On April 1, 2020 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage, oncology therapeutics company developing onvansertib for the treatment of various cancers including colorectal, prostate and leukemia, reported that its Phase 1b/2 clinical trial of onvansertib in combination with standard-of-care FOLFIRI/Avastin (bevacizumab) for second-line treatment of patients with KRAS-mutated mCRC, will be featured in a presentation at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting to be held from May 29 – June 2 (Press release, Trovagene, APR 1, 2020, View Source [SID1234556073]).

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There is a significant, unmet medical need to develop a safe and effective second-line treatment option for patients with KRAS-mutated mCRC. Currently available treatments have limited efficacy with only a 4% response rate and a median of 5.5 months progression-free survival (PFS). Other compounds currently in clinical development that target KRAS-mutated cancers have shown minimal activity in mCRC.

Data presented at the ASCO (Free ASCO Whitepaper)-GI meeting in late January showed the effectiveness of onvansertib against all prevalent KRAS mutations associated with mCRC by quantitative decreases in the plasma KRAS mutation levels in treated patients within the first cycle of treatment. Subsequent radiographic scans performed at 8 and 16 weeks confirmed efficacy by measurable shrinkage of tumors in all patients.

"We are excited to have our abstract accepted for presentation at the prestigious ASCO (Free ASCO Whitepaper) annual meeting," said Dr. Thomas Adams, Chief Executive Officer and Chairman of Trovagene. "Despite more than 30 years of intensive efforts, anti-KRAS therapies have remained elusive, and currently there are no drugs effectively targeting a broad spectrum of KRAS mutations. We believe onvansertib has the potential to provide a substantially improved treatment option for second-line treatment of patients with KRAS-mutated mCRC."

About the Phase 1b/2 Trial of Onvansertib in Metastatic KRAS-mutated Colorectal Cancer

The trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second‑Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation (NCT03829410), will evaluate the safety and efficacy of onvansertib in combination with standard-of-care FOLFIRI and Avastin (bevacizumab). Up to 44 patients, with a confirmed KRAS mutation, metastatic and unresectable disease, who have failed or are intolerant of treatment with FOLFOX (fluoropyrimidine and oxaliplatin) with or without Avastin (bevacizumab), will be enrolled. The trial is being conducted at two prestigious cancer centers: USC Norris Comprehensive Cancer Center and The Mayo Cancer Center.

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 April 1, 2020 Sysmex reported The "Prospective Study to Assess the Feasibility and Clinical Utility of Comprehensive Genomic Profiling at the Time of Initial Treatment in Patients with Solid Tumors" (the "Study"), which uses the OncoGuide NCC Oncopanel System1 (the "System", generic name: mutation analysis set for cancer genome profiling) developed through collaboration between the National Cancer Center (Location: Tokyo, Japan; President: Hitoshi Nakagama) and Sysmex Corporation (HQ: Kobe, Japan; Chairman and CEO: Hisashi Ietsugu), has been applied as Advanced Medical Care2 on April 1, 2020 (Press release, Sysmex, APR 1, 2020, View Source [SID1234556072]). The start date of this test will be announced on the website as soon as preparations at the National Cancer Center are completed. (View Source)

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The System analyzes genetic alterations in cancer-specific genes in patients with solid tumors and provides the cancer genomic profile of the tumor to help determine the treatment strategy, including accurate diagnosis and the selection of anti-cancer drugs. Currently, the System is covered by the National Health Insurance (NHI) in patients who have already undergone the standard treatment. Personalized genomic medicine based on cancer genomic profiling from an early phase at the time of initial treatment could provide the patients with more opportunities for appropriate treatment, including matched therapy. However, the feasibility and clinical utility of the System at the time of initial treatment remains unclear.

On April 1, 2020, the "Prospective Study to Assess the Feasibility and Clinical Utility of Comprehensive Genomic Profiling at the Time of Initial Treatment in Patients with Solid Tumors" has been applied as Advanced Medical Care. The National Cancer Center will announce the start date of this test at the National Cancer Center Hospital on its website as soon as the National Cancer Center is ready. (View Source).

The Study will include patients with six types of advanced or recurrent solid tumors, which could be treated with medication, including non-small-cell lung cancer, gastric cancer, colon cancer, breast cancer, pancreatic cancer, and biliary tract cancer (a total of 200 cases). We will evaluate whether personalized genomic medicine based on cancer genome profiling by the System at the time of initial treatment results in more opportunities of matched therapies compared to after standard treatment.

All collected samples will be analyzed at the Innovation Genome Center (Kawasaki Office) of RIKEN GENESIS Co., Ltd. (HQ: Tokyo, Japan; President and CEO: Naoto Kondo), a Sysmex subsidiary which provides lab assay services for gene analysis.

The National Cancer Center, Sysmex and RIKEN GENESIS will contribute to the implementation and development of personalized genomic medicine in Japan by providing high-value testing and diagnostic technologies for cancer patients.

Product Overview

Generic name: Gene mutation analysis set (for use in cancer genome profiling)

Name: OncoGuide NCC Oncopanel System (medical equipment production sales authorization number: 23000BZX00398000)

Target institutions: Medical institutions that have in place diagnostic systems appropriate for cancer genome profiling Target market: Japan

References

Press release dated December 25, 2018: "Sysmex Receives Manufacturing and Marketing Approval to Use the OncoGuide NCC Oncopanel System in Cancer Genome Profiling" View Source

Press release dated May 31, 2019: "The OncoGuide NCC Oncopanel System Receives Insurance Coverage for Use in Cancer Genome Profiling" View Source

Terminology
1 OncoGuide NCC Oncopanel System:
On December 25, 2018, Sysmex received manufacturing and marketing approval for the System as Japan’s first system for cancer genome profiling. This was also the first such system to be covered under the NHI, as of June 1, 2019.
The NHI coverage for D006-19 cancer genome profiling using the System includes patients with solid tumors for which no standard treatment exists and patients with solid tumors confirmed to have advanced locally or metastasized (including patients for which treatment is expected to conclude). Coverage is limited to cases in which the attending physician determines the potential for applying chemotherapy following this testing is high based on chemotherapy guidelines from related societies and the patient’s general status and organ function. The objective of Advanced Medical Care is to assess utility at the time of initial treatment.

2 Advanced Medical Care:
Refers to advanced healthcare technologies that have been approved by Japan’s Minister of Health, Labour and Welfare but are not yet covered by healthcare insurance. Based on a Fundamental Accord in December 2004 between the Minister of Health, Labour and Welfare; the Cabinet Officer Minister of State in Charge of Special Missions (regulatory reform, industrial revitalization); the minister in charge of administrative reform; and the Minister in charge of Special Zones for Structural Reform and Regional revitalization, this system was approved in combination with healthcare insurance coverage from the perspective of ensuring the safety of patients in Japan, preventing patient burdens from increasing, expanding patient choices, and increasing convenience.

On April 1, 2020 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, reported that its partner, BeiGene, Ltd., has dosed the first patient in a two-arm Phase 1b/2 trial evaluating Zymeworks’ HER2-targeted bispecific antibody ZW25 in combination with chemotherapy as a first-line treatment for patients with metastatic HER2-positive breast cancer and in combination with chemotherapy and BeiGene’s PD-1-targeted antibody tislelizumab as a first-line treatment for patients with metastatic HER2-positive gastroesophageal adenocarcinoma (GEA) (Press release, Zymeworks, APR 1, 2020, View Source [SID1234556071]). Zymeworks will receive a payment under its collaboration with BeiGene as a result of the achievement of this development milestone.

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"To date, ZW25 has demonstrated promising activity in late-stage, treatment-refractory HER2-expressing tumors. This new clinical trial provides a unique opportunity to evaluate the additional potential benefit of ZW25 in first-line metastatic breast tumors which have not developed resistance to multiple HER2-targeted therapeutics," said Diana Hausman, M.D., Chief Medical Officer at Zymeworks. "In addition, the GEA arm of this trial complements our ongoing Phase 2 trial of ZW25 plus chemotherapy in first-line GEA, and we are excited to examine possible synergies between ZW25 and BeiGene’s PD-1 inhibitor tislelizumab. We look forward to the results of these trials, which have the potential to further expand the population of patients who may benefit from ZW25."

"Through this collaboration with Zymeworks, our broad development program for tislelizumab is expanding into HER2-expressing tumors as a potential first-line treatment," said Lai Wang, Ph.D., Senior Vice President, Head of Global Research and APAC Clinical Development at BeiGene. "ZW25 has demonstrated appealing clinical activity against HER2-positive tumors, and we are excited to gain additional understanding of its use as a monotherapy and in combinations as well."

This Phase 1b/2 clinical trial is a multicenter, open-label, two-arm study (NCT04276493). Arm one of the trial will evaluate the safety, tolerability, and preliminary antitumor activity of ZW25 in combination with docetaxel in patients with metastatic HER2-positive breast cancer. The second arm of the trial will evaluate the safety, tolerability, and preliminary antitumor activity of ZW25 in combination with tislelizumab and chemotherapy in patients with HER2-positive GEA, including gastric and gastroesophageal junction (GEJ) adenocarcinomas.

An ongoing Phase 1 trial is evaluating the safety and antitumor activity of ZW25 as a single agent and in combination with chemotherapy in HER2-expressing cancers that have progressed after prior standard of care treatments, including HER2-targeted agents (Phase 1: NCT02892123). ZW25 is also being evaluated in a Phase 2 trial in first-line HER2-positive GEA in combination with standard of care chemotherapy (Phase 2: NCT03929666) as well as in combination with the oral CDK4/6 inhibitor palbociclib (Ibrance, Pfizer) and fulvestrant in advanced HER2-positive, HR-positive breast cancer (Phase 2: NCT04224272). Zymeworks, in collaboration with BeiGene, also plans to initiate registration-enabling studies of ZW25 in patients with previously treated HER2-positive biliary tract cancer and develop ZW25 as a potential first-line treatment for patients with HER2-positive GEA.

About ZW25

ZW25 is being evaluated in multiple Phase 1 and Phase 2 clinical trials globally. It is a bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging antitumor activity in patients. Zymeworks is developing ZW25 as a targeted treatment option for patients with solid tumors that express HER2. The FDA has granted two Fast Track Designations to ZW25, one as a single agent for refractory biliary tract cancer and one in combination with standard of care chemotherapy, for first-line GEA. ZW25 has also received Orphan Drug Designations for the treatment of biliary tract, gastric, and ovarian cancers.

About the Zymeworks-BeiGene Collaboration

In November 2018, Zymeworks and BeiGene entered into license and collaboration agreement in which BeiGene was granted an exclusive license for the research, development and commercialization of ZW25 and ZW49 in Asia (excluding Japan), Australia, and New Zealand. The companies are collaborating on joint global development for selected indications, with the goal of developing ZW25 and ZW49 worldwide across multiple HER2-expressing cancers and lines of therapy.

On April 1, 2020 Veracyte, Inc. (Nasdaq: VCYT) reported results of a study that identified over 100 novel or rare NTRK, ALK, RET and BRAF fusions in fine needle aspiration (FNA) samples of patients undergoing evaluation for thyroid cancer (Press release, Veracyte, APR 1, 2020, View Source [SID1234556070]). These gene fusions – 70 of which are previously unreported – may potentially be targeted with specific kinase inhibitor drugs that are currently available or in development for use in thyroid cancer patients. Veracyte also announced that it has launched an expanded version of its Afirma Xpression Atlas (XA) test, which uses RNA sequencing to detect gene alterations – including these novel or rare fusions – at the time of diagnosis.

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The new data are featured in an abstract that was accepted for an oral presentation this week at ENDO 2020*, the annual meeting of The Endocrine Society. The study was one of two Afirma XA-related abstracts accepted for the meeting.

For the new study, researchers performed RNA whole-transcriptome sequencing on over 37,000 thyroid nodule FNA samples whose cytopathology results were either indeterminate (Bethesda III/IV) or suspicious for cancer (Bethesda V/VI). They found 104 novel or rare gene fusions – 7 NTRK1/3, 8 ALK, 17 RET and 72 BRAF – none of which were previously reported for thyroid cancer in The Cancer Genome Atlas (TCGA) program, a United States government catalogue of gene alterations associated with cancer. The authors subsequently examined over 50,000 FNA samples that had undergone testing with Veracyte’s Afirma Genomic Sequencing Classifier (GSC) and found that none of the novel or rare gene fusions were detected among those deemed benign. NTRK, ALK, RET and BRAF fusions, including those in the new study, were identified in 3.2 percent of the 16,594 Bethesda III/IV samples that were deemed suspicious for cancer by the Afirma GSC and in 8.0 percent of the 1,692 Bethesda V/VI samples.

"Identification of receptor tyrosine kinase fusions is important because they are potential targets for small molecule inhibitors that are now FDA-approved or in clinical trials to treat advanced thyroid cancers," said Lori J. Wirth, M.D., medical director of the Center for Head and Neck Cancers at Massachusetts General Hospital and lead author of the study. "By examining a large cohort of patients with RNA whole-transcriptome sequencing, we identified potentially actionable RTK fusions in thyroid nodules beyond those described in TCGA, which may have an impact on treatment decisions for many patients."

Veracyte also announced the introduction of its expanded Afirma XA, which provides physicians with additional gene alteration content – including the novel or rare NTRK, ALK, RET and BRAF fusions from the new study – to further inform surgery and treatment decisions for patients with suspected or confirmed thyroid cancer. The Afirma XA utilizes RNA sequencing on the same FNA sample used for Afirma GSC testing. Compared to the original gene alteration panel, the expanded Afirma XA now reports 905 DNA variants (versus 761) and 235 RNA fusion partners (versus 130) in 593 genes (versus 511).

"By including additional gene fusion data that can potentially be targeted with new therapies, the expanded Afirma XA provides physicians with even more powerful information with which to guide surgery and treatment decisions in their patients with thyroid cancer," said Richard T. Kloos, M.D., senior medical director of endocrinology at Veracyte. "Importantly, the Afirma XA provides this information pre-operatively through a minimally invasive FNA sample."

In the second Afirma XA-focused abstract accepted for ENDO 2020 – as a poster presentation – researchers reported on the positive predictive value of TP53 gene variants among thyroid nodules deemed suspicious for cancer by the Afirma GSC following indeterminate cytopathology results.

About Afirma

The Afirma Genomic Sequencing Classifier (GSC) and Xpression Atlas provide physicians with a comprehensive solution for thyroid nodule diagnosis. The Afirma GSC was developed with RNA whole-transcriptome sequencing and machine learning and helps identify patients with benign thyroid nodules among those with indeterminate cytopathology results in order to help patients avoid unnecessary diagnostic thyroid surgery. For those with suspected thyroid cancer, the Afirma Xpression Atlas provides physicians with genomic alteration content from the same fine needle aspiration samples that are used in Afirma GSC testing and may help physicians decide with greater confidence on the surgical or therapeutic pathway for their patients.

On April 1, 2020 Forbius, a clinical-stage protein engineering company that develops biotherapeutics to treat cancer and fibrosis, reported that Ilia Tikhomirov, CEO of Forbius, will present a corporate update at the upcoming Solebury Trout Virtual Investor Conference (Press release, Forbius, APR 1, 2020, View Source [SID1234556068]).

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The 25 minute presentation includes an interactive Q&A with participants prompted to submit questions electronically. Details are as follows:

Date/Time:

Thursday, April 2, 2020, at 2:30p.m. EDT

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