On January 23, 2025 EXUMA Biotech, Corp., a clinical-stage biotechnology company discovering and developing cell and gene immunotherapies for solid and hematological malignancies, reported clinical data from a completed Phase 1 trial evaluating a novel autologous HER2-targeted CAR-T therapy (Press release, EXUMA Biotech, JAN 23, 2025, View Source [SID1234649859]). The data presented today at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, highlights promising efficacy and safety for autologous engineered human T cells that target cancer via a proprietary chimeric antigen receptor (CAR) designed to selectively target HER2 in the tumor microenvironment (TME).

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The single center, investigator-initiated, dose escalation trial enrolled 12 patients with HER2-positive Stage IV solid tumor malignancies, including three gastric, one esophageal, four colorectal, and four breast cancers. Patients received a single dose of CAR-T cells (3E5, 1E6, or 1E7 CAR+ cells/kg) from a peripheral blood draw-derived 12-day manufacturing process (17 days to product release) following lymphodepletion with cyclophosphamide and fludarabine. No manufacturing failures occurred.

Key Findings:

Safety: No dose limiting toxicities or investigational-product related serious adverse events. No adverse events leading to study discontinuation. One patient experienced Grade 2 cytokine release syndrome (CRS), which resolved. No ICANs or any other CNS toxicities occurred. No on-target, off-tumor toxicity (OTOTT) was detected with longitudinal clinical and laboratory assessments.
Efficacy: A deep PR (100% reduction in SLD) was observed in a gastroesophageal cancer patient that was ongoing at 36 weeks of follow-up. Cohort 3’s 12-month survival rate was 80%, compared to 45.5% for all three dose cohorts combined.
Wendy Li, MD Chief Medical Officer of EXUMA Biotech, remarked, "There continues to be a need for treatments with the potential to safely elicit frequent deep and durable responses in HER2 positive gastroesophageal cancer patients through different mechanisms of action. We administered the maximum feasible dose, which delivered clear anti-tumor activity in patients without OTOTT or dose limiting toxicities. Our team is now focused on patients with HER2 positive gastroesophageal malignancies, particularly in Asia, where the incidence of gastroesophageal cancers contributes significantly to morbidity and mortality."

Abstract Title: Clinical results of a phase 1 trial evaluating a HER2 directed CAR-T product selective for the tumor microenvironment (TME) in patients with GI and other solid tumor malignancies
Abstract ID: 449
Poster #: F14

About CCT303-406
CCT303-406 is EXUMA Biotech’s TMR autologous CAR-T product candidate targeting HER2, which has completed an investigator-initiated clinical trial in patients with metastatic HER2+ solid tumors. HER2 overexpression is a hallmark of several tumors, including those originating from breast, stomach, bladder, and colon. Patients relapse or become unresponsive to antibody-based regimens targeting HER2 in early lines of treatment yet may still retain overexpression of HER2. CCT303-406 has clinically shown to be a promising option for gastroesophageal patients providing T cell-mediated antitumor activity via targeting HER2. Differentiated from other HER2 CAR-T therapies, CCT303-406 incorporates EXUMA’s TMR targeting technology, focusing CAR-T activity to the TME, thereby reducing the risk of on-target, off-tumor toxicity.

GCAR and SCL Update
EXUMA plans to complete non-human primate (NHP) studies in support of its 1st in vivo CAR-T product, GCAR and SCL mRNA LNP technology in 1H25. Studies will assess vector selectivity (tropism), biodistribution, pharmacokinetics, pharmacodynamics and safety as well as the influence of SCL mRNA administration on GCAR cellular PK. Results from these studies will inform regulatory discussions for IND enabling activities in the US for its 1st GCAR product for clinical investigation.

"We are pleased with these data that support our decade-long vision to expand the safety and efficacy of CAR-T into solid tumors," stated Gregory Frost, Ph.D. Chairman and CEO of EXUMA Biotech. "Towards the second and equally important dimension of this vision, we look forward to advancing these and other CARs into clinical investigation with our in vivo GCAR platform, enabled by EXUMA’s novel FITNESS DRIVER and CD3-targeted and synthetic car ligand (SCL) technologies, having the potential to provide a truly off-the-shelf solution for patients."

On January 23, 2025 Rakuten Medical, Inc., a global biotechnology company developing and commercializing precision, cell-targeting Alluminox platform-based photoimmunotherapy, reported the initiation of its global multi-regional Phase 3 clinical trial evaluating ASP-1929 photoimmunotherapy in combination with anti-PD-1 (pembrolizumab) as a first-line therapy for recurrent head and neck squamous cell carcinoma (HNSCC) (Protocol number: ASP-1929-381 / Acronym: ECLIPSE* / ClinicalTrials.gov Identifier: NCT06699212) (Press release, Rakuten Medical, JAN 23, 2025, View Source [SID1234649858]). The first patient in this trial recently received a study treatment at the Avera Cancer Institute in Sioux Falls, South Dakota, USA. Alongside the U.S., patient enrollment is slated for sites in Japan and Taiwan, followed by additional countries and regions.

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The ASP-1929-381 study is a multi-regional multi-center, randomized, open-label Phase 3 trial, designed to assess the efficacy and safety of ASP-1929 photoimmunotherapy in combination with pembrolizumab as a first-line treatment for locoregional recurrent HNSCC without distant metastases. Approximately 400 patients globally will be randomized to either an experimental arm receiving ASP-1929 photoimmunotherapy in combination with pembrolizumab, or a control arm receiving the current pembrolizumab-based standard of care (SOC), where patients may receive pembrolizumab alone or in combination with chemotherapy according to the physician’s choice.

The primary endpoint is Overall Survival (OS), with key secondary endpoints including Complete Response Rate (CRR) and Overall Response Rate (ORR).

This study builds on data from an interim evaluation (data cut-off: August 31, 2023) of 19 patients enrolled in the HNSCC cohort of a prior Phase 1b/2 study (ASP-1929-181 study / ClinicalTrials.gov Identifier: NCT04305795). The data showed an estimated 24-month survival rate of 52.4%, with a median OS not yet reached, and a generally tolerated safety profile.

Head and neck cancer ranks as the 7th most common cancer globally with over 90% classified as squamous cell carcinoma1. More than 60% of HNSCC patients present with locally or regionally advanced disease (stage III or IV)1. Of these, 15-40% will experience recurrence, facing a poor prognosis and a 5-year overall survival rate of less than 50%1.

Dr. Kristen Coffroth, MD of Avera Medical Group Ear, Nose & Throat – Head and Neck Surgery, and one of the investigators for the ASP-1929-381 study at the Avera Cancer Institute, stated, "Photoimmunotherapy has a unique mode of action, which involves a biophysical disruption of targeted cells. Pembrolizumab has become a mainstay in systemic treatment for recurrent/metastatic HNSCC. This trial will evaluate whether the combination of ASP-1929 photoimmunotherapy with pembrolizumab can harness synergistic antitumor effects, which may shed new light on the treatment of locoregional recurrent HNSCC."

Dr. William Chad Spanos, MD, FACS of Avera Medical Group Ear, Nose & Throat – Head and Neck Surgery, and Principal Investigator for the ASP-1929-381 study at the Avera Cancer Institute, added, "I am impressed by the technology behind photoimmunotherapy, which offers a novel and targeted approach to cancer treatment. Combining this with pembrolizumab has the potential to expand first-line treatment options for patients with recurrent HNSCC. I am pleased to initiate this groundbreaking trial at our site and look forward to contributing to advancing care for patients facing this challenging disease."

Mickey Mikitani, Chief Executive Officer and Vice Chairman of the Board of Rakuten Medical, concluded, "The initiation of this global Phase 3 trial marks a significant milestone in our journey to contribute to the treatment and lives of patients with head and neck cancer and potentially others affected by cancer. With encouraging data from Phase 1b/2 study, we are optimistic about the potential of ASP-1929 photoimmunotherapy combined with pembrolizumab to improve treatment outcomes in recurrent head and neck cancer."

On January 23, 2025 CG Pharmaceuticals (CG Pharma), a clinical biopharmaceutical company located in the San Francisco Bay Area, established as an independent entity in 2024 after licensing ivaltinostat from CG Invites reported that it has since been conducting various research projects on ivaltinostat in the U.S. including the metastatic pancreatic cancer (mPDAC) clinical trial (NCT05249101) (Press release, CrystalGenomics, JAN 23, 2025, View Source [SID1234649857]). The results of the completed Phase 1b study and the progress report of Phase 2 will be presented at the ASCO (Free ASCO Whitepaper) Gastrointestinal Symposium on Friday, January 24.

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In the Phase 1b study, a total of 28 patients with locally advanced or metastatic PDAC who had received at least one prior line of therapy were administered ivaltinostat at 3 different dose levels (60, 125 and 250 mg/m² on days 1 and 8) in combination with capecitabine (1000 mg/m², administered twice daily on days 1-14) of a 21-day cycle.

Treatment-emergent adverse event (TEAE) profile was similar across dose levels, with the most common TEAEs (primarily grade 1-2) including fatigue, nausea, palmar-plantar erythrodysesthesias, constipation, and diarrhea. No serious adverse events that were related to ivaltinostat occurred in any of the 3 dose cohorts.

At the time of data cutoff (12/28/2024), there were 7 patients still alive, 18 deaths (all due to disease progression after discontinuation from study; no deaths directly related to study treatment), 1 patient lost to follow-up, and 2 study withdrawals. The longest-surviving patient has been alive for 27 months and the maximum duration of treatment was 20 months. Two thirds (65%) from a total of 28 patients showed stable disease or no evidence of disease, 14% experienced disease progression, and 22% were not evaluated.

The safety and efficacy results of the Phase 1b clinical study demonstrated that ivaltinostat can be effectively combined with cytotoxic chemotherapy to treat mPDAC. With the RP2D of ivaltinostat established at 250 mg/m2 from Phase 1b, this combination is now being evaluated in the Phase 2 randomized portion of the study comparing ivaltinostat plus capecitabine versus capecitabine alone in the maintenance setting for patients with mPDAC who underwent first line fluoropyrimidine-based therapy for at least four months without disease progression in terms of Progression-Free Survival and Overall Survival.

The ongoing Phase 2 trial began patient enrollment in January 2024 and has already achieved over 62% of its target enrollment across 17 U.S. clinical trial sites. CG Pharma anticipates completing Phase 2 patient enrollment and follow-ups this year, with a final clinical study report expected by mid-2026.

Ivaltinostat: A Promising New Approach

Ivaltinostat, an epigenetic-targeting HDAC inhibitor, has shown exceptional safety and pharmacokinetic profiles compared to other investigational agents in its class. Metastatic pancreatic cancer remains a deadly malignancy with limited treatment options, underscoring the urgent need for innovative therapies like ivaltinostat.

On January 23, 2025 Ymmunobio (YB) reported that they in collaboration with the Paul Scherrer Institute (PSI) have received Innosuisse support to develop innovative radioactive loaded antibodies for the treatment and diagnostic of solid tumors based on YBs proprietary YB-800 (Press release, Ymmunobio, JAN 23, 2025, View Source [SID1234649856]). The Innosuisse support validates Ymmunobio’s approach to targeted solid tumor therapy using a new and first in class target with a high prevalence in cancer patients.

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The newly developed antibodies will utilize a linker attached to YB-800, capable of carrying any radioactive isotope for the treatment and diagnostic of solid tumors. Ymmunobio plans to leverage this cutting-edge technology to treat patients with solid tumors who express the new marker. Radiolabeled antibodies will enhance physicians’ ability to diagnose using SPECT imaging while simultaneously targeting solid tumors that evade current therapies, paving the way for more personalized and effective treatment strategies.

Dr. Peter Schiemann, Ymmunobio CEO and Chair of the Board says: "The support by Innosuisse validates our novel and first in class approach to solid tumor treatment and improving patient outcomes through advanced diagnostic and therapeutic solutions.
We are proud to have received this Innosuisse validation and to have found an exceptional partner to co-develop these new treatment options for patients. Together, YB and PSI are pioneering advances in diagnostics and treatments in oncology, working towards a future where healthcare is more personalized, precise, and effective for all patients."

Dr. Martin Behe, project leader at PSI, is excited about project: "Radiolabeled compounds for cancer therapy and diagnosis have attracted significant attention from both physicians and the industry. Several of these radiopharmaceuticals have been successfully tested in clinical trials and are now routinely used in therapies, such as for prostate cancer. We are excited to collaborate with Ymmunobio in developing a radiolabeled antibody to further improve cancer treatment. This project is made possible with the support of Innosuisse."

Ymmunobio is at the forefront of oncology research, focusing on a novel target receptor for the treatment of solid tumors with high unmet need. Currently, in pre-clinical development, Ymmunobio’s research is dedicated to advancing three treatment options for GI cancers, with their innovative platform:

YB-800ADC carrying up to 8 payloads with a linker of the 3rd generation
YB-800R1 (therapeutic) and YB-800R2 (diagnostic) antibodies carrying radioactive isotopes in collaboration with PSI
YB-800BS, bi-specific antibodies with an aCD3 T-Cell engager.

On January 23, 2025 Lunit (KRX:328130.KQ), a leading provider of AI-powered solutions for cancer diagnostics and therapeutics, reported the publication of a new study in the Journal of Clinical Oncology Precision Oncology (Press release, Lunit, JAN 23, 2025, View Source;new-study-published-in-jco-precision-oncology-302358653.html [SID1234649855]). Conducted in collaboration with Japan’s National Cancer Center Hospital East (NCCHE), the study reveals how Lunit’s cutting-edge AI-powered pathology solutions, Lunit SCOPE HER2 and Lunit SCOPE IO, significantly improve HER2 biomarker evaluation and the prediction of clinical outcomes in metastatic colorectal cancer (mCRC) patients undergoing HER2-targeted therapy.

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This study presents findings from the TRIUMPH phase II clinical trial, which evaluated 30 patients with HER2-positive metastatic colorectal cancer treated with dual HER2-targeted therapy using Trastuzumab and Pertuzumab. Lunit’s AI solutions were applied to assess HER2 status and tumor microenvironment (TME) variables, with significant findings:

Enhanced HER2 Assessment Accuracy

Lunit SCOPE HER2 demonstrated 86.7% accuracy compared to pathologist assessments for HER2 immunohistochemistry (IHC), achieving 100% accuracy in identifying HER2 IHC 3+ cases.

Improved Prediction of Treatment Response and Outcomes

Patients identified by the AI model as having a high proportion of HER2 IHC 3+ staining tumor cells (AI-H3-high, >50%) exhibited better clinical outcomes than those identified through traditional HER2 evaluation methods:

Objective Response Rate (ORR): 42.1% (AI-H3-high) vs. 26.7% (overall TRIUMPH trial)
Progression-Free Survival (PFS): 4.4 months (AI-H3-high) vs. 1.4 months (AI-H3-low)
Overall Survival (OS): 16.5 months (AI-H3-high) vs. 4.1 months (AI-H3-low)
Deeper Insights into the Tumor Microenvironment (TME)

Using Lunit SCOPE IO, the study performed detailed TME profiling, including lymphocyte, macrophage, and fibroblast densities. Among AI-H3-high patients, those with low stromal TME density (TME-low) achieved the most favorable outcomes:

ORR: 57.1%
PFS: 5.6 months
OS: 26.0 months
The findings underscore the transformative potential of AI-powered pathology tools in precision oncology. By providing a more accurate and detailed evaluation of HER2 status and TME characteristics, Lunit’s solutions can better stratify patients and predict responses to HER2-targeted therapies currently available or in development. This capability may inform more tailored treatment strategies, ultimately improving patient outcomes in mCRC and potentially other HER2-amplified cancers.

"This study underscores the potential of AI technology to redefine how we evaluate biomarkers and predict treatment responses," said Dr. Takayuki Yoshino of the National Cancer Center Hospital East, principal investigator of the research. "The ability to more precisely stratify patients will lead to more personalized treatment options, improving outcomes for patients with HER2-positive metastatic colorectal cancer."

"The findings from this study demonstrate how Lunit’s AI-powered solutions, Lunit SCOPE HER2 and Lunit SCOPE IO, can provide clinicians with actionable insights to refine treatment strategies," said Brandon Suh, CEO of Lunit. "Our continued collaboration with NCCHE showcases the transformative potential of AI in precision oncology."