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."

On November 8, 2024 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune disorders, reported initial preclinical data for FT836, a multiplexed-engineered, chimeric antigen receptor (CAR) T-cell product candidate targeting major histocompatibility complex (MHC) proteins A (MICA) and B (MICB) at the 2024 Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting being held in Houston, TX on November 6-10, 2024 (Press release, Fate Therapeutics, NOV 8, 2024, View Source [SID1234648037]). The expression of MICA/B cell-surface proteins is induced by cellular stress or malignant transformation, and is detectable across many types of cancer cells with limited expression on healthy tissue. FT836 incorporates multiple next-generation synthetic controls of CAR T-cell function including the Company’s novel Sword & Shield technology, which is comprised of a constellation of genetic edits that both target and evade host alloreactive immune cells and is designed to promote functional persistence of off-the-shelf CAR T-cell therapies without conditioning chemotherapy.

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"The novel suite of synthetic controls incorporated into FT836 is intended to address critical challenges that have limited CAR T-cell safety and efficacy in treating solid tumors including on-target, off-tumor toxicity, effector cell suppression in the tumor microenvironment, tumor heterogeneity, and limited functional persistence," said Bob Valamehr, Ph.D., President of Research & Development of Fate Therapeutics. "Our FT836 preclinical data presented today at SITC (Free SITC Whitepaper) support the pan-cancer activity of MICA/B targeting, and indicate that our next-generation, iPSC-derived CAR T-cell platform has the potential to drive potent and durable anti-tumor activity without the need for administration of conditioning chemotherapy to deplete host immune cells."

Preclinical Data

MICA/B targeting is emerging as a novel cancer-specific strategy to attack a wide range of solid tumors, however, proteolytic cleavage and shedding of MICA/B at the membrane-proximal α3 domain is a common mechanism of cancer resistance and escape from canonical NKG2D-mediated recognition. FT836 is designed to uniquely target and bind the α3 domain, which has been shown to stabilize MICA/B expression and induce robust cytolytic killing of tumor cells. At an oral presentation today at SITC (Free SITC Whitepaper) entitled "Development of an Off-the-Shelf, MICA/B Targeting CAR T Cell to Overcome Pan-tumor Escape Mechanism for Solid Tumors", scientists from the Company highlighted that FT836 exerted potent and durable anti-tumor activity in vivo across a broad array of solid tumors. In addition, treatment of tumor cells with chemotherapy or radiation therapy in vitro elicited an increase in MICA/B expression and further enhanced the cytolytic activity of FT836, indicating the potential for combination with standard-of-care regimens used for the treatment of solid tumors.

Novel Sword & Shield Technology

FT836 is also the Company’s first product candidate to incorporate its novel Sword & Shield technology, which utilizes a 4-1BB-targeted CAR (ADR) alongside the complete knock-out of CD58 (CD58KO), to both target and evade host alloreactive immune cells. In preclinical studies presented at SITC (Free SITC Whitepaper), iPSC-derived Sword & Shield CAR T cells demonstrated functional persistence and durable anti-tumor activity in vivo that was uniquely maintained upon supraphysiological challenge with alloreactive T cells, indicating the potential of Sword & Shield CAR T cells to thrive without administration of conditioning chemotherapy to deplete host immune cells. The Company’s novel Sword & Shield technology was also featured in a poster presentation at SITC (Free SITC Whitepaper) entitled "Alloimmune Defense Receptor Combined with Genetic Ablation of Adhesion Ligand CD58 is a Comprehensive Approach to Promote Functional Persistence of Allogeneic Cell Therapies without Conditioning Chemotherapy".