On January 4, 2019 Aura Biosciences, a leader in the development of novel targeted therapies in ocular oncology, reported that it has received written confirmation from the U.S. Food and Drug Administration (FDA) regarding agreement on the design of its Phase 3 registration trials designed to evaluate light-activated AU-011 for the treatment of patients with choroidal melanoma (Press release, Aura Biosciences, JAN 4, 2019, View Source [SID1234532454]). This written confirmation is the result of successful outcome of an "End of Phase 2" meeting with the FDA.

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The STARBRIGHT registration program will consist of two small identical clinical trials designed to assess the safety and efficacy of AU-011 versus sham control for the treatment of patients with small choroidal melanoma and high risk indeterminate lesions. Both trials, which will be titled STARBRIGHT1 and STARBRIGHT3, will be global, multicenter, randomized and masked, and will be conducted in parallel. The primary endpoint will be comprised of a combination of tumor control and vision preservation.

In addition to the design of the Phase 3 trials, the FDA agreed with Aura’s proposed safety database. The FDA also agreed that no further non-clinical studies are needed.

"We are pleased to have received such clear guidance from the FDA with respect to the Phase 3 STARBRIGHT program to be able to meet the scientific and regulatory requirements for marketing approval in the U.S." said Elisabet de los Pinos, Ph.D., Chief Executive Officer of Aura.

The currently available treatments for choroidal melanoma come with the risk of severe vision loss, especially for patients with melanomas located close to the fovea or optic disk. The ongoing Phase 1b/2 study with light-activated AU-011 has shown that the drug was well-tolerated, with clear evidence of tumor control and preservation of visual acuity at long term follow up.

"We believe that a minimally invasive, non-radiation-based treatment option that enables early intervention while preserving vision has the potential to transform the therapeutic landscape for this difficult to treat, often deadly form of melanoma," said Cadmus Rich, M.D., Chief Medical Officer of Aura. "Overall, the meeting removed any remaining uncertainty on the regulatory path to approval and highlighted FDA’s commitment to guide Aura toward a potential first drug approved for patients with this highly unmet medical need."

About Choroidal Melanoma

Choroidal melanoma is a rare and aggressive type of eye cancer. Choroidal melanoma is the most common primary ocular tumor and develops in the uveal tract of the eye. No targeted therapies are available at present, and current radiotherapy treatments can be associated with severe visual loss and other long-term sequelae such as dry eye, glaucoma, cataracts and radiation retinopathy. The most common current treatment is plaque radiotherapy, which involves surgical placement of a radiation device on the exterior of the eye over the tumor. The alternative is enucleation, or total surgical removal of the eye. Choroidal melanoma metastasizes to the liver in about 40-50 percent of cases in the long term (source: OMF), and only 15 percent of patients whose melanoma has metastasized survive beyond five years after diagnosis (source: ACS).

About Light-Activated AU-011

AU-011 is a first-in-class targeted therapy in development for the primary treatment of choroidal melanoma. The therapy consists of proprietary viral-like particle bioconjugates (VPB) that are activated with an ophthalmic laser. The VPBs bind selectively to unique receptors on cancer cells in the eye and are derived from technology originally pioneered by Dr. John Schiller of the Center for Cancer Research at the National Cancer Institute (NCI), recipient of the 2017 Lasker-DeBakey Award. Upon activation with an ophthalmic laser, the drug rapidly and specifically disrupts the cell membrane of tumor cells while sparing key eye structures, which may allow for the potential of preserving patients’ vision and reducing other long-term complications of radiation treatment. AU-011 can be delivered using equipment commonly found in an ophthalmologist’s office and does not require a surgical procedure, pointing to a potentially less invasive, more convenient therapy for patients and physicians. AU-011 for the treatment of choroidal melanoma has been granted orphan drug and fast track designations by the U.S. Food and Drug Administration and is currently in clinical development.

On January 4, 2019 Sangamo Therapeutics, Inc. (NASDAQ: SGMO) reported that Sandy Macrae, CEO of Sangamo, will present a corporate overview at the 37th Annual J.P. Morgan Healthcare Conference on Wednesday, January 9th at 11:30 a.m. PT in San Francisco (Press release, Sangamo Therapeutics, JAN 4, 2019, View Source [SID1234532471]). Dr. Macrae’s presentation will be followed by a separate Q&A session starting at 12:00 p.m. PT.

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The presentation and Q&A session will be webcast live and may be accessed via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations. The presentation will be archived on the Sangamo website for two weeks after the event.

On January 4, 2019 PierianDx, a leading clinical genomics informatics company, reported a strategic, non-exclusive, multi-year partnership with Illumina, Inc. to provide a variant interpretation and reporting solution based on PierianDx’s Clinical Genomics Workspace platform and Clinical Genomics Knowledgebase for select Illumina oncology products (Press release, PierianDx, JAN 4, 2019, View Source [SID1234554038]). Under the agreement, PierianDx and Illumina will offer customers the option of informatics capabilities for Illumina oncology products, including Illumina’s TruSight Tumor 170 and TruSight Oncology 500, which are currently intended for research use only (RUO). The partnership extends to support Illumina’s future oncology in vitro diagnostic (IVD) offerings. Advancing cancer diagnostics and making targeted therapeutics more accessible to healthcare systems, laboratories, and patients worldwide is a key focus of both parties.

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"Accessibility of genomic testing in clinical oncology is critical to realizing the promise of immuno- and targeted therapies and personalized medicine," states Rakesh Nagarajan, MD, PhD, Founder and Executive Chairman, PierianDx. "Today, few laboratories have the ability to offer comprehensive tumor profiling because of the complexities associated with validating large NGS assays and interpreting genomic results. This agreement between PierianDx and Illumina has the potential to provide laboratories clinically-optimized solutions that may accelerate assay validation and deployment and simplify genomic interpretation."

"The combination of Illumina’s comprehensive tumor profiling assays with Pierian Dx’s variant interpretation and reporting solutions will provide customers with a seamless experience," said Garret Hampton, PhD, Executive Vice President of Clinical Genomics at Illumina.

"PierianDx is thrilled to receive this substantial validation of our genomics Software as a Service (‘SaaS’) platform by a global leader in our space. Our relationship with Illumina will allow us to greatly accelerate our U.S. and international strategic plans as we seek to be the wisdom behind every genomics report," said Michael L. Sanderson, CEO of PierianDx.

Under the agreement Illumina and its affiliates will be responsible for the distribution of the RUO oncology products and packaged solutions. Laboratories that purchase the RUO products from Illumina will have an option to receive from PierianDx standardized reporting, driven by professional guidelines for streamlined case review and sign-out. In addition, laboratories who purchase the bundled RUO oncology product with the PierianDx informatics solution will receive access to PierianDx’s Clinical Genomics Workspace for analysis, interpretation, and reporting of genomic results. Laboratories will also have the opportunity to engage PierianDx for additional services such as genomic interpretation, medical sign-out, and electronic medical record integration.

On January 4, 2019 ViewRay, Inc. (Nasdaq: VRAY) reported the enrollment of the first patient in the Stereotactic MRI-guided On-table Adaptive Radiation Therapy (SMART) Trial, a multi-center, prospective clinical trial for locally advanced or borderline pancreatic cancer (Press release, ViewRay, JAN 4, 2019, View Source [SID1234532472]). The trial will explore the clinical benefits of precise, high dose radiation therapy enabled by MR-guidance combined with daily on-table adaptation in the treatment of pancreatic cancer.

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Retrospective analysis of precise, high-dose MR-guided radiation therapy delivered using adaptive dose planning has shown promising results with locally advanced pancreatic cancer, suggesting the potential for improving overall survival relative to patients receiving lower radiation doses, without increasing the rate of serious gastrointestinal toxicity. The compelling nature of the retrospective data prompted the SMART trial, aimed at investigating in a controlled, prospective manner, the robustness of this outcome and tracking quality of life over a 5-year trial period.

"High-definition MR and daily treatment plan adaptation allow us to deliver ablative radiation doses safely to pancreatic cancer patients for the first time ever," said Parag Parikh, M.D., co-PI of the study and Director of GI Radiation Oncology and MR-Guided Radiation Therapy at the Henry Ford Cancer Institute in Detroit. "Through the SMART trial, we will build upon the promising experience from UCLA, Washington University, Amsterdam UMC, University of Miami and University of Wisconsin by further exploring MRIdian’s impact on associated toxicity, local control and patient outcomes in pancreatic cancer at multiple institutions around the world."

The SMART trial is the first prospective, multi-institutional study to deliver ablative doses of radiation to pancreatic cancer patients. It aims to enroll 133 participants with borderline resectable or inoperable locally advanced pancreatic cancer. In the single-arm study, participants will receive radiation therapy at a dose of 50 Gray in 5 fractions (treatment sessions) using ViewRay’s MRIdian. On-table adaptive re-planning will be used when clinically indicated. In all patients, real-time MRI imaging will be used throughout treatment delivery to monitor the target location and control the radiation beam as necessary.

The trial’s primary outcome measure is grade 3 or higher gastrointestinal toxicity in the first 90 days after treatment, with secondary measures including overall survival at two years, distant progression-free survival at six months, and changes in patient-reported quality of life.

"Early evidence on the use of MRIdian to treat locally advanced pancreatic cancer suggests the potential for significantly prolonged survival and lower toxicity rates. Through this rigorously designed study, we hope to further validate the long-term benefits of treatment on the MRIdian," said Scott Drake, President and Chief Executive Officer of ViewRay. "We believe MRIdian’s unique combination of real-time visualization, automated beam control, and daily on-table treatment adaptation has the potential to become the standard of care in radiation oncology."

Along with Parag Parikh, M.D. from Henry Ford Cancer Institute, the trial is led by Percy Lee, M.D. from the University of California Los Angeles.

For more information on the SMART trial, please visit View Source

About the SMART Trial

The SMART trial is designed to enroll 133 participants with borderline resectable or inoperable locally advanced pancreatic cancer. Patients must be 18 years and older and have documented non-metastatic disease after 3 months of systemic therapy. Radiation therapy will be delivered using ViewRay’s MRIdian at a prescribed dose of 50 Gray (Gy) in 5 fractions. Each participant will be aligned in the treatment system with MRI image-guidance. On-table adaptive re-planning will be used when clinically indicated. In all patients, real-time MRI imaging will be used throughout treatment delivery to monitor the target location and control the radiation beam as necessary. The primary outcome measure of the study is grade 3 or higher gastrointestinal toxicity in the first 90 days after treatment. Secondary measures include overall survival at two years, distant progression-free survival at six months and changes in patient reported quality of life (pre-treatment to 12 months post-treatment and for longer periods up to five years).

On January 4, 2019 ADC Therapeutics, an oncology drug discovery and development company that specializes in the development of proprietary antibody drug conjugates (ADCs), reported that the first patient has been dosed in its Phase Ib clinical trial evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of ADCT-301 (camidanlumab tesirine) in patients with selected solid tumors that are locally advanced or metastatic (Press release, ADC Therapeutics, JAN 4, 2019, View Source [SID1234596069]).

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ADCT-301 is already being evaluated in relapsed and refractory Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). At the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, ADC Therapeutics presented interim data on 113 patients dosed in its Phase Ia/Ib clinical trial in lymphoma. In HL patients with a median of five prior lines of therapy and no other approved therapy options, the overall response rate was 86.5 percent, including a 43 percent complete response rate, at the dose being considered for a pivotal Phase II clinical trial that the Company anticipates initiating in 2019.

Jay Feingold, MD, PhD, Chief Medical Officer and Senior Vice President of Clinical Development at ADC Therapeutics, said, "We continue to be very encouraged by the anti-tumor activity of ADCT-301 in Hodgkin lymphoma and non-Hodgkin lymphoma. In addition, based on the immune-oncology potential ADCT-301 has demonstrated in preclinical studies, we are excited to be starting this clinical trial for ADCT-301 in solid tumors to see if we can make an impact and improve patient outcomes in multiple difficult-to-treat solid tumor cancers."

ADCT-301 in Solid Tumors

At the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 33rd Annual Meeting, ADC Therapeutics presented preclinical data showing that an engineered version of ADCT-301 demonstrated highly potent anti-tumor activity, both as a monotherapy and in combination with a checkpoint inhibitor, in multiple solid tumor models with infiltrating CD25-positive regulatory T cells (Tregs).

Patrick van Berkel, PhD, Senior Vice President of Research and Development at ADC Therapeutics, said, "ADCT-301 targets CD25, which is expressed on Tregs that infiltrate the local tumor environment. In preclinical models, a single dose of the CD25-targeted ADC induced strong and durable anti-tumor activity against established CD25-negative solid tumors with infiltrating Tregs both as a monotherapy and in combination with a checkpoint inhibitor. Moreover, re-challenged mice did not develop new tumors indicating the CD25-targeted ADC was able to induce tumor-specific protective immunity."

The Phase Ib trial of ADCT-301 in patients with advanced solid tumors has both dose escalation and cohort expansion parts. The dose escalation part is designed to establish a safe and tolerated dose and dosing schedule of ADCT-301 in these patients. The identified dose and dosing schedule will be studied in the dose expansion part. Approximately 50 patients will be enrolled in the trial.

For more information about this Phase Ib clinical trial in solid tumors, please visit www.clinicaltrials.gov (identifier NCT03621982).

About ADCT-301

ADCT-301 (camidanlumab tesirine) is an antibody drug conjugate (ADC) composed of a monoclonal antibody that binds to CD25 (HuMax-TAC, licensed from Genmab A/S), conjugated to a pyrrolobenzodiazepine (PBD) dimer toxin. Once bound to a CD25-expresing cell, ADCT-301 is internalized into the cell where enzymes release the PBD-based warhead. The intra-tumor release of its PBD warhead may cause bystander killing of neighboring tumor cells. In addition, the PBD warhead will trigger immunogenic cell death, which in turn will strengthen the immune response against tumor cells. In addition to the Phase Ib clinical trial in solid tumors, ADCT-301 is being evaluated in ongoing Phase Ia/Ib clinical trials in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma (NCT02432235).