is an ActoBiotics therapeutic candidate formulated to deliver the therapeutic molecule Trefoil Factor 1 to the mucosal tissues in the oral cavity in a convenient oral rinsing solution. Trefoil Factors are a class of peptides involved in the protection of gastrointestinal tissues against mucosal damage and play an important role in subsequent repair. The compound was designed by the company’s strategic partner, ActoBio Therapeutics, Inc., a wholly-owned subsidiary of Intrexon Corporation (NYSE:XON).

On September 30, 2019 Idera Pharmaceuticals, Inc. (NASDAQ: IDRA) reported the initiation of a phase 2 trial, ILLUMINATE-206 which will evaluate tilsotolimod, a toll-like receptor 9 (TLR9) agonist, in combination with nivolumab, a programmed death receptor-1 (PD-1) blocking antibody, and ipilimumab, a human cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking antibody for the treatment of solid tumors (Press release, Idera Pharmaceuticals, SEP 30, 2019, View Source [SID1234539939]).

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The primary objective of this phase 2, open-label, global, study is to demonstrate efficacy (measured by overall response rate [ORR] based on RECIST v.1.1). Secondary and exploratory objectives include safety, tolerability, immunogenicity and translational data evaluations.

The initial cohort of the trial will be patients with immunotherapy-naive Microsatellite Stable Colorectal Cancer (MSS-CRC). The second planned cohort of ILLUMINATE-206 will focus on treating patients with anti-PD(L)-1 refractory Squamous Cell Carcinoma of the Head and Neck (RM-SCCHN), which will initiate in the fourth quarter of this year.

"Initiation of this Phase 2 study is an important step toward understanding the broader applications of tilsotolimod," stated Elizabeth A. Tarka, M.D., F.A.C.C., Idera’s Chief Medical Officer. "Demonstrating the potential benefit of tilsotolimod in patients with specific solid tumors where the disease setting under investigation have no approved immunotherapies, would be a significant contribution to the treatment paradigm."

The basis for this trial is supported by data generated from the ILLUMINATE-101 trial, which studied intratumoral tilsotolimod monotherapy in 45 evaluable patients with a variety of solid tumor types in which 33% (n=15) achieved stable disease. Translational research in ILLUMINATE-101, demonstrated that tilsotolimod increased dendritic cell activation and upregulated MHC class II and IFN-α signaling which suggests improved antigen presentation. These findings are consistent with those observed in the ILLUMINATE-204 trial in anti-PD-1 refractory metastatic melanoma patients. Therefore, the mechanism of action for tilsotolimod may be tumor-type agnostic and potentially beneficial in combination with checkpoint modulation in a variety of tumor types.

A poster presentation from ILLUMINATE-101 is being presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress in Barcelona, Spain today and can be found in the Key Publications section of Idera’s Corporate website, www.iderapharma.com.

On March 11, 2019, Idera and Bristol-Myers Squibb (BMS) entered into a clinical trial collaboration and supply agreement in which BMS has agreed to supply YERVOY* (ipilimumab) and OPDIVO (nivolumab) for no charge for use in ILLUMINATE-206.

On September 30, 2019 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that Michael Nally, Chief Marketing Officer for Merck, is scheduled to present during a fireside chat at the Cantor Fitzgerald 2019 Annual Global Healthcare Conference in New York on Wednesday, Oct. 2, at 2:25 p.m. EDT (Press release, Merck & Co, SEP 30, 2019, View Source [SID1234539938]).

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Investors, analysts, members of the media and the general public are invited to listen to a live audio webcast of the presentation at View Source