On October 16, 2023 Starpharma (ASX: SPL, OTCQX: SPHRY) reported a copy of the DEP irinotecan combination data poster, showcasing the recently announced data for DEP irinotecan in combination with leading anticancer therapies, including immuno-oncology (IO) agents, in human colorectal cancer (CRC) models (Press release, Starpharma, OCT 16, 2023, View Source;mc_eid=bf52dd3418 [SID1234635974]). The data show that DEP irinotecan in combination with an IO agent or a PARP2 inhibitor demonstrated superior anti-tumour activity and significant survival benefit when compared to these agents delivered alone in multiple CRC models.

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The poster was presented over the weekend in Boston, US, at the international oncology conference, AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), co-hosted by the American Association of Cancer Research (AACR) (Free AACR Whitepaper), the National Cancer Institute (NCI) and the European Organisation for Research and Treatment of Cancer (EORTC) from 11 to 15 October 2023.

This promising combination data, together with the recently released positive clinical results for DEP irinotecan, provide a strong rationale for clinical evaluation of DEP irinotecan with these leading classes of cancer drugs. These combinations are commercially important because they increase the potential market opportunities for DEP irinotecan and illustrate valuable synergies with successful product categories.

On October 16, 2023 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, reported the publication of abstracts with data from the TACTI-002 and INSIGHT-003 trials in 1st line non-small cell lung cancer (1L NSCLC) at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (Press release, Immutep, OCT 16, 2023, View Source [SID1234635973]).

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TACTI-002 is a Phase II trial evaluating the chemotherapy-free combination of eftilagimod alpha ("efti") and KEYTRUDA (pembrolizumab), MSD’s (Merck & Co., Rahway, NJ, USA) anti-PD-1 therapy, in 1L NSCLC. The TACTI-002 abstract published by ESMO (Free ESMO Whitepaper), which contains data based on a cut-off date of 31 March 2023, showed an excellent initial survival benefit across an all-comer PD-L1 patient population in 1L NSCLC as well as for patients in each PD-L1 Tumour Proportion Score (TPS) subgroup, including 38.8 months in TPS >50%, 23.4 months in TPS 1-49%, and 25.0 months in TPS >1% (the OS result in TPS >1%, a key area of focus for future development where efti has FDA Fast Track designation, was already reported on May 17, 2023).

Notably, new updated data from TACTI-002, including more mature Overall Survival (OS) results, will be presented by Dr. Enric Carcereny, Catalan Institute of Oncology, Badalona (ICO), during a Mini Oral session (#1312MO) at ESMO (Free ESMO Whitepaper) Congress 2023 on Saturday, October 21, 2023, at 9:05 AM CEST.

INSIGHT-003 is an investigator-initiated Phase I trial conducted by the Frankfurt Institute of Clinical Cancer Research IKF evaluating efti in conjunction with KEYTRUDA and doublet chemotherapy in non-squamous 1L NSCLC patients. The data in the INSIGHT-003 abstract, with a cut-off date of 18 April 2023, showed a promising 67% overall response rate. Additionally, a Trials in Progress (TiP) abstract on the EFTISARC-NEO trial evaluating efti in combination with radiotherapy and KEYTRUDA titled has been published.

Abstracts are available on the ESMO (Free ESMO Whitepaper) website, and the mini oral presentation & posters will be available on Immutep’s website following their presentation.

Presentation Details

Title: Combining the antigen-presenting cell activator eftilagimod alpha (soluble LAG-3) and pembrolizumab: overall survival data from the 1st line non-small cell lung carcinoma (NSCLC) cohort of TACTI-002 (Phase II)

Presenter: Dr. Enric Carcereny, Catalan Institute of Oncology, Badalona (ICO)
Date and Time: Saturday, October 21, 2023; 9:10 AM CEST
Mini Oral session – NSCLC, metastatic
Presentation #1312MO
Title: INSIGHT-003 evaluating feasibility of eftilagimod alpha (soluble LAG-3) combined with 1st line chemo-immunotherapy in metastatic non-small cell lung cancer (NSCLC) adenocarcinomas

Speaker: Dr. Akin Atmaca, Krankenhaus Nordwest (IKF)
Date: Monday, October 23, 2023
Poster presentation, #1042P
Title: Pembrolizumab in combination with eftilagimod alpha and radiotherapy in neoadjuvant treatment of patients with soft tissue sarcomas – EFTISARC-NEO trial

Speaker: Dr. Katarzyna Kozak, Maria Skłodowska-Curie National Research Institute of Oncology
Date: Monday, October 23, 2023
Poster presentation, #1987TiP
Conference Call and Webcast:

Immutep will host a conference call and webcast to discuss the clinical data presented at ESMO (Free ESMO Whitepaper) 2023 and provide an overview on future clinical development plans for efti in 1st line non-small cell lung cancer. The event will feature Immutep CEO Marc Voigt, CSO Dr Frederic Triebel, CMO Dr Florian Vogl, and Christian Mueller, Senior Vice President Strategic Development. An open question & answer session with all presenters will conclude the event. A replay of the webcast will be available under the Events section of Immutep’s website.

Date/Time: Monday, October 23rd, at 8AM AEDT (Sunday, October 22nd, at 5PM ET)
Register: Link to register here
Questions: Investors are invited to submit questions in advance via [email protected].
KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About Eftilagimod Alpha (Efti)

Efti is Immutep’s proprietary soluble LAG-3 protein and MHC Class II agonist that stimulates both innate and adaptive immunity for the treatment of cancer. As a first-in-class antigen presenting cell (APC) activator, efti binds to MHC (major histocompatibility complex) Class II molecules on APC leading to activation and proliferation of CD8+ cytotoxic T cells, CD4+ helper T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-ƴ and CXCL10 that further boost the immune system’s ability to fight cancer.

Efti is under evaluation for a variety of solid tumours including non- small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy. Efti has received Fast Track Designation in 1st line HNSCC and in 1st line NSCLC from the United States Food and Drug Administration (FDA).

On October 15, 2023 Novocure (NASDAQ: NVCR) reported its participation in the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 from October 20 – 24 in Madrid (Press release, NovoCure, OCT 15, 2023, View Source [SID1234635982]). Novocure will present three new posters on Tumor Treating Fields (TTFields) therapy, including an analysis of patient-reported health-related global and functional quality of life scores from the randomized phase 3 LUNAR clinical trial in metastatic non-small cell lung cancer (NSCLC).

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The new analysis of data from LUNAR utilized The European Organization for Research and Treatment of Cancer Quality of Life questionnaire-C30. Analysis showed no statistically significant difference between patients who received TTFields therapy together with standard systemic therapies and patients who received standard systemic therapies alone in median time to deterioration for global health status (4.4 vs 4.0 months, P=0.91) and for all five functional scales: physical functioning (3.2 vs 4.2 months, P=0.58), role functioning (3.0 vs 2.8 months, P=0.59), emotional functioning (6.6 vs 5.7 months, P=0.96), cognitive functioning (3.7 vs 4.4 months, P=0.23), and social functioning (4.0 vs 3.9 months, P=0.66).

Highlights of Novocure’s presentations at the ESMO (Free ESMO Whitepaper) Congress 2023 also include global post-marketing surveillance data from patients with high-grade gliomas, confirming the well-tolerated safety profile of TTFields therapy in a subgroup of patients ages 70 and older in the real-world setting, which is consistent with data from Novocure’s EF-14 clinical trial. Another highlight is survey data from patients with glioblastoma (GBM) using TTFields therapy in the United States and DACH region (Germany, Austria and Switzerland), which showed that most patients were very satisfied or satisfied with TTFields therapy. Most said they would recommend TTFields therapy to a friend or acquaintance with GBM.

Novocure will also host an industry-sponsored symposium, titled The Evolving Role of TTFields Therapy in Solid Tumors, in Oviedo Auditorium, Hall 7, on Oct. 23 at 1 p.m. CEST.

"We are encouraged by new data supporting the use of TTFields therapy in the management of metastatic NSCLC and further validating the favorable safety and patient satisfaction profiles of TTFields therapy in patients with aggressive central nervous system tumors," said Pritesh Shah, Novocure’s Chief Growth Officer. "We look forward to sharing these insights with, and continuing to learn from, leading medical oncologists in Europe and worldwide."

Novocure’s full list of presentations at the ESMO (Free ESMO Whitepaper) Congress 2023 includes:

Post-marketing surveillance data from patients ≥70 years of age with central nervous system malignancies treated with Tumor Treating Fields (TTFields) therapy between 2011–2022. Presenter: Wenyin Shi. 12 p.m. CEST on Sunday, Oct. 22.
Tumor Treating Fields therapy for glioblastoma: Identifying needs and satisfaction of new and long-term users. Presenter: Eleni Batzianouli. 12 p.m. CEST on Sunday, Oct. 22.
Impact of TTFields therapy on global and functional health-related quality of life (HRQoL) in metastatic non-small cell lung cancer (mNSCLC) from the pivotal LUNAR study. Presenter: Joachim Aerts. 12 p.m. CEST on Monday, Oct. 23.
Symptom burden and health-related quality of life (HRQoL) in platinum-resistant or -refractory ovarian cancer (PROC): a systematic literature review (SLR). Presenter: Nikhila Indukuri. 12 p.m. CEST on Saturday, Oct. 21.
About Tumor Treating Fields Therapy

Tumor Treating Fields (TTFields) are electric fields that exert physical forces to kill cancer cells via a variety of mechanisms. TTFields do not significantly affect healthy cells because they have different properties (including division rate, morphology, and electrical properties) than cancer cells. The multiple, distinct mechanisms of TTFields therapy work together to selectively target and kill cancer cells. Due to its multimechanistic actions, TTFields therapy can be added to cancer treatment modalities in approved indications and demonstrates enhanced effects across solid tumor types when used with chemotherapy, radiotherapy, immune checkpoint inhibition, or targeted therapies in preclinical models. TTFields therapy provides clinical versatility that has the potential to help address treatment challenges across a range of solid tumors. To learn more about Tumor Treating Fields therapy and its multifaceted effect on cancer cells, visit tumortreatingfields.com.

On October 15, 2023 CatalYm reported new preclinical data expanding the mechanistic understanding of how GDF-15 plays a key role in cancer therapy resistance (Press release, Catalym, OCT 15, 2023, View Source [SID1234635981]). The results will be presented in a poster session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 in Madrid, Spain on Sunday, October 22nd by CatalYm’s CSO, Dr. Christine Schuberth-Wagner. The data are the first to show that GDF-15 has an inhibitory effect on the activation of M1 macrophages. These specific myeloid lineage immune cells are central to the initiation of immune responses, including the secretion of pro-inflammatory cytokines and chemokines, presentation of antigens as well as direct antitumor cytotoxicity.

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"The findings, therefore, provide additional support for the potential of GDF-15 neutralizing approaches as a critical component for treatment success in a broad range of anti-cancer regimens."

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The results support and expand on initial findings, recently published in Nature Communications, on pathways involved in the development of GDF-15 mediated therapy resistance in cancer cells. These data were the first to demonstrate a mechanistic link between GDF-15 and inhibition of the LFA-1/ICAM-1 cell adhesion axis in cancer, resulting in impaired infiltration of T cells into the tumor microenvironment.

"The ESMO (Free ESMO Whitepaper) data add to recently discovered mechanistic effects of GDF-15 impairing T cell infiltration into tumors and show the impairment of another important immune cell compartment by GDF-15, thereby expanding our understanding of its role in establishing tumor resistance to current cancer therapies. Interestingly, M1 macrophages are crucial for initiation of anti-tumoral immune responses and in parallel are active in tumor cell destruction by phagocytosis and oxidative stress," said Dr. Christine Schuberth-Wagner, Chief Scientific Officer at CatalYm. "The findings, therefore, provide additional support for the potential of GDF-15 neutralizing approaches as a critical component for treatment success in a broad range of anti-cancer regimens."

The preclinical data comprise in vitro analyses demonstrating that GDF-15 inhibits the polarization of M0 to M1 macrophages, indicated by a reduction of activation marker expression as well as MHC-II and Fcg-receptors. These phenotypic changes are accompanied by an altered cytokine expression and secretion profile. The activation was restored when GDF-15 was neutralized with CatalYm’s anti-GDF-15 antibody candidate, visugromab. In in vivo melanoma models, knock-out of GDF-15 led to an increase of counts and activation status of macrophages and antigen-presenting dendritic cells in tumor tissue. Overall, the results indicate that GDF-15 counteracts myeloid immune cell activation, supporting the generation of an immune-evasive tumor microenvironment, an important feature in therapy resistance.

CatalYm is investigating its GDF-15-neutralizing antibody visugromab in the GDFather (GDF-15 Antibody-mediaTed Human Effector Cell Relocation) trials in combination with the anti-PD-1 inhibitor nivolumab in patients with advanced solid tumors. Interim data from the Phase 2 (NCT04725474) trial recently presented at ASCO (Free ASCO Whitepaper) continue to demonstrate a very good safety and tolerability profile and promising durable, confirmed responses in major cancer indications, including non-small cell lung cancer (NSCLC), bladder cancer and hepatocellular carcinoma (HCC). The company expects to report mature data readouts for efficacy and safety from the core Phase 2a program as well as main biomarker-correlations before the end of 2023.

About Visugromab (CTL-002)

Visugromab is a monoclonal antibody that neutralizes the tumor-derived Growth Differentiation Factor-15 (GDF-15), a locally acting immunosuppressant fostering immunotherapy resistance. Neutralizing GDF-15 with visugromab reverses key cancer resistance mechanisms to reinstate an efficient anti-tumor response by reenabling immune cell activation and tumor infiltration. Visugromab has already demonstrated a good safety profile and potent and durable anti-tumor efficacy in combination with anti-PD-1 treatment in advanced cancer patients The antibody is currently being investigated in ongoing Phase 2 studies in multiple solid tumor indications.

On October 15, 2023 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, reported that it has entered into a clinical collaboration with AstraZeneca Investment (China) Co., Ltd. (or "AstraZeneca") (Press release, Ascentage Pharma, OCT 15, 2023, View Source [SID1234635979]). The two companies will jointly conduct a registrational Phase III study of the Bcl-2 inhibitor, APG-2575 (lisaftoclax), in combination with AstraZeneca’s Bruton’s tyrosine kinase (BTK) inhibitor, CALQUENCE (acalabrutinib), in treatment-naive patients with first-line chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

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This global multi-center, randomized-controlled, open-label, pivotal Phase III confirmatory trial is designed evaluate the efficacy and safety of lisaftoclax combined with acalabrutinib versus immunochemotherapy in patients with treatment-naïve CLL/SLL.

This collaboration marks another step-forward in the joint clinical development of the lisaftoclax plus acalabrutinib combination by Ascentage Pharma and AstraZeneca. In June 2020, Ascentage Pharma entered into a clinical collaboration with Acerta Pharma, a research and development center of the AstraZeneca Group, to jointly conduct a global Phase II study designed to assess the safety, tolerability, and efficacy of lisaftoclax, Ascentage Pharma’s investigational Bcl-2 selective inhibitor, in combination with acalabrutinib, Acerta Pharma’s BTK inhibitor. In the study, lisaftoclax combined with acalabrutinib showed strong therapeutic potential, with an objective response rate (ORR) of 98% in patients with relapsed/refractory (R/R) CLL/SLL, an ORR of 100% in treatment-naïve patients with CLL/SLL, and an excellent safety profile that is on par with that of lisaftoclax monotherapy[1]. Those results were released as an Oral Presentation at the 2022 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

CLL/SLL is a hematologic malignancy caused by mature B-cell neoplasms. Primarily affecting older populations, CLL/SLL is among the most common leukemia subtypes in adults and accounts for a quarter of all leukemia cases in the Western World, with over 100,000 new diagnoses reported globally each year[2]. In China, CLL/SLL is occurring at a rapidly rising incidence rate, with a younger age of onset and higher aggressiveness[3], thus posing a serious threat to public health in the country. Advancements in basic research and targeted therapies have brought meaningful survival benefit to patients with CLL/SLL. However, CLL/SLL still presents major clinical challenges and urgent medical needs for new treatment options that can offer both efficacy and safety.

Lisaftoclax is a novel, orally administered small-molecule Bcl-2 selective inhibitor being developed by Ascentage Pharma to treat malignancies by selectively blocking the antiapoptotic protein Bcl-2 and hence restoring the normal apoptosis process in cancer cells. With strong global best-in-class potential, lisaftoclax is the first Bcl-2 inhibitor in China and the second anywhere globally that has demonstrated compelling clinical activity and entered a pivotal registrational study. At present, lisaftoclax is being evaluated in multiple clinical studies across the world and more than 300 patients with CLL/SLL have already been treated with the drug. Interim results suggest that lisaftoclax, both as a monotherapy and in combination regimens, offers potent efficacy in patients with CLL/SLL and has the potential as a safer, more efficacious and more patient-friendly treatment option. It is also worth noting that in August 2023, lisaftoclax was cleared by the US Food and Drug Administration (FDA) to enter a global registrational Phase III study designed to assess the efficacy and safety of lisaftoclax combined with a BTK inhibitor in patients with CLL/SLL who have received prior therapies.

Acalabrutinib, a new generation highly selective BTK inhibitor that can specifically inhibit the BTK pathway, is a globally-adopted standard of care treatment for patients with CLL. In 2017, acalabrutinib was approved through the Priority Review process by the US Food and Drug Administration (FDA) for the second-line treatment of patients with mantle cell lymphoma (MCL), and subsequently in 2019, the drug was approved for the additional indication of adult patients with CLL/SLL. Meanwhile, acalabrutinib has been approved in more than 50 countries/regions, such as European Union and Japan until now. In China this year, acalabrutinib was sequentially approved for two indications that include patients with MCL who have received at least one prior therapy; and adult patients with CLL/SLL who have received at least one prior therapy.

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, "Combining Bcl-2 inhibitors and BTK inhibitors as a therapeutic approach has long attracted interest from both the research community and the industry. The Bcl-2 inhibitor lisaftoclax is a key drug candidate in Ascentage Pharma’s apoptosis-targeted pipeline. Results from the global Phase II study of lisaftoclax combined with acalabrutinib show that the combination regimen holds the promise as a patient-centric treatment strategy with enormous therapeutic potential. The clinical management of CLL/SLL overseas has already entered an era that is free of chemotherapies, and patients in China also desperately need a safer and more effective Bcl-2 inhibitor that can be combined with BTK inhibitors. Fulfilling our mission of addressing unmet clinical needs in China and around the world, we will work closely with AstraZeneca to actively advance this clinical development program of lisaftoclax and try to bring the drug to market as soon as possible for the benefit of more patients."

Ms. Haiying Yang, Vice President and Head of Medical Affairs at AstraZeneca China, commented, "Phase III results from the ASCENT, ELEVATE-TN, and ELEVATE-RR trials have solidified AstraZeneca’s position in the hematology field, while acalabrutinib-based combination regimens have been widely adopted as standard of care treatments. BTK inhibitors offer survival benefits to patients with lymphoma. However, there remains substantial clinical challenges in this therapeutic area and patients are in desperate need for new therapies that are both safe and efficacious, particularly fixed duration therapies. We are confident that acalabrutinib-based combinations can bring more effective and precision-targeting therapies to patients with hematologic malignancies in China as we take further steps in rendering hematologic malignancies into manageable chronic conditions. Through these innovative partnerships with local Chinese companies, we aspire to expand to more therapeutic areas and bring clinical benefit to a broader population of cancer patients in China."