On December 3, 2024 Caris Life Sciences (Caris), a leading next-generation AI TechBio company and precision medicine pioneer, reported that the company and collaborators from leading cancer centers, including those within the Caris Precision Oncology Alliance (Caris POA), will collectively present seven studies across a range of breast cancer types, including male breast cancer, at the San Antonio Breast Cancer Symposium (SABCS) from December 10-13, 2024 (Booth #1217) (Press release, Caris Life Sciences, DEC 2, 2024, View Source [SID1234648773]). The research highlights the capability of Caris’ extensive multimodal database to uncover new cancer insights, which may significantly influence a patient’s diagnosis, prognosis, treatment plan and therapeutic response.

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"The research being presented at this year’s San Antonio Breast Cancer Symposium is a testament to Caris’ continued commitment to data-driven molecular innovation and the power of our ever-expanding network of collaborators to answer some of today’s pressing questions in precision oncology," said Caris EVP and Chief Medical Officer George W. Sledge, Jr., MD. "More than half of the studies presented focus on male breast cancer, an often-overlooked form of breast cancer. The findings underscore the critical role of comprehensive profiling in cancer care and the power of large clinico-genomic datasets to enable the identification of new biomarkers with clinical implications across diverse tumor types, including rare cancers."

The research highlights the capability of Caris’ extensive multimodal database to uncover new cancer insights

"Our comprehensive molecular profiling coupled with rich clinical data is enabling Caris to help clinicians make the best treatment choices, researchers to discover novel cancer biology, and the biopharmaceutical industry to develop the next breakthrough medicines," said Caris President David Spetzler, MS, PhD, MBA. "Our vast real-world evidence from over 748,000 cases, including over 550,000 with matched molecular data and outcomes, enables our team and research collaborators to better understand the biological hallmarks of cancers and how they impact clinical outcomes, paving the way for personalized therapies and improved patient outcomes."

Spotlight Poster Presentations include:

A Caris study titled "Molecular and Immune Landscape of Metaplastic Triple Negative Breast Cancer Compared with Invasive Ductal Triple Negative Breast Cancer" (Presentation #PS17-02) will be featured in Concurrent Poster Spotlight Session 17, named "Early Triple Negative Breast Cancer," on Thursday, December 12, from 5:30 – 6:30 p.m. CST in the Stars at Night Ballroom 1-2. The study was performed in collaboration with Caris Precision Oncology Alliance (Caris POA) members Dana-Farber Cancer Institute, Norris Comprehensive Cancer Center, Legorreta Cancer Center at Brown University and Yale School of Medicine, as well as the Mayo Clinic.
In the featured study, the molecular and immunological landscapes of metaplastic triple-negative breast cancer (M-TNBC) were investigated using Caris’ Next-Generation Sequencing (NGS) technology. The results indicate that M-TNBC is associated with an aggressive disease biology, with differential molecular and immune features compared to invasive ductal TNBC. A better understanding of these differences may help inform disease outcomes, provide a rationale for tailored therapeutic approaches and guide the design of future treatments for M-TNBC, a rare and aggressive form of breast cancer.

A Caris study titled "Mechanisms of Resistance to Trastuzumab Deruxtecan in Breast Cancer Elucidated by Multi-omic Molecular Profiling" (Presentation #PS13-09) will be featured during Concurrent Poster Spotlight Session 13, named "Molecular Determinants of Therapeutic Response and Resistance – Spotlight on CDK 4/6i and ADCs" on Friday, December 13 from 7:00 – 8:30 a.m. CST in the Stars at Night Ballroom 1-2. Caris EVP and Chief Medical Officer George W. Sledge Jr., MD will present results of the study conducted by Caris scientists.
In this study, whole transcriptome sequencing (WTS), immunohistochemistry and real-world clinical data were analyzed for more than 2,000 Trastuzumab Deruxtecan (T-DXd)-treated breast cancer samples. This multi-omic approach revealed a clinically relevant mechanism of resistance to T-DXd, a drug widely used in the treatment of metastatic HER-2 low and HER2-positive breast cancer. In T-DXd-treated patients, clinical outcome was a function of trastuzumab target expression and expression of ABCC1, the gene encoding the multidrug resistance protein-1 (MRP1). These results increase our understanding of how T-DXd resistance develops and may help oncologists tailor treatment plans for breast cancer patients accordingly.

Additional Presentations Reveal Potential Impact of Comprehensive Molecular Profiling
Poster and abstract summaries highlighting the Caris research presented at SABCS 2024 will be available onsite at Caris’ Booth #1217. The full abstracts will be available on the Caris website at the event’s conclusion.

Molecular landscape of HR+/HER2- male breast cancer (MaBC) compared with female breast cancer (FeBC) (Presentation Number: P1-01-16)
This study aimed to identify the molecular and immune differences between HR+/HER2- male and female breast cancer. NGS-based analysis of more than 8,200 breast cancer samples indicated that HR+/HER2- male breast cancer has a distinct mutational and immunological profile compared to its female counterpart. These findings suggest important differences in tumor biology between men and women with HR+/HER2- breast cancer. A better understanding of these differences may help in the design of future clinical trials and the development of treatments for men with HR+/HER2- breast cancer.

Spliceosome Mutations (Smut) in Metastatic Breast Cancer (MBC): An Analysis of a De-centralized Clinical Trial and Large Clinical-Genomic Dataset (Presentation Number: P1-01-20)
In this study, spliceosome mutations were analyzed in metastatic breast cancer (MBC) using data from the PRISMM (Patient Response to Immunotherapy using Spliceosome Mutational Markers) trial and Caris’ large clinical-genomic dataset. This analysis found that patients with spliceosome mutations do not have significant responses to immunotherapy. HR+/HER2- MBC had the highest frequency of spliceosome mutations and was associated with genomic aberrations of endocrine resistance, an immune-cold phenotype, and worse overall survival. These findings underscore the importance of molecular profiling in patients with MBC.

Prognostic implications of oncogenetic pathway alterations in advanced male breast cancer(Presentation Number: P1-05-21)
Male breast cancer has a distinct molecular and immune landscape compared to female breast cancer, but the prognostic implications of these differences have previously been unclear. In this study, 17,759 breast tumors were tested using WES and WTS to assess the effect of gene alterations on male breast cancer-related survival. Results showed that select genomic alterations have different prognostic significance in male and female breast cancer, suggesting that breast cancer in men may have a unique trajectory that differs from female breast cancer. Further investigation of sex-defined differences in breast cancer may help tailor future therapeutic strategies.

Comprehensive characterization of androgen receptor in male breast cancer (Presentation Number: P1-03-22)
While the estrogen receptor (ER) is well-studied in breast cancer, the role of the androgen receptor (AR) is less understood, particularly in male patients. This study aimed to characterize the molecular and immunological features associated with AR gene expression in male breast cancer. Comprehensive molecular profiling revealed that specific genomic alterations and immune markers are associated with AR expression. Further investigations of these features may assist in clinical trial design for men with breast cancer.

Molecular and immunological characterization of HER2-low, HER2 ultra-low, and HER2-null male breast cancer (Presentation Number: P3-01-25)
This final study aimed to determine whether there are differences in molecular and immunological features between HER2-low, HER2-ultra-low and HER2-null/negative breast cancer in males. Generally, these three HER2 subtypes in men shared genomic features, suggesting that their disease biology may be similar across the spectrum of what historically has been considered HER2-negative disease. Differences were noted, however, between these HER2 subtypes in their tumor immune microenvironments and warrant further investigation. These findings expand our current understanding of the HER2 spectrum in male breast cancer.
The Caris POA includes 96 cancer centers, academic institutions, research consortia and healthcare systems, including 47 NCI-designated cancer centers, who collaborate to advance precision oncology and biomarker-driven research. Caris and POA members work together to establish and optimize standards of care for molecular testing through innovative research focused on predictive and prognostic markers that improve the clinical outcomes for cancer patients.

On December 2, 2024 Rakovina Therapeutics Inc. (TSX-V: RKV, the "Company" or "Rakovina Therapeutics"), a biopharmaceutical company committed to advancing new cancer therapies based on novel DNA-damage response technologies, reported that its previously announced private placement has been further upsized to $3 million, based on strong indications of interest from potential investors in the financing (Press release, Rakovina Therapeutics, DEC 2, 2024, View Source;utm_medium=rss&utm_campaign=rakovina-therapeutics-increases-private-placement-offering-to-3-0-million [SID1234648760]).

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The Offering is structured as units priced at $0.06 each, with each unit consisting of one common share and one warrant to purchase a common share. Each warrant entitles the holder to purchase one additional common share at a price of $0.10 per share, exercisable for a period of 24 months. Rakovina retains the right to accelerate the warrant exercise period if the 20-day volume-weighted average price of its shares exceeds $0.30.

The Company plans to use the proceeds to continue the discovery and advancement of novel cancer treatments by leveraging collaborations with two proprietary Artificial Intelligence (AI) platforms: the Deep Docking AI platform and the Variational AI Enki Platform. The Company also plans to continue the development of its kt-3000 series through collaborations and partnerships with biotech and pharma companies.

The Offering is subject to all necessary regulatory approvals, including acceptance from the TSX Venture Exchange. The Units will be sold on a non-brokered "private placement" basis in accordance with applicable Canadian securities laws and under applicable exemptions from prospectus and registration requirements, and the securities will be subject to resale restrictions for a period of four months plus one day from the date of issue.

On December 2, 2024 Evaxion Biotech A/S (NASDAQ: EVAX) ("Evaxion"), a clinical-stage TechBio company specializing in developing AI-Immunology powered vaccines, reported that it will present preclinical Proof-of-Concept for its precision cancer vaccine concept, targeting non-conventional ERV (endogenous retrovirus) tumor antigens shared across patients at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress, taking place from December 11-13, 2024, in Geneva, Switzerland (Press release, Evaxion Biotech, DEC 2, 2024, View Source [SID1234648746]).

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The data to be presented stems from studies in human cells and mouse tumor models. The studies investigated human T-cell responses and mouse tumor growth inhibition induced by precision ERV vaccine targets identified using Evaxion’s AI-Immunology platform.

AI-Immunology can select ERV antigens for precision therapeutic cancer vaccines, offering therapeutic options for multiple specific cancer types and potentially enabling treatment for patients who are unresponsive to conventional cancer immunotherapy.

The new concept of deploying ERVs as vaccine targets allows for designing precision cancer vaccines that could be effective across diverse immune system characteristics, making them suitable for a wide range of patients. Evaxion plans to utilize this now preclinically validated concept to design new precision vaccine candidates to complement our existing pipeline of personalized cancer vaccines.

Conference presentation details:

Abstract title: AI-designed cancer vaccines: antigens from the dark genome are promising cancer vaccine targets
Poster#: 124P
Location: Foyer Mezzanine
Date/Time: December 12, 2024, at 12.30 CET/06.30 EST
Presenter: Daniela Kleine-Kohlbrecher, Senior Project Manager at Evaxion

On December 2, 2024 Agendia, Inc. reported the publication of a pivotal secondary analysis from the IDEAL randomized Phase 3 clinical trial in JAMA Network Open (Press release, Agendia, DEC 2, 2024, View Source [SID1234648742]). The study highlights the ability of the MammaPrint (MP) genomic assay to predict benefit of extended endocrine therapy (EET) in post-menopausal patients with early-stage, hormone receptor positive (HR+) breast cancer.

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The published study, titled Selection of Patients with Early-Stage Breast Cancer for Extended Endocrine Therapy: A Second Analysis of the IDEAL Randomized Clinical Trial, corroborates prior findings published from the NSABP B-42 trial, demonstrating that MP can identify patients who benefit most from EET and those with minimal benefit who can avoid associated side effects, thus optimizing adjuvant treatment decisions beyond traditional clinical risk factors.

This secondary analysis focused on MammaPrint’s predictive capacity of EET in preventing late recurrences among a translational cohort of 515 IDEAL patients. The cohort consisted of post-menopausal, hormone receptor-positive early breast cancer patients who were randomized to receiving 2.5- or 5-years of extended letrozole therapy after completing an initial 5 years of endocrine therapy. The original study did not show any benefit of 5 years over 2.5 years of endocrine therapy, however, through analysis using genomic profiling with MammaPrint, this study was able to identify a subset of patients who will benefit from EET. Key findings from the study include:

Significant benefit for MP Low-Risk Patients: MP Low-Risk patients derived the largest benefit from extended letrozole treatment at 10 years post-randomization. Researchers found an absolute benefit of 10.1% for distant recurrence (DR), 11.7% for recurrence-free interval (RFI), and 9.7% for breast cancer-free interval (BCFI) for MP Low-Risk patients. The effect of letrozole on the 10-year RFI rate was significantly dependent on MammaPrint classification.
No EET Benefit for MP High-Risk Patients: Patients with MP High-Risk tumors are more likely to relapse within the first 5 years of diagnosis and as evidenced by the results of the study, derive less benefit from extending endocrine therapy beyond the initial 5-years post-diagnosis.
Ultra-Low-Risk Findings: Although few patients in the cohort had a MP Ultra-Low tumor, they did not derive any EET benefit for the above endpoints, which is consistent with B42 where a larger number of ultralow patients were analyzed.
"By demonstrating MammaPrint’s ability to predict the benefit from extended endocrine therapy based on genomic risk, particularly the recurrence-free interval for Low-Risk patients, physicians are now better equipped to identify which patients will benefit from this treatment," said Laura van ‘t Veer, PhD, Professor of Laboratory Medicine, Co-Leader of the Breast Oncology Program and Director of Applied Genomics at the Helen Diller Family Comprehensive Cancer Center, University of California, Chief Research Officer and Co-Founder of Agendia. "These findings provide clinicians with a powerful tool to optimize endocrine treatment duration, potentially sparing MP High-Risk patients from unnecessary extended therapy while ensuring MP Low-Risk patients receive the full protective benefits they need."

"These data build upon the evidence gathered from the NSABP-42 study, providing further validation of MammaPrint’s genomic profiling to help refine treatment strategies and identify patients who are more likely to benefit from extended endocrine therapy," said William Audeh, MD, MS, Chief Medical Officer of Agendia. "We know that some hormone-positive breast cancer may have a risk for late recurrences, beyond five years, and these data show that MammaPrint can predict which of those recurrences are preventable by EET. Because MammaPrint looks at the biology of the tumor early in the treatment cycle, it can distinguish Low-Risk patients who will derive substantial benefit from extended endocrine therapy from High-Risk patients who will not. This approach not only optimizes therapeutic efficacy, but also minimizes unnecessary treatment for those unlikely to benefit, thereby enhancing overall patient care."

The data from both IDEAL and NSABP-B42 validate MP’s predictive ability to determine which patients will benefit from EET and which can avoid it, potentially improving long-term survival outcomes and quality of life. These findings expand MP’s clinical utility beyond guiding neoadjuvant and adjuvant chemotherapy decisions and towards optimizing the duration of adjuvant endocrine treatment.

On December 2, 2024 Zai Lab Limited (Nasdaq: ZLAB; HKEX: 9688) and Novocure (NASDAQ: NVCR) reported that the pivotal, Phase 3 PANOVA-3 trial met its primary endpoint, demonstrating a statistically significant improvement in median overall survival (mOS) versus control. PANOVA-3 evaluated the use of Tumor Treating Fields (TTFields) therapy concomitantly with gemcitabine and nab-paclitaxel as a first-line treatment for unresectable, locally advanced pancreatic adenocarcinoma (Press release, Zai Laboratory, DEC 2, 2024, View Source [SID1234648741]).

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"As a researcher and clinician, I have experienced the challenges of developing treatments in pancreatic cancer. It is exciting to see the PANOVA-3 trial achieve the positive primary endpoint of overall survival, a landmark outcome for this field," said Vincent Picozzi, M.D., medical oncologist and investigator in the PANOVA-3 trial. "These data for Tumor Treating Fields are very promising, especially in this difficult to treat patient population."

In the intent-to-treat population, patients treated with TTFields therapy concomitant with gemcitabine and nab-paclitaxel had an mOS of 16.20 months compared to 14.16 months in patients treated with gemcitabine and nab-paclitaxel alone, a statistically significant 2.0-month improvement (hazard ratio=0.819; P=0.039) (N=571). The survival rate benefit for patients treated with TTFields therapy increased over time with a 13% improvement in the overall survival rate at 12 months and a 33% improvement in survival rate at 24 months. TTFields therapy was well-tolerated, and safety was consistent with prior clinical studies.

"PANOVA-3 is the first and only Phase 3 trial to demonstrate a statistically significant benefit in overall survival specifically in unresectable, locally advanced pancreatic cancer, and is Novocure’s third positive Phase 3 clinical trial in the last two years," said Nicolas Leupin, M.D., PhD, Chief Medical Officer, Novocure. "We are grateful to the patients and investigators for their participation in the trial, and we look forward to sharing the full data at an upcoming medical conference."

"There are approximately 134,000 new cases of pancreatic cancer diagnosed annually in China, and this cancer is one of the most challenging to treat globally, with limited effective treatment options and poor survival outcomes," said Dr. Rafael Amado, M.D., President, Head of Global Research and Development at Zai Lab. "Demonstrating a statistically significant and clinically meaningful improvement in overall survival for patients with unresectable, locally advanced pancreatic cancer is an important achievement. We are pleased to have been able to contribute to the PANOVA-3 study, and we look forward to working with Novocure to bring this therapy to patients as soon as possible."

Novocure plans to file for regulatory approval of TTFields in unresectable, locally advanced pancreatic adenocarcinoma based on PANOVA-3 and plans to submit the PANOVA-3 results for presentation at an upcoming medical congress. Zai Lab plans to file for regulatory approval in China.

About PANOVA-3

PANOVA-3 is a prospective, randomized open-label, controlled Phase 3 clinical trial designed to test the efficacy and safety of Tumor Treating Fields (TTFields) therapy used concomitantly with gemcitabine and nab-paclitaxel, as a first-line treatment of locally advanced pancreatic adenocarcinoma. Patients were randomized to receive either TTFields therapy concomitant with gemcitabine and nab-paclitaxel or gemcitabine and nab-paclitaxel alone.

The primary endpoint is overall survival. Secondary endpoints include progression free survival, local progression free survival, objective response rate, one-year survival rate, quality of life, pain-free survival, puncture-free survival, resectability rate, and toxicity.

A total of 571 patients were enrolled in the study, randomized 1:1 and followed for a minimum of 18 months.

About Pancreatic Cancer in China

Pancreatic cancer is one of the most common and deadliest cancers globally. In China, there were an estimated 134,374 new cases in 2022, and it is now the eighth most common cancer type1. The current median survival of patients with locally advanced, unresectable pancreatic cancer is nine to twelve months, and the five-year survival rate was 7.2%2, making it the malignancy with the lowest survival rate in China.

About Tumor Treating Fields

Tumor Treating Fields (TTFields) are electric fields that exert physical forces to kill cancer cells via a variety of mechanisms. TTFields do not significantly affect healthy cells because they have different properties (including division rate, morphology, and electrical properties) than cancer cells. These multiple, distinct mechanisms work together to target and kill cancer cells. Due to these multimechanistic actions, TTFields therapy can be added to cancer treatment modalities in approved indications and demonstrates enhanced effects across solid tumor types when used with chemotherapy, radiotherapy, immune checkpoint inhibition, or targeted therapies in preclinical models. TTFields therapy provides clinical versatility that has the potential to help address treatment challenges across a range of solid tumors.

To learn more about TTFields therapy and its multifaceted effect on cancer cells, visit tumortreatingfields.com.