On May 5, 2020 Amgen (NASDAQ:AMGN) reported that the U.S. District Court in Delaware issued a decision upholding the validity of patent claims from three patents that protect Amgen’s multiple myeloma therapy KYPROLIS (carfilzomib) (Press release, Amgen, MAY 5, 2020, View Source [SID1234557057]). Today’s decision will prevent Cipla Limited, and Cipla USA, Inc. (collectively "Cipla") from making, using, selling, offering to sell, or importing its generic version of KYPROLIS until expiration of these three U.S. patents. The latest patent expiry is in December 2027.

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Onyx Therapeutics, Inc., an indirect, wholly-owned subsidiary of Amgen Inc., brought a patent infringement suit against Cipla in 2016. The decision comes after the Delaware court held a bench trial in May 2019. Prior to trial, Cipla acknowledged that its generic product would infringe all of the asserted claims, leaving only the issue of validity of the asserted patents to be addressed by the court.

KYPROLIS is approved for the treatment of patients with relapsed or refractory multiple myeloma who previously received one to three lines of other therapy. KYPROLIS is also indicated in combination with dexamethasone or with lenalidomide plus dexamethasone. Three patents that are the subject of the decision are: U.S. Patent No. 7,417,042, U.S. Patent No. 7,737,112 and U.S. Patent No. 8,207,125.

About KYPROLIS

INDICATIONS

KYPROLIS (carfilzomib) is indicated in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.

KYPROLIS is indicated as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.

IMPORTANT SAFETY INFORMATION FOR KYPROLIS

Cardiac Toxicities

New onset or worsening of pre-existing cardiac failure (e.g., congestive heart failure, pulmonary edema, decreased ejection fraction), restrictive cardiomyopathy, myocardial ischemia, and myocardial infarction including fatalities have occurred following administration of KYPROLIS. Some events occurred in patients with normal baseline ventricular function. Death due to cardiac arrest has occurred within one day of administration.

Monitor patients for signs or symptoms of cardiac failure or ischemia. Evaluate promptly if cardiac toxicity is suspected. Withhold KYPROLIS for Grade 3 or 4 cardiac adverse events until recovery, and consider whether to restart at 1 dose level reduction based on a benefit/risk assessment.

While adequate hydration is required prior to each dose in Cycle 1, monitor all patients for evidence of volume overload, especially patients at risk for cardiac failure. Adjust total fluid intake as clinically appropriate.

For patients ≥ 75 years, the risk of cardiac failure is increased. Patients with New York Heart Association Class III and IV heart failure, recent myocardial infarction, conduction abnormalities, angina, or arrhythmias may be at greater risk for cardiac complications and should have a comprehensive medical assessment prior to starting treatment with KYPROLIS and remain under close follow-up with fluid management.

Acute Renal Failure

Cases of acute renal failure, including some fatal renal failure events, and renal insufficiency adverse events (including renal failure) have occurred. Acute renal failure was reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received KYPROLIS monotherapy. Monitor renal function with regular measurement of the serum creatinine and/or estimated creatinine clearance. Reduce or withhold dose as appropriate.

Tumor Lysis Syndrome

Cases of Tumor Lysis Syndrome (TLS), including fatal outcomes, have occurred. Patients with a high tumor burden should be considered at greater risk for TLS. Adequate hydration is required prior to each dose in Cycle 1, and in subsequent cycles as needed. Consider uric acid lowering drugs in patients at risk for TLS. Monitor for evidence of TLS during treatment and manage promptly, and withhold until resolved.

Pulmonary Toxicity

Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, and acute diffuse infiltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred. Some events have been fatal. In the event of drug-induced pulmonary toxicity, discontinue KYPROLIS.

Pulmonary Hypertension

Pulmonary arterial hypertension (PAH) was reported. Evaluate with cardiac imaging and/or other tests as indicated. Withhold KYPROLIS for PAH until resolved or returned to baseline and consider whether to restart based on a benefit/risk assessment.

Dyspnea

Dyspnea was reported in patients treated with KYPROLIS. Evaluate dyspnea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes. Stop KYPROLIS for Grade 3 or 4 dyspnea until resolved or returned to baseline. Consider whether to restart based on a benefit/risk assessment.

Hypertension

Hypertension, including hypertensive crisis and hypertensive emergency, has been observed, some fatal. Control hypertension prior to starting KYPROLIS. Monitor blood pressure regularly in all patients. If hypertension cannot be adequately controlled, withhold KYPROLIS and evaluate. Consider whether to restart based on a benefit/risk assessment.

Venous Thrombosis

Venous thromboembolic events (including deep venous thrombosis and pulmonary embolism) have been observed. Thromboprophylaxis is recommended for patients being treated with the combination of KYPROLIS with dexamethasone or with lenalidomide plus dexamethasone. The thromboprophylaxis regimen should be based on an assessment of the patient’s underlying risks.

Patients using hormonal contraception associated with a risk of thrombosis should consider an alternative method of effective contraception during treatment.

Infusion Reactions

Infusion reactions, including life-threatening reactions, have occurred. Signs and symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, laryngeal edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina. These reactions can occur immediately following or up to 24 hours after administration. Premedicate with dexamethasone to reduce the incidence and severity of infusion reactions. Inform patients of the risk and of symptoms and seek immediate medical attention if they occur.

Hemorrhage

Fatal or serious cases of hemorrhage have been reported. Hemorrhagic events have included gastrointestinal, pulmonary, and intracranial hemorrhage and epistaxis. Promptly evaluate signs and symptoms of blood loss. Reduce or withhold dose as appropriate.

Thrombocytopenia

KYPROLIS causes thrombocytopenia with recovery to baseline platelet count usually by the start of the next cycle. Monitor platelet counts frequently during treatment. Reduce or withhold dose as appropriate.

Hepatic Toxicity and Hepatic Failure

Cases of hepatic failure, including fatal cases, have occurred. KYPROLIS can cause increased serum transaminases. Monitor liver enzymes regularly regardless of baseline values. Reduce or withhold dose as appropriate.

Thrombotic Microangiopathy

Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), including fatal outcome, have occurred. Monitor for signs and symptoms of TTP/HUS. Discontinue if diagnosis is suspected. If the diagnosis of TTP/HUS is excluded, KYPROLIS may be restarted. The safety of reinitiating KYPROLIS is not known.

Posterior Reversible Encephalopathy Syndrome (PRES)

Cases of PRES have occurred in patients receiving KYPROLIS. If PRES is suspected, discontinue and evaluate with appropriate imaging. The safety of reinitiating KYPROLIS is not known.

Increased Fatal and Serious Toxicities in Combination with Melphalan and Prednisone in Newly Diagnosed Transplant-ineligible Patients

In a clinical trial of transplant-ineligible patients with newly diagnosed multiple myeloma comparing KYPROLIS, melphalan, and prednisone (KMP) vs bortezomib, melphalan, and prednisone (VMP), a higher incidence of serious and fatal adverse events was observed in patients in the KMP arm. KMP is not indicated for transplant-ineligible patients with newly diagnosed multiple myeloma.

Embryo-fetal Toxicity

KYPROLIS can cause fetal harm when administered to a pregnant woman.

Females of reproductive potential should be advised to avoid becoming pregnant while being treated with KYPROLIS and for 6 months following the final dose. Males of reproductive potential should be advised to avoid fathering a child while being treated with KYPROLIS and for 3 months following the final dose. If this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Adverse Reactions

The most common adverse reactions in the combination therapy trials: anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia, pyrexia, insomnia, muscle spasm, cough, upper respiratory tract infection, hypokalemia.

The most common adverse reactions in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache, cough, edema peripheral.

On May 5, 2020 Scholar Rock (NASDAQ: SRRK), a clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, reported the initiation of patient dosing in the DRAGON Phase 1 dose escalation and dose expansion clinical trial of SRK-181 in patients with locally advanced or metastatic solid tumors (Press release, Scholar Rock, MAY 5, 2020, businesswire.com/news/home/20200505005992/en/Scholar-Rock-Announces-Initiation-Patient-Dosing-Phase [SID1234557056]). SRK-181 is a potent and highly selective inhibitor of latent TGFβ1 activation and is being developed to increase responses to immunotherapy by overcoming primary resistance to anti-PD-1 or anti-PD-L1 antibody therapy.

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"Based on emerging evidence in the field from human and preclinical data implicating TGFβ1 as a key culprit in primary resistance to anti-PD-(L)1 therapy, we are excited to be investigating a rational approach to combination immunotherapy," said Yung Chyung, M.D., Chief Medical Officer of Scholar Rock. "Our team’s focus and determination to advance SRK-181 and this Phase 1 trial, particularly as the evolving COVID-19 pandemic has resulted in various challenges, has been truly impressive. We remain committed to our mission of developing important therapies for patients and the initiation of dosing in this proof-of-concept trial represents an important milestone for us and our TGFβ1 platform."

DRAGON Phase 1 Proof-of-Concept Trial

The DRAGON Phase 1 open-label, dose escalation and dose expansion clinical trial is evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of SRK-181 in adult patients with locally advanced or metastatic solid tumors enrolled across multiple sites in the U.S. The two-part trial consists of a dose escalation portion (Part A) for SRK-181 as both a single agent and in combination with approved anti-PD-(L)1 therapy, followed by a dose expansion portion (Part B) evaluating SRK-181 in combination with approved anti-PD-(L)1 therapy in multiple tumor-specific cohorts. Intravenous (IV) SRK-181 is administered every 3 weeks (Q3W) and additional dosing regimens may be explored.

Due to the COVID-19 pandemic and the anticipated pace of enrollment, Scholar Rock now plans to provide an update on dose escalation of SRK-181 as a single agent as well as in combination with anti-PD-(L)1 therapy in the fourth quarter of 2020. Clinical response and safety data are anticipated in 2021. Timing of data read-outs may be further impacted by COVID-19-related disruptions.

Part A Dose Escalation: Part A of the Phase 1 trial assesses SRK-181 both as a single agent and in combination with approved anti-PD-(L)1 therapy and will be conducted in a staggered fashion. The safety, PK, and activity of SRK-181 will be evaluated, including effects upon biomarkers, such as CD8 T cell infiltration, based on biopsies before and after treatment.

Part A1 evaluates SRK-181 as a single agent in patients with locally advanced or metastatic solid tumors. The dose escalation will follow a modified 3+3 design and assess doses starting at 80 mg up to 2400 mg (based on an average body weight of approximately 80 kg).

Part A2 evaluates SRK-181 in combination with anti-PD-(L)1 therapy in patients with locally advanced or metastatic solid tumors that exhibit primary resistance to anti-PD-(L)1 antibodies. Lack of response is characterized as either stable disease or progressive disease following at least three cycles of treatment with an approved anti-PD(L)1 therapy, either alone or in combination with chemotherapy. Patients must have received their most recent dose of anti-PD-(L)1 therapy within six months of enrollment. In combination with SRK-181, patients will be treated with the same anti-PD-(L)1 therapy that they had previously tried and did not experience a response. The dose escalation will follow a 3+3 design and assess doses up to 2400 mg.

Part B Dose Expansion: Part B of the trial consists of multiple parallel cohorts to evaluate the anti-tumor activity of SRK-181 in combination with anti-PD-(L)1 therapy. The target indications are expected to include non-small cell lung cancer, urothelial carcinoma, and cutaneous melanoma, amongst other solid tumor types.

Each cohort will enroll up to 40 patients with locally advanced or metastatic solid tumors for which anti-PD-(L)1 therapy is approved and have demonstrated primary resistance, characterized as a lack of response (stable or progressive disease) following at least three cycles of treatment. Patients must have received their most recent dose of anti-PD-(L)1 therapy within six months of enrollment. Similar to Part A2, patients will be treated with SRK-181 in combination with the same anti-PD-(L)1 therapy that they had previously tried and did not experience a response.

About SRK-181

SRK-181 is a potent and highly selective inhibitor of TGFβ1 activation and is an investigational product candidate being developed to overcome primary resistance to checkpoint inhibitor therapy, such as anti-PD-(L)1 antibodies. TGFβ1 is the predominant TGFβ isoform expressed in many human tumors, particularly for those tumors where checkpoint therapies are currently approved. Based on analyses of human tumors that are resistant to anti-PD-(L)1 therapy, data suggests TGFβ1 is a key contributor to excluding immune cell entry into the tumor microenvironment, thereby preventing normal immune function. By overcoming this immune cell exclusion, Scholar Rock believes SRK-181 has the potential to induce tumor regression when administered in combination with anti-PD-(L)1 therapy. A Phase 1 proof-of-concept clinical trial in patients with locally advanced or metastatic solid tumors is ongoing. The effectiveness and safety of SRK-181 have not been established and SRK-181 has not been approved for any use by the FDA or any other regulatory agency.

On May 5, 2020 PierianDx, the leading clinical genomics informatics company, and University Hospital of Augsburg reported a strategic development partnership to optimize an interpretation and reporting workflow based on the PierianDx Clinical Genomics Workspace platform for the AmpliSeq for Illumina Myeloid and Focus assays (Press release, PierianDx, MAY 5, 2020, View Source [SID1234557055]). Under the agreement, University Hospital of Augsburg will use the PierianDx Clinical Genomics Workspace to create an out-of-the-box bioinformatics and clinical genomics reporting workflow optimized for these AmpliSeq assays and tailored to the specific needs of the European market.

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The AmpliSeq Myeloid and Focus assays accommodate DNA or RNA samples and investigate a number of genes, gene fusions, or expression levels with known relevance to solid- and blood-based cancers. These assays, already in use by University Hospital of Augsburg, are a key part of the hospital’s overall plan to expand its NGS testing program to offer precision medicine treatments to the community it serves.

As assays become more sophisticated, interpretation and reporting have usurped library preparation and sequencing as the most complex portion of the workflow. Manually interpreting each case is simply not scalable, especially with frequently changing literature, guidelines, and clinical trials.

To address these challenges, University Hospital of Augsburg will use the PierianDx Clinical Genomics Workspace, which includes a highly curated, rules-based knowledgebase and clinical sharing network for the rapid classification of variants. Concurrent to its use of Clinical Genomics Workspace, University Hospital of Augsburg will work with PierianDx on an ongoing basis to refine a European market-specific reporting workflow for the AmpliSeq assays. The result will be a refined clinical genomics report, complete with assay-specific variant filters, that is optimized with European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) guidelines, EMA drug labels, and active and recruiting European clinical trials, all of which have been included in the PierianDx platform since 2019.

Sebastian Dintner, Head of Molecular Pathology, University Hospital of Augsburg, states: "We are happy to work with PierianDx to optimize the workflow and pioneer one of the first region-specific reporting solutions for the AmpliSeq assays. By doing so, we will be able to accomplish our mission of expanding our precision medicine offerings to provide advanced cancer care for our patients."

"As we provide streamlined interpretation and supporting solutions for leading assay manufacturers, it’s imperative that we acknowledge region-specific needs of the market," states Rakesh Nagarajan, Founder, President, and Chief Technology and Visionary Officer of PierianDx. "We are excited to partner with University Hospital of Augsburg because it helps us refine our system for the European market."

On May 5, 2020 Bayer reported the launch of Test4TRK program in collaboration with NeoGenomics, Inc. to offer genomic cancer testing for NTRK gene fusions at no cost for patients with RAI-refractory (RAI-R) differentiated thyroid carcinoma (DTC) and metastatic colorectal cancer (mCRC) with high microsatellite instability (MSI-H) (Press release, Bayer, MAY 5, 2020, View Source [SID1234557054]). NTRK gene fusions, which have been shown to drive tumor growth, are more commonly found in patients with MSI-H mCRC and RAI-R DTC and may play a role in disease management.1-3 Bayer will cover the full cost of the test regardless of the results, treatment decision and patient’s insurance coverage. All eligible patients who enroll and opt-in to the program will receive an RNA-based next-generation sequencing (NGS) test, NTRK NGS Fusion Profile. Patients with an adequate tissue sample will also receive a Pan-Tropomyosin receptor kinase (Pan-TRK) Immunohistochemistry (IHC) test.

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Healthcare professionals and patients can visit www.Test4TRK.com to learn more and download the test request form or call Bayer Medical Communications at +1-888-84BAYER (+1-888-842-2937) for questions on NTRK gene fusions and TRK fusion cancer.

"The results of a genomic cancer test may be a deciding factor in treatment selection, especially for patients with differentiated thyroid cancer who have limited options," said Marcia S. Brose, M.D., Ph.D., Director of the Center for Rare Cancers and Personalized Therapy at the Abramson Cancer Center of the University of Pennsylvania and an Associate Professor in Otorhinolaryngology: Head and Neck Surgery at Penn’s Perelman School of Medicine, who collaborated on the development of the testing platform. "If we implement comprehensive genomic testing early upon diagnosis to uncover NTRK gene fusions, we may have a deeper understanding of patients’ tumors in aiding treatment decisions."

Genomic cancer testing helps detect changes in a tumor’s DNA, called genomic alterations, that can determine how the cancer behaves and why it grows or spreads.4 30-49 percent of patients who undergo genomic cancer testing may have actionable genomic alterations, meaning the alterations can be matched to treatments that have been approved or are in clinical trials.5,6

"After receiving a cancer diagnosis, patients and their loved ones critically need information that can help guide the course of their treatment journey," said Anjee Davis, president of Fight Colorectal Cancer (Fight CRC). "The Test4TRK program aligns with our commitment to empowering patients with educational resources. Colorectal cancer patients need to be armed with biomarker testing because their biomarkers can have an impact on treatment decisions, especially MSI-H. This can inform treatment plans and reduce financial barriers that could prevent some patients from receiving personalized care."

Bayer has developed this program in collaboration with patient organizations Thyroid Cancer Survivors’ Association, Inc. (ThyCa) and Fight CRC as well as Marcia S. Brose, MD, PhD of the University of Pennsylvania. Dr. Brose serves in an advisory role for Bayer and receives honoraria and funding for research support.

The Test4TRK program provides testing for an NTRK gene fusion, which occurs when an NTRK gene joins together, or fuses, with a different, unrelated gene. The NTRK gene fusion creates certain proteins (TRK fusion proteins) that can cause cancer cells to multiply and form a tumor.1 Cancers with NTRK gene fusions can occur in tumors that originate in different sites in the body in varying frequencies and are called TRK fusion cancers.7

"It is critical cancer patients have access to genomic testing for NTRK gene fusions to inform treatment decisions," said Joseph Germino, M.D., Vice President of Medical Affairs, Oncology at Bayer. "Bayer is providing the Test4TRK program as part of our continued efforts to empower the community and help increase the accuracy of cancer diagnoses to improve patient outcomes."

About the Test4TRK Program
Test4TRK is a Bayer-sponsored program offering laboratory testing for NTRK gene fusions (histology and molecular subject to tissue availability) at no cost to eligible patients with RAI-refractory (RAI-R) differentiated thyroid carcinoma (DTC) and metastatic colorectal cancer (mCRC) with high microsatellite instability (MSI-H). The test results provide information on whether the tumor harbors an NTRK gene fusion to aid in the treatment decision. Bayer will cover the full cost of the test regardless of the test results, treatment decision and patient’s insurance coverage for up to 500 patients in the U.S. Bayer will not cover the associated costs of extracting a viable tumor specimen. For more information, visit www.Test4TRK.com.

About Genomic Cancer Testing
It is important for patients diagnosed with cancer to discuss genomic cancer testing with their healthcare provider (HCP). Genomic cancer testing can identify DNA alterations, or changes, within cancer cells that determine how a tumor behaves or why it grows.4 Genomic cancer testing may help HCPs match patients to approved or investigational therapies based on the specific alteration identified.

About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer now expands to six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.

On May 5, 2020 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported the publication of a clinical utility model for its cutaneous squamous cell carcinoma (SCC) prognostic test, DecisionDx-SCC, for patients diagnosed with high-risk cutaneous SCC (Press release, Castle Biosciences, MAY 5, 2020, View Source [SID1234557053]). The test is expected to launch commercially in the second half of 2020.

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The article titled, "Integrating gene expression profiling into NCCN high-risk cutaneous squamous cell carcinoma management recommendations: impact on patient management," was published in the peer-reviewed journal, Current Medical Research and Opinion (CMRO).

This publication proposes a framework for integration of DecisionDx-SCC into existing management pathways for a risk-appropriate approach in high-risk cutaneous SCC patients (as defined by having one or more high-risk factors and consistent with the National Comprehensive Cancer Network (NCCN) guidelines).

"Castle’s DecisionDx-SCC test is designed to stratify risk of regional or distant metastasis in high-risk cutaneous SCC patients," said Aaron Farberg, M.D., first author, Icahn School of Medicine at Mount Sinai, New York and Arkansas Dermatology Skin Cancer Center, Little Rock, Arkansas. "This manuscript proposes a framework for clinical use of this test, along with current risk stratification tools within established management pathways. The expectation is that the test will enable more informed clinical decisions about adjuvant therapy and other management options."

Disease and Study Background

Approximately 1 million patients are diagnosed with SCC of the skin in the U.S. each year, and the incidence continues to grow; while the majority of patients have a favorable prognosis, approximately 200,000 patients are identified as high risk.
NCCN guidelines for SCC define treatment pathways based on risk of local recurrence or metastasis. For SCC, there are two clinicopathologically defined categories: low risk and high risk. NCCN defines high risk as SCC patients with one or more of several high-risk clinicopathologic features.
The study objective was to integrate gene expression profiling into the management of high-risk SCC within NCCN guidelines to improve risk-aligned management recommendations.
DecisionDx-SCC stratifies patients into three categories based on risk of metastasis: Class 1 (low-risk), Class 2A (high-risk) and Class 2B (highest-risk).This study was designed to evaluate possible changes in management for 300 NCCN high-risk cutaneous SCC patients, when considering DecisionDx-SCC test results.
Study Findings

Combining DecisionDx-SCC class with American Joint Committee on Cancer T stage identified a group of 159 low-risk patients (Class 1, T1-T2) with a 7.5% rate of metastasis. Similarly, combining test results with Brigham and Women’s Hospital staging identified 173 patients with a metastasis rate of 8.1%. Rates in both groups approached the metastasis rate of 6% observed for the general cutaneous SCC patient population.
By comparison, Class 2B patients in the study (n=24) had rates of metastasis equal to or surpassing 50%, regardless of the staging system with which the Class 2B result was combined, a rate that may warrant an NCCN-defined, high intensity management plan.
Following incorporation of DecisionDx-SCC results with T stage for 300 patients with NCCN high-risk features, more than 50% would have been recommended a low intensity management plan, while 34-39% would be recommended for a moderate intensity plan and only 8% for a high intensity plan.
The DecisionDx-SCC test is the second skin cancer test discovered, developed and validated by Castle Biosciences.

About Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (SCC) is one of the most common cancers. Approximately 1 million patients are diagnosed with SCC each year in the U.S. While the majority of patients have a favorable prognosis, approximately 200,000 patients are identified as high risk. National guidelines provide for broad, aggressive treatment plan recommendations relative to low-risk patients. Traditional clinicopathologic based risk-factor staging systems suffer from low positive predictive value; meaning many more patients are classified as high risk than actually develop metastatic disease. This may lead to over- and under-treatment of a substantial number of cutaneous SCC patients. To address this clinical need, Castle Biosciences has developed a gene expression profile test designed to improve upon current staging systems and identify patients with cutaneous SCC at high risk for metastasis, in order to enable more informed, objective clinical decisions regarding adjuvant therapy and other management options.