On January 23, 2025 Parabilis Medicines (formerly Fog Pharmaceuticals), a clinical-stage biopharmaceutical company dedicated to creating extraordinary medicines for people living with cancer, reported the presentation of a trial-in-progress poster on the Company’s first-in-human clinical trial evaluating FOG-001, the first and only direct inhibitor of β-cateninTCF4, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium taking place in San Francisco from January 23-25, 2025 (Press release, Parabilis Medicines, JAN 23, 2025, View Source [SID1234649861]).

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FOG-001 is being evaluated in a Phase 1/2 clinical trial (NCT05919264). The multicenter, open-label, non-randomized trial aims to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of FOG-001 in patients with microsatellite stable colorectal cancer (MSS CRC) and other solid tumors with Wnt pathway activating mutations (WPAM+). The trial plans to enroll patients in multiple third-line MSS CRC cohorts as both a monotherapy and in combination with FOLFOX+bevacizumab, anti-PD-1/PD-L1, or trifluridine/tipiracil+bevacizumab.

At the 2025 J.P. Morgan Healthcare Conference, Parabilis provided an update on the trial’s progress. The Company disclosed that more than 60 patients with locally advanced or metastatic solid tumors have been dosed with FOG-001 to date, and that early clinical data demonstrate monotherapy antitumor activity and in-tumor target engagement. Preliminary Phase 1/2 data are expected to be shared publicly in 2025.

Full details of the poster are as follows:

Title: "A Phase 1/2 study of FOG-001, a first-in-class direct β-catenin:TCF inhibitor, in patients with colorectal cancer, hepatocellular carcinoma, and other locally advanced or metastatic solid tumors"
Abstract Number: TPS322
Presentation Date and Time: January 25, 2025, 7:00-7:55 a.m. PST
Session Information: Trials in Progress Poster Session C
Location: Level 1, West Hall, Moscone West

About FOG-001
FOG-001 is an investigational first-in-class competitive inhibitor of β-catenin interactions with the T-cell factor (TCF) family of transcription factors, and is currently in clinical development. By directly targeting the β-cateninTCF4 protein-protein interaction, FOG-001 is intended to block the Wnt signaling pathway irrespective of the various APC and beta-catenin mutations that typically drive disease.

FOG-001 combines key features that distinguish it from previously reported Wnt/β-catenin pathway modulators: FOG-001 acts inside the cell where it binds directly to the key oncogenic driver β-catenin; and FOG-001 blocks the Wnt pathway at the most downstream node, disrupting the interaction between β-catenin and the transcription factor TCF, thereby abrogating the signal transmission by which Wnt pathway mutations are believed to drive oncogenesis. FOG-001 is currently being evaluated in a first-in-human Phase 1/2 clinical trial in patients with locally advanced or metastatic solid tumors.

On January 23, 2025 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported the company and its research collaborators will present data showcasing the benefits of Guardant’s precision oncology tools across cancer screening, recurrence monitoring, treatment selection and therapy development at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI) in San Francisco, January 23-25, 2025 (Press release, Guardant Health, JAN 23, 2025, View Source [SID1234649860]).

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Key focus areas in Guardant’s co-authored abstracts and collaborator presentations utilizing Guardant products include the impact of mutations on treatment response in colorectal cancer and biliary tract cancers, and additional support for the benefits of blood-based screening in colorectal, gastric and esophageal cancers. A rapid oral presentation will feature data from the phase II NEO trial highlighting Guardant Reveal as a decision tool to support organ preservation in patients with node-negative rectal cancer undergoing neoadjuvant chemotherapy, excision and observation.

"Data increasingly supports the value of precision oncology tools, and specifically liquid biopsy, in detecting GI cancers, informing treatment selection, and monitoring for recurrence and therapy response," said Craig Eagle, MD, Guardant Health chief medical officer. "Findings presented at ASCO (Free ASCO Whitepaper) GI demonstrate the advancements being made by Guardant Health and our partners in these areas and show the potential for these tools to provide even more personalized cancer care, leading to better patient outcomes."

Guardant Health ASCO (Free ASCO Whitepaper) GI 2025 Co-Authored Posters and Presentations

Time and Location

Title

Abstract and

Presentation Type

Guardant Reveal

January 25, 2025

9:15 – 10:00 am PST

Level 2, Ballroom

Tumour-free ctDNA detection as a decision tool to support organ preservation in node-negative rectal cancer undergoing neoadjuvant chemotherapy, excision, and observation in the phase II NEO trial (CCTG CO.28)

Rapid Oral Abstract

Session C

Abstract #20

Guardant360

January 25, 2025

7:00 – 7:55 am PST

Level 1, West Hall

Retrospective study evaluating the genomic landscape of anal squamous cell carcinoma using liquid biopsy

Poster Session C

Abstract #8

Landscape of metastatic colorectal cancer (CRC) using comprehensive circulating tumor DNA (ctDNA) next-generation sequencing (NGS) in India: Expanding beyond RAS and RAF

Poster Session C

Abstract #49

GuardantINFORM

January 24, 2025

11:30 am – 1:00 pm PST

Level 1, West Hall

Real-world survival differences in advanced biliary tract cancer patients with ctDNA detected IDH1 mutations and FGFR2 fusions receiving first-line gemcitabine-cisplatin with and without immunotherapy

Poster Session B

Abstract #548

ShieldTM

January 25, 2025

7:00 – 7:55 am PST

Level 1, West Hall

Cost-effectiveness of blood-based colorectal cancer screening: A simulation model incorporating real-world longitudinal adherence

Poster Session C

Abstract #93

A method for classifying colorectal cancer and gastric/esophageal cancer using blood-based testing

Poster Session C

Abstract #52

The full abstracts for Guardant Health and a list of all abstracts being presented at ASCO (Free ASCO Whitepaper) GI 2025 can be found on the ASCO (Free ASCO Whitepaper) website.

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.