On June 27, 2024 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA (cfDNA) and genetic testing, reported a new gastroesophageal cancer trial, DECIPHER, that will utilize the company’s personalized and tumor-informed molecular residual disease (MRD) test, Signatera, to guide patient selection and assess the rate of MRD clearance in patients being treated for gastroesophageal cancer (Press release, Natera, JUN 27, 2024, View Source [SID1234644590]).

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DECIPHER (Developing ctDNA Guided Adjuvant Therapy for Gastroesophageal Cancer) is a single-arm, open-label phase II trial, and the first trial to evaluate the efficacy of a HER2-directed antibody-drug conjugate in gastroesophageal adenocarcinoma (EGC) patients in the adjuvant setting. The study plans to enroll 25 patients from more than 10 sites across the United Kingdom. Patients who are Signatera-positive following neoadjuvant chemotherapy and surgery will forgo standard-of-care adjuvant chemotherapy and receive the investigational therapy for a maximum of eight cycles. Signatera will be used to measure MRD-positivity following surgery and serially thereafter, with MRD clearance serving as the primary endpoint.

"With an adaptive approach aimed at eliminating MRD, DECIPHER is designed to offer patients a second chance at a cure when they have not responded to standard of care therapies," said Dr. Elizabeth Smyth, M.D., consultant in medical oncology at Oxford University Hospitals NHS Foundation Trust l and chief investigator of the trial. "Signatera’s personalized, tumor-informed approach, which has demonstrated high sensitivity across several different cancer types including EGC, will be a key component of this study."

This launch of DECIPHER follows data from the PLAGAST study presented last month at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The data showed that EGC patients who were Signatera-positive following neoadjuvant FLOT (fluorouracil, leucovorin, oxaliplatin and docetaxel) chemotherapy and surgical resection were at an extremely high risk of disease progression by 12 months, despite standard of care adjuvant treatment, and had a 24-month overall survival rate of zero.1

Gastroesophageal cancer is a common global cancer that has sustained a nearly 2.5-fold increase in incidence over the last two decades.1 Patients with early-stage disease are typically treated with neoadjuvant chemotherapy, followed by surgery and adjuvant chemotherapy. Despite this aggressive and multimodal approach, treatment is curative in less than 50 percent of patients.2

"We are pleased to work with leading investigators in the UK on the first interventional trial for Signatera in gastroesophageal cancer," said Adham Jurdi, M.D., senior medical director of oncology at Natera. "With DECIPHER, we aim to demonstrate how the pairing of Signatera with innovative therapies can potentially enable new personalized treatment options and ultimately improve outcomes for EGC patients."

DECIPHER will be featured today, June 27, 2024, in a poster at the European Society for Medical Oncology Gastrointestinal Cancers (ESMO GI) Congress 2024 in Munich, Germany. The poster is entitled, "A single arm phase II trial of trastuzumab deruxtecan in patients with gastro-oesophageal adenocarcinoma cancer who are ctDNA and HER2 positive: DECIPHER".

About Signatera

Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard of care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer, ovarian cancer and muscle invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in more than 60 peer-reviewed papers.

On June 27, 2024 REVEAL GENOMICS, S.L., a Barcelona-based biotechnology start-up seeking to revolutionize precision oncology through biomarker innovation, reported the results of the study "HER2DX ERBB2 mRNA assay Following Trastuzumab-Based Chemotherapy in HER2-Positive Advanced Gastric Cancer" presented at ESMO (Free ESMO Whitepaper) Gastrointestinal Cancers Congress 2024 in Munich, showing that HER2DX genomic test demonstrates significant potential in refining patient selection for trastuzumab-based chemotherapy in HER2-positive advanced gastric cancer (Press release, REVEAL GENOMICS, JUN 27, 2024, View Source [SID1234644589]).

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HER2+ advanced gastric cancer treatment shows variable response to trastuzumab plus chemotherapy, indicating the need for precise biomarkers. The HER2DX is a promising tool for enhancing patient selection by quantifying ERBB2 mRNA expression levels, and classifying tumor samples into different groups: low, medium, and high.

Patricia Villagrasa, REVEAL GENOMICS’ CEO, says, "This study marks the first time that HER2DX has been applied outside of breast cancer, illustrating its precision and potential across different oncological applications. Our findings underscore the test’s capability to improve patient selection, fundamentally transforming the treatment approach for those battling advanced gastric cancer. This represents a significant milestone in our ongoing commitment to advance personalized medicine."

Dr. Tamara Saurí, medical oncologist, coordinator of upper- gastrointestinal cancers, and principal investigator of the study at Hospital Clinic of Barcelona, stresses: "Advanced HER2+ gastric cancer treatment shows variable response to trastuzumab plus chemotherapy, indicating the need for precise biomarkers. HER2DX not only addresses a crucial unmet need but also explains why HER2-positive gastric cancers often have poorer responses compared to HER2-positive breast cancers. By revealing tumor diversity and expression patterns, the test might guide the development of more effective, personalized treatment strategies. This insight is crucial as we explore novel anti-HER2 therapies alone or in combination, aiming to improve patient outcomes."

HER2DX: beyond breast cancer
The study utilized the HER2DX genomic test with a focus on the ERBB2 score to evaluate its association with survival outcomes. The HER2DX genomic test was evaluated in 60 patients with HER2+ advanced gastric cancer treated at two hospitals in Spain (Hospital Clinic of Barcelona and Hospital General Granollers).

The study highlighted the test’s effectiveness, showing a hazard ratio of 0.38 for PFS, indicating a 62% reduction in the risk of progression for patients with high ERBB2 mRNA levels compared to those with low levels. Additionally, the hazard ratio for OS was 0.53, reflecting a 47% reduction in the risk of death for patients in the high ERBB2 mRNA group compared to the low group.

Comparative Analysis with Breast Cancer
The study also included a comparative analysis of ERBB2 expression between gastric and breast cancers, revealing generally lower levels of ERBB2 in gastric cancer, including within the HER2 +3 immunohistochemical category. This comparison further highlights the nuanced role of ERBB2 across different cancers and the need for better methods to quantify this target.

About HER2DX️
HER2DX️ is the world’s first diagnostic test formulated specifically for HER2+ breast cancer. Marketed by REVEAL GENOMICS️ since January 2022, the HER2DX is a standardized 27-gene expression test for patients with early-stage HER2+ breast cancer.

HER2DX️ is a prognostic and predictive assay based on clinical and genomic data. The test integrates clinical information (i.e., tumor size and nodal status) with biological information tracking immune response, luminal differentiation, tumor cell proliferation, and expression of the HER2 17q12-21 chromosomal amplicon, including the ERBB2 gene.

HER2DX️ predicts:

Risk of relapse score (high vs. low): the risk of recurrence in patients with newly diagnosed HER2+ breast cancer.
pCR likelihood score (high vs. medium vs. low): the likelihood of a patient responding to anti-HER2-based treatment before surgery.
ERBB2 score (high vs. medium vs. low): the quantitative expression of ERBB2 mRNA across HER2-negative, HER2-low and HER2+ breast cancer.
About GASTRIC CANCER
According to the article "The current and future incidence and mortality of gastric cancer in 185 countries, 2020−40: A population-based modeling study" published online by eClinicalMedicine in 2022: "In total, approximately 1.1 million new cases and 770,000 deaths of gastric cancer were estimated in 2020. Incidence rates were on average 2-fold higher in males than females (15.8 and 7.0 per 100,000, respectively) with variation across countries. The annual burden of gastric cancer is predicted to increase to approximately 1.8 million new cases and 1.3 million deaths by 2040."

On June 27, 2024 EditCo Bio, Inc., a leader in genome engineering innovation, reported the expansion of its T-cell editing portfolio with the launch of Knockout CD8+ T-cell Pools (Press release, EditCo Bio, JUN 27, 2024, View Source [SID1234644588]). This new addition builds upon the success of their Knockout CD4+ T-cell Pools, offering researchers an advanced tool for primary T-cell editing that brings unprecedented precision and scalability to cancer and immunotherapy research.

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Leveraging EditCo Bio’s cutting-edge automated platform, the new Knockout CD8+ T-cell Pools allow researchers to bypass challenging optimization steps and access highly functional edited T-cells ready for immediate use. This innovation accelerates the transition from research discovery to clinical application and delivers several key benefits:

Accelerated results: EditCo Bio’s unique 7-day protocol and proprietary guide RNA technology achieve knockout efficiencies approaching 100% in primary human CD8+ T-cells. Additionally, EditCo has several prescreened and optimized donor cells available to kick off projects immediately.
Dependable performance: Edited CD8+ T-cell pools demonstrate exceptional editing efficiency (~100%) and viability (>85%). with editing efficiency unchanged for at least 4 weeks in culture.
Enhanced functionality: Edited CD8+ T-cell pools showed antigen-specific CD107a mobilization, a hallmark of cytotoxic activity.
Customizable solutions: EditCo Bio can efficiently onboard customer-supplied donor cells, ensuring high knockout efficiencies, viability, and turn-around times tailored to specific project needs.
"For researchers working on the front lines of immunotherapy, having access to high-quality CD8+ T-cells can significantly accelerate the pace of discovery and therapeutic development," said Travis Maures, CSO of EditCo Bio. "Our new Knockout CD8+ T-cell Pools provide the precision, efficiency, and scalability needed to push the boundaries of what’s possible in cellular research."

The addition of Knockout CD8+ T-cell Pools further strengthens EditCo Bio’s comprehensive Engineered Cell portfolio, solidifying its position as a leader in cell engineering solutions. The company plans to continue to expand its range of edited primary cell products to include other primary cell subsets, which will be available later this year.

For more information regarding EditCo Bio’s Knockout T-cell Pools, visit www.EditCo.bio/contact.

On June 27, 2024 Abdera Therapeutics Inc., a biopharmaceutical company leveraging its advanced antibody engineering ROVEr platform to design and develop tunable, precision radiopharmaceuticals for cancer, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to ABD-147 for the treatment of patients with extensive stage small cell lung cancer (ES-SCLC) who have progressed on or after platinum-based chemotherapy (Press release, Abdera Therapeutics, JUN 27, 2024, View Source [SID1234644587]). ABD-147 is a next-generation precision radiopharmaceutical biologic therapy designed to deliver Actinium-225 (225Ac) to solid tumors expressing DLL3, a protein found on the surface of neuroendocrine tumors, but rarely expressed on the surface of normal cells or tissues.

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The FDA’s Fast Track program is designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Clinical programs with Fast Track designation may benefit from early and frequent communication with the FDA throughout the regulatory review process and may also be eligible for Accelerated Approval and Priority Review if relevant criteria are met.

"Aggressive neuroendocrine cancers such as SCLC carry a poor prognosis and new treatment options are urgently needed," said Lori Lyons-Williams, president and chief executive officer. "These cancers have the most aggressive clinical course of any type of pulmonary tumor and often rapidly metastasize to other parts of the body. We are thrilled the FDA has recognized the potential of ABD-147 to become a transformative treatment option for SCLC and we are excited to begin clinical development and provide ABD-147 to patients in need."

In the second half of 2024, Abdera plans to initiate a first-in-human Phase 1 clinical trial with ABD-147 in patients with SCLC or large cell neuroendocrine carcinoma (LCNEC) who previously received platinum-based therapy.

About Small Cell Lung Cancer and Large Cell Neuroendocrine Carcinoma

The global incidence for SCLC and LCNEC has been reported to represent approximately 325,000 patients and is expected to increase 4% annually through 2029. In the U.S., the incidence has been reported to be approximately 35,000 new cases annually. Fifteen percent of all lung cancer cases are high-grade neuroendocrine cancers. These cancers have the most aggressive clinical course of any type of pulmonary tumor and often metastasize to other parts of the body, including the brain, liver and bone. Without treatment, the median survival from diagnosis has been reported to be only two to four months. With treatment, the overall survival at five years is 5% to 10% for SCLC, and 15% to 25% for LCNEC. SCLC and LCNEC generally carry a poor prognosis and new treatment options are urgently needed.

About ABD-147

ABD-147 is a targeted radiopharmaceutical biologic therapy designed to deliver Actinium-225 (225Ac), a highly potent alpha-emitting radioisotope, to solid tumors expressing delta-like ligand 3 (DLL3) with high affinity. DLL3 is a protein in the Notch pathway that is critical for the development and regulation of neuroendocrine versus epithelial cell differentiation in the lungs. In certain high grade neuroendocrine carcinomas including small cell lung cancer (SCLC), DLL3 is upregulated and specifically expressed on the cell surface in more than 80% of cases. In contrast, DLL3 is absent or very rarely expressed on the surface of nonmalignant cells. Given the high specificity of DLL3 expression on cancer cells and the distinct mechanism of action, DLL3 represents a compelling target for treating SCLC and other DLL3+ solid tumors with targeted radiotherapy.

About the ROVEr Platform

Abdera’s Radio Optimized Vector Engineering (ROVEr) platform enables the company to custom-engineer targeted radiopharmaceuticals with tunable pharmacokinetic (PK) properties to achieve high tumor uptake while minimizing renal exposure and mitigating other systemic radiotoxicities such as myelosuppression. Abdera can optimize the delivery and therapeutic index of potent radioisotopes capable of emitting powerful alpha or beta particles to selectively destroy tumor cells while sparing healthy cells, providing patients with potentially transformative new cancer treatments.

Abdera’s approach offers the ability to design radiotherapeutics against virtually any cancer target expressed on the cell surface. Coupled with a highly potent mechanism of cell killing, the ROVEr platform is uniquely poised to exploit both high- and low-expressing targets to selectively deliver therapeutic levels of radioisotope to cancer cells.

On June 27, 2024 Abbisko Therapeutics Co., Ltd. (Abbisko Therapeutics) reported that it has presented new phase II clinical data of its highly selective FGFR4 inhibitor irpagratinib (ABSK011) in combination with atezolizumab for the treatment of advanced hepatocellular carcinoma（HCC）at the 2024 ESMO (Free ESMO Whitepaper)-GI Congress (Press release, Abbisko Therapeutics, JUN 27, 2024, View Source [SID1234644586]). The presentation highlights that 220mg BID of irpagratinib in combination with atezolizumab demonstrated promising antitumor activity with an objective response rate (ORR) of 50% in FGF19+ HCC patients.

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ESMO-GI, a world-renowned gastrointestinal oncology conference, is being held in Munich, Germany, from June 26 to 29, 2024.

Abbisko presentations at ESMO (Free ESMO Whitepaper)-GI 2024:

Title: A Phase 2 Study of Irpagratinib (ABSK-011) plus Atezolizumab in Patients with Advanced Hepatocellular Carcinoma (HCC)
Poster display number：171P
Poster display session: Hepatocellular and non-biliary liver cancer
Poster display date and time: 27 June 2024, 15:35-16:30 PM (UTC+1)

Summary:

At the 2024 ESMO (Free ESMO Whitepaper)-GI conference, Abbisko Therapeutics debuted new clinical trial results with the combination of irpagratinib and atezolizumab. In HCC patients with FGF19 overexpression, the objective response rate (ORR) was 50% (5/10)in the 220 mg BID cohort, demonstrating this novel combination therapy has notable benefits in enhancing the ORR. Notably, strong efficacy and good safety were also observed in patients who had previously received immune checkpoint inhibitor (ICI) therapy, providing further evidence that targeting FGF19-FGFR4 may provide a much-needed differentiated treatment option for HCC.

Given the encouraging preliminary results from this study, Abbisko plans to explore dual/triple combinations with irpagratinib in earlier lines of therapy for HCC. Abbisko continues to look forward to combination approaches with irpagratinib to better address HCC and bring hope to patients, with aims to conduct further research and innovation in this area.

Background:

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and ranks as the sixth most prevalent cancer and third leading cause of death worldwide. Dysregulation of FGF19-FGFR4 signaling accounts for approximately 30% of HCC and plays a pivotal role in driving HCC tumorigenesis. Irpagratinib is a highly potent and selective FGFR4 inhibitor, with potential to become a first-in-class or best-in-class FGFR4 inhibitor. Abbisko Therapeutics previously presented clinical data from its first-in-human study of irpagratinib at the 2023 ESMO (Free ESMO Whitepaper) Annual Meeting, demonstrating promising anti-tumor activity as a single agent with an ORR of 40.7% in FGF19 overexpressed late-line HCC patients.

To further explore the therapeutic potential of irpagratinib, Abbisko is conducting a phase 2 clinical trial of irpagratinib in combination with atezolizumab. This trial is investigating irpagratinib in combination with atezolizumab, a PD-L1 antibody, in FGF19+ advanced HCC patients, to understand safety and efficacy.