On May 24, 2024 Tyligand Bioscience, a clinical-stage biotechnology company focused on the discovery and development of innovative cancer therapies, reported that the first patient had been dosed in the Phase 1/2 trial of TSN1611 for the treatment of KRAS G12D mutant solid tumors in the United States (Press release, Tyligand Bioscience, MAY 24, 2024, View Source [SID1234643698]). The program has been cleared for IND by U.S. FDA and China NMPA in Feb and April 2024, respectively.

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TSN1611 is a highly selective and orally bioavailable small molecule targeting the G12D mutant of KRAS oncogene, with excellent enzymatic and cellular activities. It effectively engages both the ON-state (GTP-bound) and OFF-state (GDP-bound) of KRAS G12D. TSN1611 has demonstrated superior in vivo anti-tumor activity with a durable response across multiple animal models. TSN1611 features favorable physicochemical properties, oral pharmacokinetic profiles, and notable brain penetration potential to address a large unmet medical need.

The ongoing first-in-human, multi-center clinical trial (NCT06385925) is designed to assess the safety, tolerability, pharmacokinetic profile, and preliminary anti-tumor activity in patients with advanced solid tumors harboring the KRAS G12D mutation. Patient recruitment is currently underway in the United States, with plans to initiate in China in the coming months.

"Preclinical profile indicated the potential of TSN1611 as a best-in-class molecule for treating cancers driven by KRAS G12D," said Dr. Tony Zhang, PhD., CEO of Tyligand Bioscience, "We are proud of our teams for the creativity, quality and speed in the discovery and early development efforts, and grateful for the support from our partners and investors in advancing TSN1611 one step closer toward the patients in need."

On May 24, 2024 STORM Therapeutics Ltd. (STORM), the clinical stage company pioneering cellular reprogramming through RNA modifications to treat disease, reported that it will be presenting interim clinical data on its first-in-class lead product, STC-15 at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place in Chicago, US from May 31 to June 4, 2024 (Press release, STORM Therapeutics, MAY 24, 2024, View Source [SID1234643697]).

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The poster presentation, entitled ‘Phase 1 Dose Escalation and Cohort Expansion Study Evaluating Safety, PK, PD and Clinical Activity of STC-15, a METTL3 Inhibitor, in Patients with Advanced Malignancies’, describes findings from STORM’s ongoing dose escalation and expansion Phase 1 clinical study to evaluate STC-15, an oral and highly selective small molecule inhibitor of METTL3, in advanced cancer patients. These interim results will focus on safety, pharmacokinetics, target modulation and tumor assessments to support future clinical studies. STC-15 is the first molecule specifically targeting an RNA methyltransferase enzyme to enter clinical development.

Preclinical data has demonstrated that METTL3 inhibition stimulates immune cells and activates interferon pathways, leading to the destruction of tumor cells. The poster presentation will detail the study design, patient demographics, safety data, pharmacokinetics, METTL3 target engagement, mechanistic biomarker data, and assessments of clinical activity.

Details of the poster presentation are as follow:

Poster Title: Phase 1 dose escalation and cohort expansion study evaluating safety, PK, PD and clinical activity of STC-15, a METTL3 inhibitor, in patients with advanced malignancies
Presenter: Justin Moser at HonorHealth Research Institute
Authors: Justin Moser[1], Kyriakos Papadopoulos[2], Jordi Rodon Ahnert[3], Yaara Ofir-Rosenfeld[4], Josefin-Beate Holz[4]
Organizations: [1]HonorHealth Research Institute, [2]START San Antonio, [3]The University of Texas MD Anderson Cancer Center, [4]Storm Therapeutics Ltd
Poster Session: Developmental Therapeutics—Immunotherapy
Session Date and Time: Saturday June 1, 2024, 9:00 AM – 12:00 PM CDT
Poster Board Number: 65
Abstract Presentation Number: 2586

The Abstract is available on the ASCO (Free ASCO Whitepaper) online itinerary planner here, and on the STORM website here.

On May 24, 2024 Shanghai Juncell Therapeutics Co., Ltd. (Juncell Therapeutics), a clinical-stage biotech developing innovative Tumor-Infiltrating Lymphocyte (TIL) therapies for cancers, reported latest clinical research results on GC203 (a novel non-viral vector gene-modified TIL therapy engineered with membrane-bound IL-7) (Press release, Juncell Therapeutics, MAY 24, 2024, View Source [SID1234643696]). These data will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place on May 31 – June 4, 2024.

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Researchers tested GC203 on patients diagnosed with recurrent ovarian cancer, without the combination of IL-2 administration or aggressive lymphodepletion. The objective of the study was to determine the safety and efficacy of this treatment. A total of 20 patients were enrolled between 09/2021 and 01/2024 in the open-label single-center trial, in which 18 patients were evaluable. The evaluable patients were with an ECOG PS of 1 (55.6%) or 2 (44.4%) and received a median of 5 previous systemic therapies (range: 2-11). 9 (50%) patients had 3 or more tumor lesions. The median target lesion size was 57 (range: 13-146) mm.

GC203 showed promising results in patients with recurrent or metastatic ovarian cancer. The safety profile was improved significantly compared with conventional TIL therapies, thanks to a low-intensity pretreatment and the elimination of IL-2 combination. Most of the Adverse Events (AEs) were grade 1 or grade 2 and could be alleviated or cured by symptomatic treatment. No grade 5 event occurred. By the cutoff date of 01/2024, the investigator-assessed Objective Response Rate (ORR) was 33.3% (95% CI: 16.3 – 56.3), including 11.1% Complete Response (CR). The Disease Control Rate (DCR) was 83.3% (95% CI, 60.8 – 94.2). And the 12-month Overall Survival (OS) rate was 68.8% (95% CI: 49.3 – 95.9). The median OS was not mature as data cut-off.

Presentation Details

Abstract Number: 5552

Abstract Title: A phase I single-arm, open-label trial of engineering tumor-infiltrating lymphocytes with membrane-bound lL-7 for recurrent ovarian cancer.

Session Type and Title: Poster Session – Gynecologic Oncology

Poster Presentation Time: 9:00 AM – 12:00 PM CDT, June 3, 2024

Presenter: Dr. Jing Guo, Shanghai Tenth People’s Hospital

The abstract is available on the ASCO (Free ASCO Whitepaper) website.

About Ovarian Cancer

Ovarian cancer has the highest mortality rate among gynecologic cancers. 70% of patients are diagnosed at an advanced stage. 70% of patients with advanced ovarian cancer have a survival time of less than five years. More than 200,000 people worldwide die from ovarian cancer each year, indicating a significant unmet clinical need. The primary treatment for advanced ovarian cancer is platinum-based chemotherapy. Ovarian cancer is insensitive to immunotherapy, with an ORR of less than 10%. Effective treatment options are limited.

About GC203

GC203 is a novel non-viral vector gene-modified TIL therapy developed leveraging Juncell Therapeutics’ proprietary DeepTIL cell expansion platform and NovaGMP gene modification platform. DeepTIL enables TILs to be potent enough that no IL-2 combination will be required after infusion, and the intensity of pretreatment could be lower. NovaGMP modifies T cells with a high efficiency comparable with the Lentiviral vector in an economic way. GC203 is engineered with self-associating membrane-bound interleukin-7, which can maintain the stemness of memory T cells, activate internal immune cells and avoid systemic toxicities.

On May 24, 2024 Lunit (KRX:328130.KQ), a leading provider of AI-powered solutions for cancer diagnostics and therapeutics, reported the presentation of seven studies at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2024 Annual Meeting in Chicago, from May 31 to June 4 (Press release, Lunit, MAY 24, 2024, View Source [SID1234643695]). Lunit will present detailed findings on several innovative studies, including the identification of HER2 ultra-low expression in breast cancer using AI-based quantification, and a deep learning-based model integrating chest CT and histopathology analysis for predicting immunotherapy response in non-small cell lung cancer (NSCLC).

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In a poster presentation, Lunit’s AI-powered HER2 analyzer, Lunit SCOPE HER2, demonstrated the ability to identify HER2 ultra-low expression and differentiate it from true HER2-negative cases in breast cancer patients using continuous subcellular quantification from HER2 immunohistochemistry (IHC) images.

According to findings presented at ASCO (Free ASCO Whitepaper) 2022, HER2-targeted antibody-drug conjugates (ADCs) can effectively target tumor cells even in HER2-low breast cancers. This highlights the importance of accurately identifying HER2-low and HER2 ultra-low expression in breast cancer, especially for patients previously classified as HER2-negative. In response, Lunit developed an AI-based whole-slide image (WSI) analyzer for IHC-stained slides to differentiate between true HER2-negative and HER2 ultra-low cases. The AI model evaluated over 67 million tumor cells and 119 million non-tumor cells from 401 WSIs, identifying a significant proportion of HER2 ultra-low cases among pathologist-assessed HER2 score 0 cases. This AI-powered analysis could expand and refine treatment options for patients with HER2-targeted therapies, as demonstrated by the 23.6% of HER2 score 0 cases identified as HER2 ultra-low by AI, and the 51.9% of HER2 score 1+ cases classified as HER2 low by AI, comparable to the 52.3% objective response rate to a HER2-targeted ADC observed in another clinical trial.

In another study, Lunit developed and validated an AI model that analyzes patients’ chest CT images alone and in combination with pathology images to predict Immune Checkpoint Inhibitor (ICI) response in NSCLC patients. Lunit’s deep learning-based chest CT prediction model, developed using data from 1,876 NSCLC patients treated with ICIs, predicted treatment response based on pre-treatment chest CT scans, along with PD-L1 status and immune phenotype. The model demonstrated significant predictive power as an independent biomarker. Patients predicted as responders by the AI model showed significantly longer median time to the next treatment (TTNT; 7 months vs. 2.5 months) and a longer overall survival (OS; 16.5 months vs. 7.6 months) compared to patients predicted as non-responders. Combining the AI CT model with histopathologic biomarkers such as PD-L1 expression and tumor-infiltrating lymphocytes (TILs) further enhanced prediction accuracy, highlighting the complementary strengths of imaging and pathology data in improving predictive models for ICI response.

A collaborative study with Stanford University School of Medicine examined the association of immune phenotypes with outcomes after immunotherapy in metastatic melanoma, highlighting the heterogeneity of immune phenotypes across melanoma subtypes.

Another study with Northwestern University utilized AI-powered analysis of tertiary lymphoid structures (TLS) in H&E whole-slide images to predict immunotherapy response in NSCLC patients. This demonstrated AI’s potential in identifying predictive biomarkers for survival outcomes.

"At ASCO (Free ASCO Whitepaper) 2024, Lunit proudly presents seven groundbreaking studies that illustrate our pioneering role in AI-driven precision oncology," said Brandon Suh, CEO of Lunit. "From HER2 quantification to predictive models for immunotherapy response, our work is transforming oncology by making cancer treatment not just personalized but predictive, ensuring the best possible outcomes for patients worldwide."

In addition to the studies above, Lunit will present three more studies at this year’s ASCO (Free ASCO Whitepaper), demonstrating the diverse capabilities of the Lunit SCOPE suite. The studies include comprehensive histopathomic prediction models for early breast cancer, and hypothetical test-and-control group generation for treatment selection in TPS-high NSCLC.

Visit Lunit at booth IH22 to discover how the Lunit SCOPE suite is revolutionizing oncology research and clinical practice.

Presentations at ASCO (Free ASCO Whitepaper) 2024 featuring Lunit SCOPE include:

"Identification of HER2 ultra-low based on an artificial intelligence (AI)-powered HER2 subcellular quantification from HER2 immunohistochemistry images" (1115, Poster Board #93)
"Deep learning–based chest CT model to predict treatment response to immune checkpoint inhibitors in non-small cell lung cancer independently and additively to histopathological biomarkers" (8536, Poster Board #400)
"Artificial intelligence (AI) –powered H&E whole-slide image (WSI) analysis to predict recurrence in hormone receptor positive (HR+) early breast cancer (EBC)" (571, Poster Board #163)
"Immune phenotype profiling based on anatomic origin of melanoma and impact on clinical outcomes of immune checkpoint inhibitor treatment" (9569, Poster Board #353)
"Artificial intelligence (AI) -powered H&E whole-slide image (WSI) analysis of tertiary lymphoid structure (TLS) to predict response to immunotherapy in non-small cell lung cancer (NSCLC)" (3135, Poster Board #280)
"Updated safety, efficacy, pharmacokinetics, and biomarkers from the phase 1 study of IMC-002, a novel anti-CD47 monoclonal antibody, in patients with advanced solid tumors" (2642, Poster Board #121)
"Relationship between immune phenotype and treatment selection of Chemo-IO vs. IO-only in TPS-high NSCLC using hypothetical test-and-control group generation based on survival data extracted from phase III trials" (e13569)

On May 24, 2024 Rakuten Medical, Inc., a global biotechnology company developing and commercializing precision, cell-targeting photoimmunotherapy based on its proprietary Alluminox platform, reported the updated safety and efficacy findings from an interim evaluation of an open-label Phase 1b/2 study (ASP-1929-181/ClinicalTrials.gov Identifier: NCT04305795) of photoimmunotherapy using ASP-1929 in combination with anti-PD-1 for recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) (Press release, Rakuten Medical, MAY 24, 2024, View Source [SID1234643694]). The data will be presented in a poster at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO 2024) on June 2, 2024.

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The updated interim evaluation (data cut-off: August 31, 2023) of 19 enrolled patients in ASP-1929-181 study suggests that the novel treatment approach of ASP-1929 photoimmunotherapy in combination with anti-PD-1 showed promising early results in patients with locoregional and/or metastatic HNSCC. Median overall survival (OS) was not reached at data cut-off, with an estimated survival rate of 52.4% at 24 months, and an objective response rate (ORR) of 35.3%. Adverse events were generally manageable, and the combination therapy was generally tolerated with an absence of synergistic serious adverse events.

The encouraging early efficacy and safety outcomes warrant additional clinical studies to substantiate and reinforce these interim findings. Rakuten Medical recently completed a Type B End-of-Phase 2 (EOP2) meeting with the U.S. Food and Drug Administration (FDA) for the combination of ASP-1929 photoimmunotherapy and anti-PD-1 in the first-line recurrent HNSCC setting and discussed the key details for a multi-regional registrational study. Based on these results, Rakuten Medical plans to initiate this global phase 3 clinical trial with a primary endpoint of OS in the second half of 2024.

Disclaimer: These interim findings may change upon completion of follow-up and final data analysis.

Key findings

[Efficacy]

Clinically meaningful activity was observed
Median Overall Survival (OS) was not reached, with an estimated survival rate of 52.4% (95% CI: 25.9-73.4) at 24 months
The objective response rate (ORR) was 35.3% (6 patients, 95% CI: 14.2-61.7), which included 4 complete responses (CR) (23.5%, 95% CI: 6.8-49.9) and 2 partial responses (PR) (11.8%, 95% CI: 1.5-36.4)
Median time to response of 1.4 months
Median progression-free survival (PFS) was at 2.9 months (95% CI 1.4-14.6)
[Safety]

Adverse events were manageable and generally tolerated
No fatal serious adverse events (SAEs)
Two Grade 4 SAEs: laryngeal edema related to photoimmunotherapy and tumor hemorrhage unrelated to study treatment, both of which resolved
No synergistic SAEs due to ASP-1929 and anti-PD-1
Upcoming Rakuten Medical’s Poster Presentation at ASCO (Free ASCO Whitepaper)

Abstract Title: Recent safety and efficacy findings from a phase 1b/2 open-label combination study of ASP-1929 photoimmunotherapy with anti-PD-1 therapy in EGFR-expressing advanced head and neck squamous cell carcinoma (HNSCC)
Abstract Number: 6083
Abstract Link: View Source
Session Name: Poster Session – Head and Neck Cancer
Session Date: Sunday, June 2, 2024
Session Time: 9:00 a.m. – 12:00 p.m., CDT
First Author: David M. Cognetti, Department of Otolaryngology – Head and Neck Surgery, Thomas Jefferson University, US
Location: Exhibit Hall A, Poster Board #399