On May 22, 2025 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on developing innovative CAR T-cell therapies, reported that an abstract of the research results of the confirmatory Phase II clinical trial of satricabtagene autoleucel ("satri-cel", CT041) (an autologous CAR T-cell product candidate against protein Claudin18.2) for advanced gastric/gastroesophageal junction cancer (G/GEJC) in China (CT041-ST-01, NCT04581473) is available on the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") website (Press release, Carsgen Therapeutics, MAY 22, 2025, View Source [SID1234653329]).

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Title

Claudin18.2-specific CAR T cells (Satri-cel) versus treatment of physician’s choice (TPC) for previously treated advanced gastric or gastroesophageal junction cancer (G/GEJC): Primary results from a randomized, open-label, phase II trial (CT041-ST-01)

Abstract Number

4003

Session Type and Title

Oral Abstract Session – Gastrointestinal Cancer— Gastroesophageal, Pancreatic, and Hepatobiliary

Session Date and Time

May 31, 2025, 3:00–6:00 PM CDT

This open-label, multicenter, randomized controlled trial (RCT) was conducted in China to compare the efficacy and safety of satri-cel versus standard of care (SOC) in CLDN18.2 positive, advanced G/GEJC patients with failure to at least 2 prior lines of treatment. The primary endpoint was PFS assessed by the Independent Review Committee (IRC). Key secondary endpoint was OS. Data cutoff date was Oct 18, 2024.

Patients were randomized (2:1) to satri-cel arm or TPC arm. For satri-cel arm, satri-cel dose of 250×106 cells were infused up to 3 times. For TPC arm, one of the standard of care (SOC) drugs (apatinib, paclitaxel, docetaxel, irinotecan or nivolumab) was given per physician’s decision. Those who experienced disease progression or drug intolerance in TPC arm could receive subsequent satri-cel, if eligible.

From Mar 29, 2022 to Aug 16, 2024, a total of 156 patients were randomized to satri-cel arm (n = 104) or TPC arm (n = 52). Twenty patients in TPC arm received subsequent satri-cel. Median number of prior systemic therapies was 2 in both arms, and 26.9% vs 19.2% had received ≥3 lines. 71.2% vs 65.4% were Lauren diffuse/mixed type. 69.2% vs 59.6% had peritoneal metastasis.

In ITT population (i.e., all randomized patients), satri-cel arm showed significant improvement in mPFS by IRC (3.25m vs 1.77m; HR 0.366, 95% CI:0.241, 0.557; p < 0.0001) meeting the primary endpoint with a 63% reduction in risk of disease progression or death. Even with 15.4% (n=16) patients in satri-cel arm failing to receive infusion and nearly 40% (n=20) patients in TPC arm receiving subsequent satri-cel, satri-cel arm still demonstrated a clear trend toward OS benefit (mOS 7.92m vs 5.49m; HR 0.693, 95% CI: 0.457, 1.051; one-sided p = 0.0416) , showing over 30% reduction in mortality risk.

More importantly, in mITT population (i.e. patients who were actually treated), 136 patients received study drug (satri-cel 88 patients vs TPC 48 patients), mPFS by IRC was 4.37m vs 1.84m, HR 0.304 (95% CI: 0.195, 0.474), representing a 70% reduction in risk of disease progression or death. The mOS was 8.61m vs 5.49m, HR 0.601 (95%CI: 0.385, 0.939), corresponding to 40% reduction in mortality risk. These results demonstrate that satri-cel treatment benefits were pronounced in patients who actually received CAR-T infusion.

Of particular note, 20 TPC patients with subsequent satri-cel infusion achieved an mOS of 9.20 months. When analyzing all 108 patients who received satri-cel infusion (88 patients in satri-cel arm and 20 patients in TPC arm), the mOS reached 9.17 months, while the mOS of 28 patients in TPC arm who did not receive satri-cel treatment was only 3.98 months (HR 0.288; 95% CI: 0.169-0.492). These findings provide further evidence that satri-cel infusion can deliver substantial survival benefits for patients.

Furthermore, satri-cel demonstrated a favorable overall safety profile. Only 4 cases of Grade 3 cytokine release syndrome (CRS) were reported, and no Grade 4-5 CRS events were observed. No immune effector cell-associated neurotoxicity syndrome (ICANS) was reported.

This is the first confirmatory RCT of CAR-T therapy in solid tumors. Satri-cel demonstrated significant PFS improvement and a clinically meaningful OS benefit with a manageable safety profile in CLDN18.2 positive G/GEJC patients with failure to at least 2 prior lines of treatment, compared to standard therapy. These results support satri-cel as a potential new SOC for advanced G/GEJC.

About Satri-cel

Satri-cel is an autologous CAR T-cell product candidate against the protein Claudin18.2 that has the potential to be the first-in-class globally. Satri-cel targets the treatment of Claudin18.2 positive solid tumors with a primary focus on G/GEJA and pancreatic cancer (PC). Initiated trials include investigator-initiated trials (CT041-CG4006, NCT03874897), a confirmatory Phase II clinical trial for advanced G/GEJA in China (CT041-ST-01, NCT04581473), a Phase I clinical trial for PC adjuvant therapy in China (CT041-ST-05, NCT05911217), an investigator-initiated trial for satri-cel be used as consolidation treatment following adjuvant therapy in patients with resected G/GEJA (CT041-CG4010, NCT06857786), and a Phase 1b/2 clinical trial for advanced gastric or pancreatic adenocarcinoma in North America (CT041-ST-02, NCT04404595). Satri-cel has been granted Breakthrough Therapy Designation by the Center for Drug Evaluation of China’s National Medical Products Administration for the treatment of Claudin18.2-positive advanced G/GEJA in patients who have failed at least two prior lines of therapy in March 2025. Satri-cel was granted Regenerative Medicine Advanced Therapy designation by U.S. FDA for the treatment of advanced G/GEJA with Claudin18.2-positive tumors in January 2022. Satri-cel received Orphan Drug designation from the U.S. FDA in September 2020 for the treatment of G/GEJA.

On May 22, 2025 Rakuten Medical, Inc., a global biotechnology company developing and commercializing Alluminox platform-based photoimmunotherapy, reported that it will present a Trial in Progress poster at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which will take place May 30 – June 3, 2025, in Chicago, Illinois (Press release, Rakuten Medical, MAY 22, 2025, View Source [SID1234653328]).

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The poster will feature Rakuten Medical’s ongoing global Phase 3 clinical trial evaluating ASP-1929 photoimmunotherapy in combination with pembrolizumab (anti-PD-1) as a first-line therapy for patients with recurrent head and neck squamous cell carcinoma (HNSCC) (Protocol number: ASP-1929-381 / Acronym: ECLIPSE / ClinicalTrials.gov Identifier: NCT06699212). The poster will also highlight interim findings from the completed Phase 1b/2 study (ASP-1929-181 / ClinicalTrials.gov Identifier: NCT04305795) which evaluated ASP-1929 photoimmunotherapy in combination with anti-PD-1 in recurrent or metastatic HNSCC.

"We are honored that our Trial in Progress poster has been accepted for presentation at ASCO (Free ASCO Whitepaper) 2025," said Anastasios Maniakas, MD, PhD, Assistant Professor in the Department of Head and Neck Surgery and an investigator of the ASP-1929-381 study at The University of Texas MD Anderson Cancer Center. "This Phase 3 study represents a significant step forward in evaluating the potential synergistic efficacy of ASP-1929 photoimmunotherapy and pembrolizumab as a first-line treatment for patients with recurrent HNSCC. We look forward to sharing our progress with the global oncology community and advancing innovative approaches for the treatment of patients facing this challenging disease."

Rakuten Medical is also pleased to announce that it has recently initiated patient enrollment in Taiwan as part of its global expansion of the Phase 3 ASP-1929-381 study. Currently, over 10 clinical sites across the United States and Taiwan are actively enrolling patients. Additional sites are expected to be activated in both regions, with patient enrollment in Japan anticipated to begin shortly.

"We are pleased to be part of this global Phase 3 study and to contribute to the development of an innovative treatment approach like photoimmunotherapy," said Kai-Ping Chang, MD, PhD, Professor of the Department of Otolaryngology – Head & Neck Surgery and Principal Investigator of the ASP-1929-381 study at Chang Gung Memorial Hospital in Taiwan. "Head and neck cancer ranks third in male cancer incidence and fourth in male cancer mortality in Taiwan1. Local recurrence or metastasis is one of the leading causes of death in these patients2, and nearly half of those with recurrent or metastatic disease survive for less than one year3. By participating in this trial, we hope to help advance new therapeutic options that may prolong overall survival of patients with recurrent HNSCC, both in Taiwan and around the world."

ASCO attendees are invited to visit Rakuten Medical at booth #33110 to learn more about the ASP-1929-381 study and the company’s broader Alluminox platform.

Rakuten Medical’s Trial in Progress Poster Overview

Abstract Title: A phase 3 randomized study of ASP-1929 photoimmunotherapy in combination with pembrolizumab versus standard of care in locoregional recurrent head and neck squamous cell carcinoma (HNSCC)
Abstract Number: TPS6122
Abstract Link: View Source
Session: Poster Session – Head and Neck Cancer
Date: Monday, June 2, 2025
Time: 9:00 a.m. – 12:00 p.m., CDT
First Author: Anastasios Maniakas, The University of Texas MD Anderson Cancer Center, TX, the U.S.
Location: Exhibit Hall A, Poster Board # 523b
Rakuten Medical Exhibit Booth

Location: Exhibit Hall A, Booth #33110
Exhibit Date: Saturday – Monday, May 31 – June 2, 2025
About ASP-1929-381 Study
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. 412 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).

On May 22, 2025 GNTbm (stock code: 7427, Taiwan) reported the preclinical data on GNTbm-38, an novel epigenetic immune activator for cancer immunotherapy. GNTbm-38 was presented as posters at the 2025 American Association of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which is held in Chicago, USA, from May 30 to Jun 04, 2025 (Press release, GNT Biotech & Medicals, MAY 22, 2025, View Source;medicals-corporation-gntbm-presented-preclinical-data-on-gntnm-38-an-novel-epigenetic-immune-activator-at-the-2025-asco-annual-meeting-302461449.html [SID1234653327]).

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Abstract: 2574

Title: Preclinical development of GNTbm-38, a novel class I histone deacetylase inhibitor, while combined with anti-VEGFR TKI or anti-PD-1 Ab: Assessment of immune activation and immune memory in cancer immunotherapy.

Session Date/Time: 6/2/2025, 1:30 PM-4:30 PM CT

Poster Board Number: 221

At present, there is no ICI-based drug combination for the treatment of advanced MSS colorectal cancer, which is a cold tumor. Studies have shown that epigenetic regulators such as class I HDAC inhibitors are an emerging and important drug component for combination therapy that can greatly increase the anti-cancer benefits of cancer immunotherapy. Therefore, rational drug combinations, containing class I HDACi, may provide opportunities in cancer immunotherapy.

GNTbm-38 is a new drug candidate independently developed by GNTbm. GNTbm-38 acts as a TME reprogramming regulator in immunotherapy. When combined with TKI, GNTbm-38 significantly improved tumor response rate and survival rate through synergistic effect by normalizing tumor vessels, increasing tumor antigen presentation, increasing activated CD8+ T cell infiltration into tumors, inducing memory T cell persistence, and inhibiting mobilization of immunosuppressive cells into tumors. On the other hand, treatment with GNTbm-38 plus anti-PD-1 antibody in the CT-26 model showed greatly improved tumor response rate and survival rate with a strong synergistic effect. Furthermore, in B-hPD-1/hPD-L1 mice (humanized model) subcutaneously injected with B-hPD-L1 CT-26 cells, treatment of pembrolizumab and GNTbm-38 resulted in a 46.5% inhibition on tumor growth. Therefore, our data provided a strong rationale to explore the combination of GNTbm-38 with anti-VEGF TKI with or without ICI. From these data GNTm-38 has been shown to display powerful induction of immune activation and immune memory in combination therapy with TKI/ICI against colon CT-26 cold tumor. Based on the in vitro, in vivo and preclinical studies, these data show that GNTbm-38 exhibits markedly superior pharmacokinetics, tolerability, and efficacy in animal models. It is expected to complete the US IND application by the end of 2025 and enter the clinical study.

About GNTbm-38

GNTbm-38 is a new chemical entity with potential as a pivotal drug component of a new generation of cancer immunotherapy independently developed by GNTbm. It is a drug candidate selected by an immuno-competent tumor-bearing animal testing platform, and has undergone many preclinical research studies to confirm that it has very outstanding anti-cancer activity in tumor microenvironment. GNTbm-38 is an oral drug with dual effects of epigenetic regulation of gene expression and immune activation, which is unique when compared to the mechanism of other epigenetic drugs. GNTbm-38 can remodel the tumor microenvironment (TME) through a unique epigenetic regulatory mechanism, including the cell composition and gene expression that affect the TME, so that "cold tumors" can be transformed into "hot tumors", which can attract CTL to infiltrate into the TME, and at the same time, it can also reduce the attraction of immunosuppressive cells (such as : TAM, Treg, and MDSCs) into the TME, so as to achieve the remodeling of the TME, which is more conducive to obtaining the therapeutic benefits of cancer immunotherapy. GNTbm-38 monotherapy can be used in the treatment of hematological tumors, and GNTbm-38 can also be combined with a unique multi-kinase inhibitor or immune checkpoint inhibitor for treatment of a variety of solid tumors, mainly through a unique anti-cancer immune-regulating mechanism to achieve anti-cancer treatment goals.

On May 22, 2025 PRISM BioLab, Co. Ltd. ("PRISM"), a leading discovery and development biotechnology company designing small molecule inhibitors of protein-protein interaction (PPI) targets, reported that the analysis of a combination study of E7386(*1), created through collaboration research with Eisai Co., Ltd. ("Eisai"), and Lenvatinib mesylate ("lenvatinib") (*2) will be presented by Eisai at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Congress 2025, held in Chicago, USA from May 30 to June 3, 2025 (Press release, Eisai, MAY 22, 2025, View Source [SID1234653326]). The abstract of the study has been released today.

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To determine the optimal dose of E7386 in combination with Lenvatinib in the open-label Phase Ib study (NCT04008797(*3)), expansion cohort of advanced endometrial cancer patients progressed following platinum-based chemotherapy and anti-PD-(L)1 immunotherapy have been implemented by Eisai and the enrollment of 30 patients was completed. By data cutoff (Oct 22, 2024), with 9 patients remaining on treatment, 30% (9 patients) showed the confirmed response (decrease of tumor size > 30%) for an overall response rate of 30.0%. Furthermore, among patients without prior Lenvatinib treatment, the overall response rate was 42.9%.

Completing the enrollment of dose expansion cohort (n=30), the results confirmed promising preliminary antitumor activity of E7386 + Lenvatinib with a manageable safety profile. For the subsequent dose-optimization part for E7386 + LEN in advanced endometrial cancer, enrollment of patients had been initiated (NCT04008797).

(*1) E7386

E7386 is an orally available small molecule CBP/ β-catenin inhibitor that inhibits protein-protein interactions between the transcription factor CBP and β-catenin, and regulates the Wnt signaling. E7386 achieved clinical POC (Proof of concept) in October 2021 and following clinical studies are ongoing including phase I for solid tumors as monotherapy, Phase Ib for solid tumors in combination with tyrosine kinase inhibitor Lenvatinib, Phase Ib/II for solid tumors in combination with pembrolizumab, the anti-PD-1 antibody from Merck & Co., Inc., Rahway, NJ, USA.

(*2) Lenvatinib

Lenvatinib is a multi-kinase inhibitor, discovered by Eisai and being co-developed and co-commercialized under a collaboration agreement with Merck & Co., Inc., Rahway, NJ, USA, which inhibits vascular endothelial growth factor receptors (VEGFRs),VEGFR1, VEGR2, VEGFR3 and fibroblast growth factor receptors (FGFRs), FGFR1, FGFR2, FGFR3, FGFR4, and other receptor tyrosine kinases, PDGFR-alpha, KIT, RET. Lenvatinib have been approved for thyroid cancer, hepatocellular carcinoma, thymic caner and renal cell carcinoma (in combination with Everolimus or pembrolizumab, the anti-PD-1 antibody from Merck & Co., Inc., Rahway, NJ, USA.). Lenvatinib is also approved for endometrium cancer in combination with pembrolizumab

(*3) NCT04008797

NCT04008797 is an open-label Phase Ib study of E7386 in combination with other anticancer drug, Lenvatinib for the patients with solid tumors. The study has been implemented by Eisai in Japan, Korea, Taiwan region, US, and France determine the safety and the recommended phase 2 dose (RP2D) and also to see the pharmacokinetics and efficacy of E7386 + Lenvatinib. Enrolment of each cohort of hepatic, colon, endometrial cancers are ongoing.

On May 22, 2025 Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, reported that it will present two-year disease-free survival (DFS) data from all patients in the randomized Phase I part of the trial of its individualized neoantigen therapeutic cancer vaccine TG4050 (Press release, Transgene, MAY 22, 2025, View Source [SID1234653325]). The data will be shared during a rapid oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place in Chicago from May 30 to June 3, 2025.

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TG4050 is a viral vector-based immunotherapy based on Transgene’s myvac platform and powered by NEC’s cutting-edge AI capabilities designed to optimize antigen selection.
TG4050 is being evaluated in a randomized multicenter Phase I/II trial as a single agent in the adjuvant treatment of HPV-negative head and neck cancers (NCT04183166). Based on promising Phase I data, Transgene and partner NEC have advanced the joint development of TG4050 in this indication with a Phase II extension of the trial, which is currently enrolling patients.

Key data to be presented include:

Safety in locally advanced HPV-negative resectable head and neck squamous cell carcinoma (HNSCC),
Disease free survival after 2-year follow-up,
Updated immunogenicity data.
Prof. Le Tourneau, MD, PhD, Head of the Department of Drug Development and Innovation (D3i) at Institut Curie, and Principal Investigator commented: "It is a privilege to present these study data which are based on the highly promising myvac platform for individualized cancer vaccines. This oral presentation at ASCO (Free ASCO Whitepaper) offers an opportunity to highlight both the strength of the clinical data and the collaborative efforts of everyone involved in the trial."

Dr. Emmanuelle Dochy, MD, Chief Medical Officer of Transgene, added: "We are pleased to have our latest findings on TG4050 selected for presentation among so many high-quality submissions to ASCO (Free ASCO Whitepaper). This recognition reflects the dedication of our teams and the significance of our work in advancing medical science and patient care for those suffering from cancer. The Phase II part of our trial is currently enrolling patients internationally, as we continue to evaluate TG4050’s potential in this setting."

The rapid oral presentation will take place on June 1st at 1:30 p.m. CDT during ASCO (Free ASCO Whitepaper) 2025 and will also be available to view on Transgene’s website.

In addition, Transgene will present a poster at ASCO (Free ASCO Whitepaper) on TG4001, presenting randomized Phase II data in combination with avelumab in a cervical cancer subgroup. Following the previously reported topline results from this study in the overall patient population (see press release here), Transgene is currently evaluating potential partnership opportunities to determine the best path forward for the program.