On Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, reported new data showing that DecisionDx-SCC can independently risk-stratify patients with cutaneous squamous cell carcinoma (SCC) and one or more risk factors according to their biologic risk of metastasis, consistent with findings in previous development and validation studies.1,2 The poster was presented at the 2022 American College of Mohs Surgery (ACMS) Annual Meeting (Press release, Castle Biosciences, MAY 19, 2022, View Source [SID1234614876]).

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DecisionDx-SCC is Castle’s prognostic 40-gene expression profile (GEP) test designed to use a patient’s tumor biology to predict individual risk of metastasis for patients diagnosed with SCC who have one or more high-risk factors. The test stratifies patients into one of three classes based on their biologic risk of metastasis: Class 1 (low risk), Class 2A (moderate risk) or Class 2B (high risk).

"Identifying which patients are at an increased risk of disease progression and metastasis is a challenge for clinicians who may see hundreds of cutaneous squamous cell carcinoma cases in their practices each year," said study author Sarah T. Arron, M.D., Ph.D., Mohs surgeon and dermatologist at Peninsula Dermatology in Burlingame, California. "Using DecisionDx-SCC to add a patient’s biologic risk to our existing clinical and pathologic risk-assessment methods can improve our decision-making and help us to personalize treatment for our patients."

The poster, titled "Performance of the prognostic 40-gene expression profile (40-GEP) test for high-risk cutaneous squamous cell carcinoma (cSCC) in a second independent cohort," highlights data from a second, independent, multi-center study of high-risk SCC patients, consisting of 598 novel patient samples from 43 contributing centers. The poster can be viewed here. With the cohort of patients in this study, combined with the cohort of patients from the first validation study (n=420), the ability of DecisionDx-SCC to independently stratify risk has been confirmed in a total of 1,018 patients.

Kaplan-Meier analysis showed a statistically significant difference in metastasis-free survival (MFS) rates between DecisionDx-SCC Class 1, Class 2A and Class 2B results (p<0.0001, log-rank), demonstrating the ability of the test to risk-stratify patients according to their biologic metastatic risk. As demonstrated by univariate Cox regression analysis, DecisionDx-SCC Class 2A, Class 2B, traditional high-risk clinicopathologic risk factors, American Joint Committee on Cancer Eighth Edition (AJCC8) T3/T4 stages and Brigham and Women’s Hospital (BWH) T2b/T3 stages were all statistically associated with metastatic risk. A DecisionDx-SCC Class 2B result had the highest hazard ratio, 10.71, which was the strongest predictor of metastasis among the analyses. Further, multivariate Cox regression analysis demonstrated that DecisionDx-SCC independently and significantly contributed to risk stratification of patients when combined with traditional high-risk clinicopathologic factors (p<0.05 for Class 2A and 2B), BWH (p<0.001 for Class 2A and p<0.002 for Class 2B) or AJCC8 (p<0.001 for Class 2A and 2B) staging. This reinforces that the test’s results provide risk-stratification value on their own and can add clinical value when used as a complement to other risk-prediction systems.

Overall, the study data confirm what previous development and validation studies1,2 have substantiated: DecisionDx-SCC can accurately classify risk for metastasis in SCC patients with one or more risk factors and provides significant prognostic information independent from current risk prediction methods. Additionally, the study data further support the use of DecisionDx-SCC test results in combination with other risk-assessment and staging systems to guide more refined and risk-aligned patient care.

About DecisionDx-SCC

DecisionDx-SCC is a 40-gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous squamous cell carcinoma metastasis for patients with one or more risk factors. The test result, in which patients are stratified into a Class 1 (low), 2A (moderate) or 2B (high) risk category, predicts individual metastatic risk to inform risk-appropriate management.

Peer-reviewed publications have demonstrated that DecisionDx-SCC is an independent predictor of metastatic risk and that integrating DecisionDx-SCC with current prognostic methods can add positive predictive value to clinician decisions regarding staging and management.

More information about the test and disease can be found at www.CastleTestInfo.com.

On Mirati 19, 2022 Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, reported that it has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for adagrasib for the treatment of patients with non-small cell lung cancer (NSCLC) harboring the KRASG12C mutation who have received at least one prior systemic therapy (Press release, Mirati, MAY 19, 2022, View Source [SID1234614892]).

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The MAA is supported by data from the registration enabling cohort of the Phase 2 KRYSTAL-1 study evaluating adagrasib 600mg BID in patients with advanced NSCLC harboring the KRASG12C mutation following prior treatment with immunotherapy and chemotherapy, either together or sequentially. The Company reported positive topline data from this cohort in September 2021 and plans to present detailed results at the upcoming 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

"The submission of our application to the EMA is a significant milestone for Mirati and brings us closer to expanding the potential availability of adagrasib to patients with KRASG12C-mutated lung cancer in the European Union, if approved," said Charles Baum, M.D., Ph.D., president, founder and head of research and development, Mirati Therapeutics, Inc. "Therapeutic options for KRASG12C-mutated lung cancer are limited, and this submission is an important step forward in our goal to deliver innovative, differentiated therapies in areas of high unmet need. We look forward to working with the EMA to potentially bring this therapy to patients. We also thank the patients and investigators who make our work possible by participating in clinical trials."

The adagrasib New Drug Application (NDA) is currently being reviewed by the U.S. Food and Drug Administration (FDA) for Accelerated Approval (Subpart H) as a treatment for patients with NSCLC harboring the KRASG12C mutation who have received at least one prior systemic therapy. The application is being reviewed under the FDA Real Time Oncology Review (RTOR) pilot program, which aims to explore a more efficient review process that ensures safe and effective treatments are made available to patients as early as possible. Adagrasib has also achieved Breakthrough Therapy Designation in the U.S. as a potential treatment for patients with NSCLC harboring the KRASG12C mutation who have received at least one prior systemic therapy.

About Adagrasib (MRTX849)
Adagrasib is an investigational, highly selective, and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C-mutated cancers, as the KRASG12C protein regenerates every 24–48 hours. Adagrasib is being evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including non-small cell lung cancer (NSCLC), colorectal cancer and pancreatic cancer. For more information visit Mirati.com/science.

Mirati has an Expanded Access Program (EAP) for investigational adagrasib for the treatment of eligible patients with KRASG12C-mutated cancers, regardless of tumor type, in the U.S. Learn more about the EAP at Mirati.com/expanded-access-policy.

On May 19, 2022 The European Organisation for Research and Treatment of Cancer (EORTC) reported its continued partnership with Alliance Healthcare, one of the largest pharmaceutical wholesalers in Europe (Press release, EORTC, MAY 19, 2022, View Source [SID1234614861]). Specifically, the collaboration supports the organisation’s SPECTA platform, a pan-European translational research infrastructure for all tumour types including rare cancers.

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The EORTC SPECTA platform allows for the rapid implementation of new clinical trials and robust translational cancer research aimed at increasing our understanding of cancers in order to guide a more targeted clinical research and treat patients effectively.

Alliance Healthcare was previously owned by Walgreens Boots Alliance (WBA) until June 2021. Since then, Alliance Healthcare is a wholly owned subsidiary of AmerisourceBergen and the EORTC is delighted that its support and commitment to SPECTA is to continue under this new ownership. The fantastic support that Alliance Healthcare as part of WBA has provided over the past 10 years (since 2011) will persist to further reinforce and strengthen recognition of the SPECTA platform as the leading pan-European translational research infrastructure. The partnership with Alliance Healthcare under the umbrella of AmerisourceBergen will ensure the continuation of SPECTA’s work in personalised cancer medicine, helping guide patients’ treatments, but also advance our understanding of cancer biology to help treat more patients effectively.

Through the growth of SPECTA’s translational clinical research, it provides hope to thousands of patients. One patient with papillary thyroid cancer said that their "current treatment was defined after [their] inclusion in SPECTA" and after previous treatments didn’t work.

Treating oncologists also benefit from SPECTA. Pr. Jean-Yves Blay has said "the SPECTA study enables [the opportunity] to gain more understanding on the nature of the disease and to guide the treatment of many patients with rare cancer, which is quite unique."

Today, SPECTA’s ever-growing cancer clinical research platform includes 128 authorized research doctors in 17 countries. More than 1330 patients have participated in 3 clinical research projects with over 1200 individual result reports provided to patients and providing guidance for their treatment.

EORTC CEO, Dr Denis Lacombe commented "EORTC looks forward to continue working with Alliance Healthcare and AmerisourceBergen, pushing the boundaries of understanding cancer and furthering the standard of care for cancer patients in the European continent, through SPECTA."

Juan Guerra, SVP Managing Director at Alliance Healthcare said "I am extremely proud of the efforts of Alliance Healthcare colleagues Europe-wide over the last decade. The work the EORTC does, and advancements in cancer therapies and treatment SPECTA brings about, is critical in the fight against this disease. I am extremely happy that under our new AmerisourceBergen ownership we are continuing to help and support through a range of fund-raising initiatives and a donation from the AmerisourceBergen Foundation as together we aim to improve the health and wellbeing of patient populations."

On May 19, 2022 Alchemab Therapeutics, a biotechnology company focused on the discovery and development of naturally-occurring protective antibodies and immune repertoire-based patient stratification tools, reported the publication of research demonstrating the potential of AntiBERTa (Antibody-specific Bi-directional Encoder Representation and Transformers), a transformer neural network that reads the components of an antibody amino acid sequence, to deeply understand the structure and function of antibody sequences (Press release, Alchemab Therapeutics, MAY 19, 2022, View Source [SID1234614877]). The article, titled "Deciphering the language of antibodies using self-supervised learning" has been published online in the journal Patterns. AntiBERTa is a 12-layer transformer model that provides a contextualized numeric representation of antibody sequences and learns biologically relevant information.

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"AntiBERTa forms the basis of Alchemab’s machine learning platform, providing a pre-trained model which is primed for multiple downstream tasks relevant to antibody drug discovery," said Jake Galson, Ph.D., Head of Technology at Alchemab. "We have already demonstrated the utility of AntiBERTa for binding-site prediction, and this is helping us to better identify convergent antibodies associated with disease resilience. We are excited to further progress our research and leverage our expertise to develop pioneering ways of treating diseases in the field of immunotherapy."

The study found that the B cell receptor (BCR) sequence representations separate according to mutational load and the underlying BCR V gene segments used. Importantly, there is distinct partitioning of BCRs derived from naïve versus memory B cells, suggesting that functionally important information is captured by the model. Finally, the model recognized pairs of positions within the BCR sequence that form contacts in three-dimensional space. These data demonstrate that AntiBERTa learns various characteristics of the BCRs, such as B cell origin, activation level, immunogenicity, and structure.

Dr. Jane Osbourn, PhD, Co-founder and Chief Scientific Officer of Alchemab, commented: "Our AntiBERTa technology has the potential to transform our ability to understand antibody structure and function and will inform our understanding of antibody paratopes, or the amino acid sequences comprising the site at which antibodies bind to antigens. It will also enable Alchemab to continue to build its unbiased platform to identify novel oncology and neurodegenerative targets. Alchemab’s novel approach learns from nature and naturally optimized antibodies and works backwards to uncover the most important targets and pathways involved in disease modulation. This approach has been very successful, leading to the identification of several novel oncology and neurodegenerative disease drug targets."

On May 19, 2022 Inhibrx, Inc. (Nasdaq: INBX), a biotechnology company with four clinical programs in development and an emerging pre-clinical pipeline, reported that it will be presenting details on the trial design for the INBRX-109 Phase 2 potentially registration-enabling trial in conventional chondrosarcoma at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") Annual Meeting to be held June 3rd through June 7th, 2022 in Chicago, Illinois (Press release, Inhibrx, MAY 19, 2022, View Source [SID1234614894]).

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Details on the poster presentation are shared below:

Title: A randomized, placebo-controlled phase 2 trial of INBRX-109 in unresectable or metastatic conventional chondrosarcoma
Track/Session: Sarcoma
Poster number:486a
Presenter: Sant P. Chawla, MD
Date & Time: Sunday, June 5, 2022 from 9 a.m. to 11 a.m. CST
Location: Exhibit Hall A

The poster will be available on-demand on the ASCO (Free ASCO Whitepaper) website for attendees beginning at 9:00 AM CST on Friday, June 3, 2022. Upon release at ASCO (Free ASCO Whitepaper), the scientific poster will be accessible through Inhibrx’s website at View Source

About Chondrosarcoma

Chondrosarcoma is an orphan bone cancer with approximately 2,800 new patients diagnosed annually in the United States and the European Union. There are currently no systemic therapies approved for the treatment of chondrosarcoma.

About INBRX-109

INBRX-109 is a precision-engineered, tetravalent death receptor 5 (DR5) agonist antibody designed to exploit the tumor-biased cell death induced by DR5 signaling.

In January 2021, the FDA granted Fast Track designation to INBRX-109 for the treatment of patients with unresectable or metastatic conventional chondrosarcoma. Further, in December 2021, FDA granted Orphan Drug Designation to INBRX-109 for this indication.

In November 2021, Inhibrx provided updated results from its ongoing Phase 1 clinical trial evaluating the efficacy and safety of INBRX-109 in patients with conventional chondrosarcoma. Preliminary disease control was observed in 16 of the 18 evaluable patients (89%) measured by RECISTv1.1, with two of the 18 achieving partial responses (11%). Based on preliminary results of the ongoing Phase 1 trial, the median progression-free survival (PFS) is 7.4 months, and the median overall survival has not been reached. Three patients have exceeded 61 weeks on treatment with INBRX-109, with 77 weeks being the longest duration of stable disease observed to date.

In June 2021, Inhibrx initiated a randomized, blinded, placebo-controlled, potentially registration-enabling Phase 2 trial of INBRX-109 in conventional chondrosarcoma. The trial will be conducted at approximately 51 sites within eight countries, with 30 of those sites in the United States.