On November 8, 2024 Lunit (KRX:328130.KQ), a leading provider of AI-powered solutions for cancer diagnostics and therapeutics, reported groundbreaking research findings demonstrating the potential of its AI to predict immunotherapy treatment outcomes in rare tumors (Press release, Lunit, NOV 8, 2024, View Source [SID1234648042]). Conducted in collaboration with The University of Texas MD Anderson Cancer Center, this study will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2024 Annual Meeting, held November 6-10 in Houston, Texas. Accepted as a Rapid Oral presentation, the study will be presented by Mohamed Derbala, M.D., a research scientist at MD Anderson. It has also been selected as one of the SITC (Free SITC Whitepaper) TOP 100 abstracts, underscoring its potential significance and impact in the field of immunotherapy.

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Immunotherapy, particularly immune checkpoint inhibitors like pembrolizumab, has emerged as a revolutionary treatment option for cancer patients. However, not all patients respond equally to this treatment, and predicting who will benefit most has been a significant challenge, especially in rare tumor types where treatment options and research data are limited.

Led by principal investigator Dr. Aung Naing, professor of Investigational Cancer Therapeutics at MD Anderson, the research utilized Lunit’s AI-powered whole-slide image analyzer, Lunit SCOPE IO, to assess tumor microenvironment characteristics in both pre-treatment and on-treatment biopsies from patients with rare tumors receiving pembrolizumab. The study analyzed over 500 slides across more than 10 different rare tumor types.

The findings indicate that Lunit SCOPE IO could effectively identify specific patterns in tumor samples that correlate with better treatment outcomes. The research showed that patients whose tumor samples displayed AI-detected changes in both intratumoral immune cell (intratumoral tumor-infiltrating lymphocyte; iTIL) presence and tumor content, were significantly more likely to have better treatment outcomes positively to immunotherapy treatment.

Key findings from the study include:

In certain tumor types, patients with higher pre-treatment iTIL density showed a 51% lower risk of disease progression or death (improved progression-free survival, PFS; HR: 0.49)
Patients who had greater iTIL density increase at on-treatment biopsy showed a 35% lower risk of disease progression or death (HR: 0.65) and a 41% lower risk of death (improved overall survival, OS; HR: 0.59)
Patients with greater tumor content decrease at on-treatment biopsy had a 49% lower risk of disease progression or death (HR: 0.51) and a 46% lower risk of death (HR: 0.54)
Most notably, patients who experienced both a greater iTIL density increase and tumor content decrease showed dramatically improved outcomes:
68% lower risk of disease progression or death
72% lower risk of death
"These findings highlight how our AI technology can provide deep insights into the unique and challenging tumor microenvironment seen in rare cancers, and represent a critical advancement in our understanding of rare tumor biology," said Brandon Suh, CEO of Lunit. "This study has demonstrated the value of Lunit SCOPE IO in an important clinical setting, showcasing its potential to personalize treatment for patients who have limited therapeutic options. We believe these advancements are a testament to the transformative impact AI can have on oncology and patient outcomes."

By expanding the capabilities of Lunit SCOPE IO, Lunit aims to continue partnering with leading cancer research institutions to deliver innovative and meaningful solutions for patients with limited treatment options, ultimately transforming cancer care.

For more details about the study and its findings, please visit Lunit’s booth #317 at the SITC (Free SITC Whitepaper) 2024 Annual Meeting.

Abstract #1207, "Artificial Intelligence-powered assessment of tumor microenvironment in pre-treatment and on-treatment biopsies informs treatment outcomes to pembrolizumab in patients with rare tumors." (Nov.9, 1:08 p.m., George R. Brown Convention Center – Level 3 – Grand Ballroom C)

On November 8, 2024 HUYABIO International reported it will present the final analysis of data from a phase 2 study evaluating HBI-8000 in combination with nivolumab (anti-PD1 therapy), a novel combination for the treatment of advanced and metastatic melanoma (Press release, HUYA Bioscience, NOV 8, 2024, View Source [SID1234648041]).

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The results will be presented by Study Chair, Dr. Nikhil Khushalani, Senior Member and Vice Chair, Department of Cutaneous Oncology from Moffitt Cancer Center, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2024 Annual Meeting on Saturday, November 9.

HBI-8000, an oral drug, when combined with nivolumab has shown encouraging efficacy signals in treating patients with advanced and metastatic melanoma. This innovative therapy has clinically meaningful advantages over traditional double immune checkpoint inhibitor combinations, offering patients an oral treatment in combination with nivolumab that has enhanced efficacy and reduced toxicities.

"The promising results from the HBI-8000 and nivolumab combination represent a significant advancement in treating advanced melanoma," said Dr. Mireille Gillings, President, CEO & Executive Chair at HUYABIO. "Coupling oral convenience with a reduction in immune-related toxicities will give clinicians new tools to improve patient outcomes. We are proud to contribute to this new era of immunotherapy that prioritizes both efficacy and patient well-being."

"We are pleased to share the final Phase 2 results of the HBI-8000 and nivolumab combination in patients with advanced melanoma at this year’s SITC (Free SITC Whitepaper) conference," said Dr Nikhil Khushalani. "The combination appears safe and effective in this Phase 2 study, which may show great promise in this patient population. HBI-8000 plus nivolumab could be an important addition to the armamentarium of oncologists treating this disease and is currently being investigated in a Phase 3 study."

Title: HBI-8000, a class I histone deacetylase (HDAC) inhibitor, in combination with nivolumab for treatment of anti-PD(L)1-naive advanced melanoma: final analysis of Study HBI-8000-302

Abstract Number: 620

Authors: Nikhil I. Khushalani1 (Presenter), Andrew Brohl1, Joseph Markowitz1, Heather Yeckes-Rodin2, Lori McCormick1, Charlie Liu3, Mireille Gillings3, Gloria Lee3, and Zeynep Eroglu1

1H. Lee Moffitt Cancer Center, Tampa FL, 2Hematology-Oncology Associates of the Treasure Coast, Port. St. Lucie, FL, 3HUYABIO International, San Diego, CA, USA

Oral Presentation Date and Time: Saturday, November 9th at 3:44 PM CST

Addressing the Unmet Need for Innovative Melanoma Therapies

The combination of HBI-8000 and nivolumab represents a significant advancement in melanoma treatment. As the first combination therapy that does not rely on dual immune checkpoint inhibitors, it presents a desirable option for community practices and specialty cancer centers, particularly in regions with limited technical support. This therapy can potentially expand combination therapy for melanoma containing nivolumab-backbone beyond established markets in the U.S. and EU, providing access to more patients worldwide.

About the HBI-8000 Phase 2 Trial

The trial was a Phase 1b/2 trial evaluating the combination of HBI 8000 with nivolumab (an anti-PD1 immune checkpoint inhibitor) in advanced melanoma, kidney cancer and non-small cell lung cancer. The recommended Phase 2 dose of HBI-8000 was determined to be 30mg orally twice weekly (BIW) combined with intravenous nivolumab administered at the manufacturer’s approved dosing schedule. Patients with metastatic melanoma not previously treated with anti-PD(L)-1 inhibitor, with measurable disease, ECOG performance status 0-1, and adequate hematologic and biochemical parameters were enrolled. Previously treated stable brain metastases not requiring steroids were permitted. Disease status was assessed by standard imaging using RECIST v1.1 every 8 weeks. Treatment was continued until disease progression, unacceptable toxicity or completion of 24 months of therapy.
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On November 8, 2024 Cue Biopharma, Inc. (Nasdaq: CUE), a clinical-stage biopharmaceutical company developing a novel class of therapeutic biologics to selectively engage and modulate disease-specific T cells for the treatment of cancer and autoimmune disease, reported updated data from its Phase 1 dose escalation and expansion trial evaluating its lead oncology asset from the Immuno-STAT CUE-100 series, CUE-101, in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) (Press release, Cue Biopharma, NOV 8, 2024, View Source [SID1234648040]). The data was presented in an oral session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 39th Annual Meeting (SITC 2024) being held in Houston, Texas and virtually November 6-10.

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In addition, on Saturday, November 9, 2024, the Company will present a poster with data from its Phase 1 trial evaluating monotherapy activity of its second clinical asset from the CUE-100 series, CUE-102, for the treatment of patients with late-stage Wilms Tumor 1 positive (WT1+) colorectal, gastric, ovarian and pancreatic cancers. Data showed substantial evidence of selective expansion of WT1-specific T cells, with anti-tumor activity and a favorable tolerability profile with no dose limiting toxicities (DLTs) observed.

"The therapeutic responses observed with CUE-101 and pembrolizumab are very promising. The combination has been well-tolerated and demonstrates durable clinical benefit," said Christine H. Chung, M.D., Department Chair, Head and Neck-Endocrine Oncology, Moffitt Cancer Center, and a principal investigator participating in the CUE-101 clinical trial. "The latest results highlight the potential of CUE-101 to improve response rates and quality of life for this patient population."

Key data highlights from the expansion portion of the trial evaluating CUE-101 at the recommended Phase 2 dose (RP2D) of 4mg/kg in combination with pembrolizumab in 1L HPV+ R/M HNSCC patients (data cutoff of September 11, 2024) include:

ORR of 46% and overall disease control rate (DCR) of 75% in patients with combined positive score (CPS) ≥1, compared to an ORR of 19% observed with pembrolizumab alone in the historical third-party KEYNOTE-048 trial. This includes one complete response (CR) and 10 partial responses (PR), in addition to seven durable stable diseases (DSD) of >12 weeks.
Survival metrics continue to mature: 12-month OS of 91.3% compared to 51% with pembrolizumab alone in the historical KEYNOTE-048 trial.
mOS of 21.8 months compared to 12.3 months in the historical KEYNOTE-048 trial.
ORR of 50% in patients with PD-L1 CPS 1-19.
Key data highlights from the CUE-101 expansion portion of the Phase 1b trial evaluating CUE-101 at the RP2D as monotherapy with 20 second line and beyond (2L+) patients (majority third line and beyond (3L+) (data cutoff of September 11, 2024) include:

mOS of 20.8 months, notably longer than the historical mOS of 7.5 and 8.4 months reported in historical third-party 2L R/M HNSCC trials: CheckMate 141 and KEYNOTE-040, respectively.
CUE-101 has been well tolerated as a monotherapy and in combination with pembrolizumab. No significant safety concerns have emerged in either the monotherapy or combination trials, and adverse events have been readily managed with appropriate medical care.

Key data highlights from the completed CUE-102 dose escalation and ongoing dose expansion parts of the Phase 1 clinical trial (data cutoff of October 29, 2024) include:

67% overall DCR in late-stage pancreatic cancer patients treated with CUE-102 at 2 and 4mg/kg, including an unconfirmed PR with a 40% decrease in tumor burden.
Evidence of selective stimulation and expansion of WT1-specific CD8 T cells, with no apparent increase in total numbers of non-specific CD8 T cells.
No dose-limiting toxicities occurred in patients treated during the dose escalation phase at doses ranging between 1-8mg/kg of CUE-102.
Matteo Levisetti, M.D., chief medical officer of Cue Biopharma, added, "We are pleased with the positive results from both the CUE-101 and CUE-102 ongoing trials as the data continue to mature. The CUE-102 data further demonstrates the mechanism of action of Immuno-STAT biologics to activate and expand tumor-specific T cells, as well as its translation into evidence of clinical benefit. The versatility of the Immuno-STAT platform holds significant potential for treating a variety of cancers."

All posters will be available to conference attendees as e-posters on the virtual meeting platform November 7, 2024, at 9 a.m. CST through January 7, 2025. The CUE-101 oral presentation and CUE-102 poster will also be available on November 8, 2024, in the Investors & Media section of the Company’s website at www.cuebiopharma.com, under Scientific Publications and Presentations.

About the CUE-100 Series
The CUE-100 series consists of Fc-fusion biologics that present two signals to T cells. Signal #1 is a tumor-specific peptide linked to a major histocompatibility complex (pMHC) to enable selectivity and specificity. Signal #2 is a rationally engineered interleukin 2 (IL-2) molecule to trigger T cell activation. These singular biologics are anticipated to selectively target, activate and expand a robust repertoire of tumor-specific T cells directly in the patient’s body. The binding affinity of IL-2 for its receptor has been deliberately attenuated to achieve preferential selective activation of tumor-specific effector T cells while reducing the potential for effects on regulatory T cells (Tregs) or broad systemic activation, potentially mitigating the dose-limiting toxicities associated with current IL-2-based therapies.

About CUE-101 and the Phase 1 trial
CUE-101 is Cue Biopharma’s lead clinical drug candidate from the CUE-100 series of interleukin 2 (IL-2)-based biologics. It is designed to activate and expand HPV16 tumor-specific T cells by presenting the HPV E7 protein to the HPV-specific T cell receptor. CUE-101 is currently being evaluated in a fully enrolled Phase 1 open-label, dose escalation and expansion study, for the treatment of HPV16+ driven recurrent/metastatic head and neck squamous cell carcinoma in second line (2L) and beyond patients as a monotherapy, and as a first line (1L) therapy in combination with pembrolizumab (KEYTRUDA).

About CUE-102 and the Phase 1 trial
CUE-102 is Cue Biopharma’s second clinical drug candidate from the CUE-100 series of interleukin 2 (IL-2)-based biologics. It is designed to activate and expand Wilms’ Tumor 1 (WT1)-specific T cells by presenting the WT1 peptide to the WT1- specific T cell receptor. WT1 is a well-recognized onco-fetal protein known to be over-expressed in a number of cancers, including solid tumors and hematologic malignancies. CUE-102 is being evaluated in a Phase 1 open label, two-part dose escalation and expansion study, for patients with late-stage colorectal, gastric/gastroesophageal junction, pancreatic and ovarian cancers that express WT1.

On November 8, 2024 Imugene Limited (ASX), a clinical-stage immuno-oncology company, reported the opening of the first Australian site for its azer-cel (azercabtagene zapreleucel) Phase 1b clinical trial (Press release, Imugene, NOV 8, 2024, https://mcusercontent.com/e38c43331936a9627acb6427c/files/6cb570ab-dadb-6cab-173b-2dd7797a4189/Imugene_Opens_First_Australian_Site_for_azer_cel_Trial.pdf [SID1234648039]). The Royal Prince Alfred Hospital in Sydney will begin patient recruitment in November 2024, marking another significant milestone in the development of this promising off-the-shelf allogeneic CAR T-cell therapy.

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This trial will be one of the only actively enrolling allogeneic CAR T-cell clinical trial in Australia, focusing on relapsed or refractory diffuse large B-cell lymphoma (DLBCL), a challenging form of non-Hodgkin’s lymphoma. Azer-cel represents a promising therapeutic option for patients whose cancers have not responded to other treatments, including autologous CAR T-cell therapies.

Azer-cel is an allogeneic, off-the-shelf CAR T-cell therapy that targets CD19, a protein commonly found on the surface of B-cells, including cancerous cells in DLBCL. Unlike traditional autologous CAR T therapies, which require harvesting and engineering a patient’s own T-cells, azer-cel uses donor T-cells, which are pre-manufactured and ready for use. This approach allows for quicker treatment and broader availability compared to autologous therapies that have long production times and logistical challenges.

Data to date from the trial, which has been dosing patients at US centres, has demonstrated promising results with three patients achieving complete responses (CR) even after failing multiple previous treatments, including autologous CAR T (see ASX announcement 2 September 2024). In particular, patients in Cohort B of the trial, who received a combination of azer-cel, lymphodepletion (chemotherapy)¹, and interleukin-2 (IL-2), showed robust clinical activity. Two out of three of the evaluable patients in this cohort experienced complete responses, with the durability of these responses extending beyond 90 and 120 days. These early results suggest that azer-cel could offer a meaningful alternative for patients with limited treatment options.

"We’re proud to be able to bring this trial to Imugene’s home country and provide an opportunity for Australian patients to benefit from this unique technology," said Imugene’s Managing Director and CEO Leslie Chong. " This is the first of up to five sites we plan to open in Australia, as we seek to speed up enrolment and deliver improved outcomes in this form of blood cancer."

On November 8, 2024 Medigene AG (Medigene or the "Company", FSE: MDG1, Prime Standard), an oncology platform company focused on the research and development of T cell receptor (TCR)-guided therapies for the treatment of cancer, reported recent advances in its proprietary End-to-End Platform to create optimal safe, sensitive, and specific (3S) T cell receptors that can be applied in various modalities, including therapies utilizing T cell receptor engineered T (TCR-T) cells, TCR-guided T cell engagers (TCR-TCEs) and TCR-natural killer cell therapies (TCR-NK) at the Cell 2024 Conference by Oxford Global taking place in London, UK from November 6-8, 2024 (Press release, MediGene, NOV 8, 2024, View Source [SID1234648038]).

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Data presented and discussed included

Kirsty Crame, MD, participated in the panel "Exploring Autologous vs. Allogeneic Therapies." which covered clinical insights, patient considerations, key immunological factors, and manufacturing challenges associated with each therapeutic approach.
Kirsty Crame, MD, held the keynote address "Making the Ordinary Extraordinary: MDG1015 A Clinic Ready 3rd Generation TCR-T Therapy" providing a comprehensive overview of MDG1015. MDG1015 is a first-in-class, 3rd generation T cell receptor engineered T cell (TCR-T) therapy targeting NY-ESO-1 / LAGE-1a, a well-recognized and validated cancer-testis antigen, which is expressed in multiple tumor types. MDG1015 received IND approval in Q3 2024 and is on track for CTA filing in Q4 2024.
Prof. Dolores Schendel presented the "TCR-T Platform for Solid Tumors" covering Medigene’s End-to-End Platform offering advanced technologies for developing 3S TCRs that can be utilized across multiple modalities. Precision tools enabling selection of 3S TCRs with high specificity, sensitivity, and safety for accurate tumor targeting were presented. Additionally, armoring and enhancement technologies were showcased which empower TCR-T cells to perform optimally within the challenging microenvironments of solid tumors. Furthermore, innovative tagging and tracing tools were highlighted, enabling seamless tracking of 3S TCRs throughout all phases of research and clinical development.
The presentations will be available on Medigene’s website: View Source

"Among other factors, the success of TCR-guided therapies for solid tumors hinges on several key innovations: developing optimal TCRs that are safe, sensitive, and specific; enhancing engineered cells to overcome the tumor microenvironment; and refining manufacturing strategies for optimized drug composition and timely patient delivery," said Dolores Schendel, Medigene’s Chief Scientific Officer. "Our E2E Platform addresses each of these critical areas, positioning us to deliver optimal 3S TCRs that can be utilized in multiple therapeutic modalities, such as TCR-T therapies, TCR-TCEs and TCR-NK cell therapies. This approach of developing different TCR-guided therapies enables us to provide innovative treatment options tailored to patients across various indications, disease stages, and specific individual needs."