更新于：2024-12-11

Aldesleukin

阿地白介素

更新于：2024-12-11

概要

概要

基本信息

药物类型

白细胞介素

别名

125-L-Serine-2-133-interleukin 2、IL-2 (Chiron)、Interleukin-2 (Chiron)

+ [12]

靶点

IL-2R

作用机制

IL-2R激动剂(白细胞介素-2受体复合体激动剂)、免疫刺激剂

治疗领域

肿瘤泌尿生殖系统疾病皮肤和肌肉骨骼疾病+ [5]

在研适应症

肾细胞癌复发性神经母细胞瘤转移性恶性黑色素瘤+ [13]

非在研适应症

急性嗜碱性粒细胞白血病急性嗜酸细胞白血病急性红细胞白血病+ [85]

原研机构

Chiron Corp.

在研机构

Clinigen

National Cancer InstituteClinigen Healthcare Ltd.

+ [7]

非在研机构

Barbara Ann Karmanos Cancer Institute

National Institute on AgingNational Institutes of Health Clinical Center

最高研发阶段批准上市

首次获批日期

美国 (1992-05-05),

肾细胞癌

最高研发阶段(中国)临床1期

特殊审评孤儿药 (韩国)、孤儿药 (美国)

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序列信息

Sequence Code 720

来源: *****

关联

421

项与阿地白介素相关的临床试验

NCT06690281 / Not yet recruiting临床2期IIT

A Phase II Study of Adjuvant Immunotherapy Targeting KRAS G12D, KRAS G12V, or TP53 R175H for Participants With Advanced Gastrointestinal Malignancies

Background:
Gastrointestinal (GI) cancer affects the organs (such as the stomach, large and small intestine, pancreas, colon, liver, and biliary system) of the digestive tract. In some participants who have had surgery for GI cancer, blood tests show that the cancer has spread despite being unable to be identified by scans. Certain gene mutations (changes) in GI cancer (such as KRAS or TP53) can be targeted by T cells, a type of immune cell, in individuals with specific HLA types (genes that help proteins in the body know what is self and non-self). Researchers want to see if they can stop GI cancer from returning or spreading in people with these gene mutations and specific HLA types.
Objective:
To test therapy with modified T-cells to prevent or delay the return of GI cancer after standard treatment. T-cells play a role in the body s immune system.
Eligibility:
People aged 18 to 72 years with GI cancer that was treated with standard therapy and is not seen on imaging scans. They must have specific gene mutations and HLA types. They also must have certain clinical or blood tests showing the cancer is spreading (elevating CA19-9 or detectable ctDNA).
Design:
Participants will be divided into 2 groups. Participants nor the study team can choose what Group to participate in; this is done by randomization , like flipping a coin. Participants will have a 1-to-1 chance of being in Group 1 or Group 2.
Group 1 will receive T-cell therapy. Their own T-cells will be collected. In a lab, the cells will be combined with a virus that carries a protein to target cancer cells.
Group 1 participants will stay in the hospital for 3 weeks or more. They will have chemotherapy, and their modified T-cells will be infused through a tube attached to a needle inserted into a vein.
Group 1 participants will visit the clinic every 3 months for 1 year and then every 6 months for 5 years. Then they will have follow-up visits for another 10 years under a different protocol.
Group 2 participants will not receive treatment with T-cells. They will visit the clinic every 3 months for 1 year and then every 6 months for 5 years.

开始日期2025-01-01

申办/合作机构

National Cancer Institute

NCT06626256 / Not yet recruiting临床1期IIT

A Phase 1 Safety and Efficacy Study of STIL101 for Injection in Locally Advanced, Unresectable, or Metastatic Pancreatic Ductal Adenocarcinoma, Colorectal Cancer, Renal Cell Carcinoma, Cervical Cancer, and Melanoma

This phase I trial tests the safety and side effects of STIL101 for injection and how well it works in treating patients with pancreatic cancer, colorectal cancer (CRC), renal cell cancer (RCC), cervical cancer (CC) and melanoma that has spread to nearby tissue or lymph nodes (locally advanced) or to other places in the body (metastatic) or that cannot be removed by surgery (unresectable). STIL101 for injection, an autologous (made from the patients own cells) cellular therapy, is made up of specialized white blood cells called lymphocytes or "T cells" collected from a piece of the patients tumor tissue. The T cells collected from the tumor are then grown in a laboratory to create STIL101 for injection. STIL101 for injection is then given to the patient where it may attack the tumor. Giving chemotherapy, such as cyclophosphamide and fludarabine, helps prepare the body to receive STIL101 for injection in a way that allows the T cells the best opportunity to attack the tumor. Aldesleukin is a form of interleukin-2, a cytokine made by leukocytes. Aldesleukin increases the activity and growth of white blood cells called T lymphocytes and B lymphocytes. Giving STIL101 for injection may be safe, tolerable and/or effective in treating patients with locally advanced, metastatic or unresectable pancreatic cancer, CRC, RCC, CC and melanoma.

开始日期2024-12-30

申办/合作机构

City of Hope National Medical Center

[+1]

NCT05639972 / Not yet recruiting临床1/2期IIT

A Feasibility Study of E7 TCR-T Cell Induction Therapy for Locoregionally Advanced HPV-Associated Cancers

The goal of this study is to determine the feasibility of administration of a single dose of E7 TCR-T cells as induction therapy prior to definitive treatment (chemoradiation or surgery) of locoregionally advanced HPV-associated cancers. The intent of E7 TCR-T cell treatment is to shrink or eliminate tumors and thereby facilitate definitive therapy and increase overall survival.
This study seeks to determine 1) if E7 TCR-T cells can be administered without undue delay in definitive treatment, 2) the tumor response rate to E7 TCR-T cell treatment, and 3) the disease-free survival rate at 2 and 5 years.
Participants will undergo an apheresis procedure to obtain T cells that will be genetically engineered to generate E7 TCR-T cells. They will receive a conditioning regimen, a single infusion of their own E7 TCR-T cells, and adjuvant aldesleukin. Participants will follow up to assess safety and determine tumor response and will return to their primary oncology team for definitive therapy.

开始日期2024-10-12

申办/合作机构

Rutgers State University of New Jersey

100 项与阿地白介素相关的临床结果

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100 项与阿地白介素相关的转化医学

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100 项与阿地白介素相关的专利（医药）

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2,992

项与阿地白介素相关的文献（医药）

2024-12-31·mAbs

Discovery and development of ANV419, an IL-2/anti-IL-2 antibody fusion protein with potent CD8+ T and natural killer cell-stimulating capacity for cancer immunotherapy

Article

作者: Regnier, Catherine ; Rondeau, Jean-Michel ; Popp, Simone ; Katopodis, Andreas ; Egli, Nicole ; Richter, Kirsten ; Huber, Christoph ; Murer, Patrizia ; Petersen, Laetitia ; Brannetti, Barbara

Novel engineered IL-2 agonists strive to increase the therapeutic window of aldesleukin (human IL-2) by increasing selectivity toward effector over regulatory T cells and reducing dose-limiting toxicities. Here we describe ANV419, an IL-2/anti-IL2 antibody fusion protein designed for selective IL-2 receptor βγ (IL-2 Rβγ) activation by sterically hindering IL-2 from binding to IL-2 Rα. The fusion protein has an IL-2 connected to the light chain complementarity-determining region (CDR) domain of a humanized antibody that binds to IL-2 at the same epitope as IL-2 Rα. Optimization of the selectivity and pharmacological properties led to the selection of ANV419. ANV419 preferentially expands CD8⁺ T cells and natural killer (NK) cells over T_regs and can be safely administered at doses that elicit strong pharmacodynamic effects and efficacy in mouse tumor models. Its anti-tumor efficacy was enhanced when combined with programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint inhibitors. ANV419 also enhances the NK cell killing capacity and increases tumor growth inhibition when used alongside trastuzumab in a Her-2⁺ xenograft mouse model. In cynomolgus monkeys, the estimated half-life of ANV419 is 24 h, and doses that induced sustained expansion of effector cells were well tolerated without the severe toxicities typically observed with high-dose IL-2. These data support the clinical development of ANV419 in solid tumors and hematological malignancies as monotherapy and in combination with checkpoint inhibitors or agents that induce antibody-dependent cellular cytotoxicity. ANV419 is currently in Phase 1/2 clinical development and may provide cancer patients with a wider therapeutic window than aldesleukin.

2024-11-01·Rheumatology (Oxford, England)

Where are we now in biologic drugs for myositis?

Review

作者: Isenberg, David A ; Neves, Ana ; Viveiros, Luísa ; Venturelli, Veronica

Abstract:

Idiopathic inflammatory myopathies (IIMs) are a rare and heterogeneous group of chronic autoimmune disorders. Up to 40% of IIM patients have long-term sequelae and significant functional disability. Its management can be challenging and new therapies are badly needed. The small number of cases with diverse presentations and different diagnostic criteria significantly affect clinical trial results. Only IVIG has been internationally approved for IIM patients. Most clinical trials of new biologic therapies have failed to meet their primary endpoints in IIM, with only one biologic drug recommended for refractory IIM treatment (rituximab), although not approved. We review several new emerging biologic drugs, including B cell depletion therapies, abatacept, Janus kinase inhibitors, and aldesleukin. Encouragingly, some phase II randomized controlled trials have evaluated the efficacy and safety of new biologics in IIM, demonstrating an improvement in clinical and laboratory measures.

2024-11-01·IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY

Immunosuppressive effects of triptolide via interleukin-2/receptor signaling

Article

作者: Ding, Yanxia ; Wang, Juan ; Lv, Jiagang ; Darshika Kodithuwakku, Nandani ; Xiong, Ying ; Yin, Yi ; Chen, Jiao

BACKGROUND:

Triptolide (TP) has been confirmed to possess many beneficial functions including anti-inflammation and immunosuppression.

OBJECTIVE:

The present study aimed to explore the potential involvement of IL-2/IL-2R pathway in the immunosuppressive activities of TP.

METHODS:

Cultured CTLL-2 cells were utilized to evaluate the potential benefits of TP. Then cell viability was determined by CCK-8 assay, IFN-γ level by ELISA assay, Annexin V-FITC/PI double-staining and CD25 expression by flow cytometry, and protein expression by western blotting. Additionally, rhIL-2-driven lymphocytes following ConA activation were investigated. The interactions of TP with IL-2 and IL-2Rα were investigated by binding assays and molecular dynamics simulations.

RESULTS:

TP treatment attenuated IFN-γ level and cell viability in both rhIL-2-induced CTLL-2 cells and rhIL-2-driven splenic lymphocytes. TP treatment increased cellular apoptosis/necrosis and cleaved PARP-1 level, while suppressed c-Myc level in rhIL-2-induced CTLL-2 cells. Additionally, TP treatment reduced CD25 expression on CTLL-2 cell surface. Notably, the phosphorylation protein levels in IL-2R signaling pathways were inhibited by TP exposure prior to rhIL-2 stimulation. SPR and BLI assays verified TP that directly bound to rhIL-2 and rmIL-2Rα, respectively. Molecular simulations suggested that TP bound at the interface of IL-2 and IL-2Rα near the hydrophobic patch composed of F62, L92 on IL-2 and L23, I46, V139 on IL-2Rα, resulting in decreased binding free energy between IL-2 and IL-2Rα.

CONCLUSIONS:

These findings collectively emphasized that TP interfered IL-2/IL-2Rα interactions, down-regulated IL-2Rα expression, and inhibited IL-2R signaling pathways activation, thereby leading to the immune cells being desensitized to rhIL-2 and exhibiting immunosuppressive properties.

119

项与阿地白介素相关的新闻（医药）

2024-12-05

·GlobeNewswire-Health Care

Medicenna Provides Clinical Update and Announces First Complete Responder in MDNA11 and KEYTRUDA® (pembrolizumab) Combination Dose Escalation Arm of the ABILITY-1 Study

70-year-old patient with advanced chemo-refractory anal cancer achieves complete response (CR) in 8 weeks when treated with MDNA11 in combination with Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) Complete regression of all tumors in two CPI-resistant patients in monotherapy arms continue to show durability with a patient with melanoma remaining tumor free at week 63 while a patient with pancreatic cancer remains off all anti-cancer therapy for 11 months after completing the study A patient with advanced MSS colorectal cancer with a previously announced partial response (PR) continues treatment in the combination escalation arm as of week 32 with a confirmed PR Both objective responses (1 CR and 1PR) among evaluable patients in the combination dose escalation arm (N=9) are in tumor types with high unmet need and where checkpoint inhibitors (CPI) have not been approved The ABILITY-1 study is showing promising disease control rates (DCR = CR+PR+SD) of 55% (1 CR, 4 PRs, and 6 SDs) and 78% (1 CR, 1 PR and 5 SDs) in the monotherapy and combination arms, respectfully Additional monotherapy and combination clinical data from the ABILITY-1 study will be presented at medical conferences in Q1 and Q2 of 2025 TORONTO and HOUSTON, Dec. 05, 2024 (GLOBE NEWSWIRE) -- Medicenna Therapeutics Corp. (“Medicenna” or the “Company”) (TSX: MDNA, OTCQX: MDNAF), a clinical-stage immunotherapy company focused on the development of Superkines, announced that updated clinical data from the ongoing Phase 1/2 ABILITY-1 study were presented today at the 2024 Immunotherapy Bridge held in Naples, Italy. The oral presentation by Dr Arash Yavari, MB BS, DPhil, included new data highlighting the first complete response (CR) in the combination dose escalation phase of the study in a 70-year-old patient with advanced anal squamous cell carcinoma (anal SCC), in addition to follow up safety and efficacy results from the monotherapy and combination arms of the ABILITY-1 study. The anal SCC patient previously progressed on two prior lines of treatment comprising of chemotherapy combination and chemo-radiation treatments. The patient achieved a 100% reduction of all measurable target and non-target lesions by Week 8, highlighting MDNA11’s potential to enhance checkpoint inhibitor efficacy in advanced solid tumor types traditionally considered less sensitive to immunotherapy. “These remarkable results from our monotherapy and early data from the combination dose escalation highlights the transformative potential of MDNA11 as a combination therapy with checkpoint inhibitors like KEYTRUDA®, while demonstrating an acceptable safety profile as dose escalation continues,” said Fahar Merchant, PhD, President and CEO of Medicenna. “Achieving a complete response in a patient with anal squamous cell carcinoma, a cancer with historically low immunotherapy response rates, demonstrates MDNA11’s ability to reinvigorate the immune system and tackle difficult-to-treat tumors. We look forward to sharing additional clinical data at medical conferences in Q1 and Q2 of 2025 as we advance MDNA11 as a potent and safe immunotherapy to dramatically improve current immunotherapies and deliver life-changing outcomes for patients.” Key findings from the on-going ABILITY-1 study (data cut-off as of November 18th, 2024) include: Safety Profile MDNA11 has a favorable safety profile both as a monotherapy and in combination with KEYTRUDA®. Over 90% of treatment-related adverse events (TRAEs) were Grade 1-2 and transient, with no DLTs or new safety signals observed in combination dose escalation cohorts. MDNA11 at doses of 120 µg /kg (Q3W monotherapy; Q2W and Q3W in combination with Keytruda (400 mg Q6W) are currently being evaluated. Immunodynamics MDNA11 preferentially expands immune effector cells, including activated (CD25+) and “stemness-like” (TCF-1+) CD8+ T cells, which are critical for sustained anti-tumor responses.Robust, dose-dependent lymphocyte expansion in combination with KEYTRUDA®, sustained with repeat MDNA11 dosing. Monotherapy Tumor Response in Immune Checkpoint Inhibitor-Resistant Patients MDNA11 continues to demonstrate encouraging deep and durable single-agent anti-tumor activity among patients who progressed on prior ICI therapy: An objective response rate (ORR) of 30% in the monotherapy dose expansion arm with 3 PRs among 10 patients who had all previously failed ICI therapy and had advanced and/or metastatic melanoma, non-melanoma skin cancer or MSI-H/dMMR tumors. The ORR is 25% from a total of 20 patients when including 10 phase 2 eligible patients from the MDNA11 monotherapy dose escalation arm who received at least 60 µg/kg MDNA11 and were ICI-resistant.Overall, objective responses in ICI-resistant patients include 1 CR and 4 PRs 2 PRs among 3 MSI-H patients (ORR of 66.7%) with both responders having metastatic pancreatic ductal adenocarcinoma (PDAC).1 CR and 2 PRs among 11 patients with cutaneous melanoma (ORR of 27.3%). Complete resolution of all target and non-target lesions in two patients: 1 confirmed CR in a melanoma patient continues on treatment as of week 63.Pancreatic cancer patient (MSI-H) achieved complete resolution of target and non-target metastatic lesions in the liver including a new lesion treated with MDNA11 following a single cycle of radiation, achieved durable response for 20 months during the study and continues to remain off anti-cancer therapy for 11 months. SD in 6 patients for a disease control rate (DCR = CR+PR+SD) of 55% including 3 with duration > 6 months, yielding a clinical benefit rate of 40% (8/20). MDNA11 Combination with KEYTRUDA® Tumor Response The objective of the combination dose escalation/evaluation portion of the ABILITY-1 study is to assess the safety, pharmacokinetics and immunodynamics of MDNA11 at various doses and dosing regimens when combined with KEYTRUDA® (400mg, Q6W), and to determine the recommended dose and schedule for the combination dose expansion portion of the study. Encouraging preliminary signs of anti-tumor activity have been observed with MDNA11 in combination with KEYTRUDA® to date in dose escalation cohorts 1 (60 µg/kg Q2W MDNA11) and 2 (90 µg/kg Q2W MDNA11). Among 9 heavily pre-treated, efficacy-evaluable patients, tumor control was observed in 7 patients for a DCR of 78% including a CR in an anal squamous cell carcinoma patient and PR in a microsatellite-stable (MSS) colorectal cancer patient. CR in a 70-year-old male with anal squamous cell carcinoma Patient progressed on 2 prior lines of chemotherapy (1L capecitabine/mitomycin plus radiation therapy; 2L carboplatin/paclitaxel)CR achieved on first study evaluable imaging scan at Week 8; patient continues on combination treatment Confirmed PR in 52-year-old female with MSS colorectal cancer Patient progressed on 2 prior lines of chemotherapy (1L folinate/fluorouracil/oxaliplatin; 2L capecitabine)Continues on combination treatment as of week 32 A copy of the presentation has been posted on the “Scientific Presentations” page of Medicenna’s website. About MDNA11 MDNA11 is an intravenously administered, long-acting, ‘beta-enhanced not-alpha’ IL-2 Superkine specifically engineered to overcome the shortcomings of aldesleukin and other next generation IL-2 variants by preferentially activating immune effector cells (CD8+ T and NK cells) responsible for killing cancer cells, with minimal or no stimulation of immunosuppressive Tregs. These unique proprietary features of the IL-2 Superkine have been achieved by incorporating seven specific mutations and genetically fusing it to a recombinant human albumin scaffold to improve the pharmacokinetic (PK) profile and pharmacological activity of MDNA11 due to albumin’s natural propensity to accumulate in highly vascularized sites, in particular tumor and tumor draining lymph nodes. MDNA11 is currently being evaluated in the Phase 1/2 ABILITY-1 study as both monotherapy and in combination with KEYTRUDA®. About the ABILITY-1 Study The ABILITY-1 study (NCT05086692) is a global, multi-center, open-label study that assesses the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of MDNA11 as monotherapy or in combination with KEYTRUDA®. In the combination dose escalation portion of the Phase 2 study, approximately 20 patients are expected to be enrolled and administered ascending doses of MDNA11 intravenously in combination with KEYTRUDA®. This portion of the study includes patients with a wide range of solid tumors with the potential for susceptibility to immune modulating therapeutics. Upon identification of an appropriate dose regimen for combination, the study will proceed to combination dose expansion. About Medicenna Therapeutics Medicenna is a clinical-stage immunotherapy company focused on developing novel, highly selective versions of IL-2, IL-4 and IL-13 Superkines and first-in-class Empowered Superkines. Medicenna’s long-acting IL-2 Superkine, MDNA11, is a next-generation IL-2 with superior affinity toward CD122 (IL-2 receptor beta) and no CD25 (IL-2 receptor alpha) binding, thereby preferentially stimulating cancer-killing effector T cells and NK cells. MDNA11 is being evaluated in the Phase 1/2 ABILITY-1 Study (NCT05086692) as a monotherapy and in combination with KEYTRUDA®. Medicenna’s IL-4 Empowered Superkine, bizaxofusp (formerly MDNA55), has been studied in 5 clinical trials enrolling over 130 patients, including a Phase 2b trial for recurrent GBM, the most common and uniformly fatal form of brain cancer. Bizaxofusp has obtained FastTrack and Orphan Drug status from the FDA and FDA/EMA, respectively. Medicenna’s early-stage high-affinity IL-2β biased IL-2/IL-15 Super-antagonists, from its MDNA209 platform, are being evaluated as potential therapies for autoimmune and graft-versus host diseases. Medicenna’s early-stage BiSKITs™ (Bifunctional SuperKine ImmunoTherapies) and the T-MASK™ (Targeted Metalloprotease Activated SuperKine) programs are designed to enhance the ability of Superkines to treat immunologically “cold” tumors. For more information, please visit www.medicenna.com, and follow us on Twitter and LinkedIn. Forward-Looking Statements This news release may contain forward-looking statements within the meaning of applicable securities laws. Forward-looking statements include, but are not limited to, express or implied statements regarding the future operations of the Company, estimates, plans, strategic ambitions, partnership activities and opportunities, objectives, expectations, opinions, forecasts, projections, guidance, outlook or other statements that are not historical facts, such as statements on the therapeutic treatment potential and safety profile of MDNA11 (both as monotherapy and in combination with KEYTRUDA®) and the timing and/or release of any additional clinical updates. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage pre-clinical or clinical studies may not be indicative of full results or results from later stage or larger scale clinical studies and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented. Forward-looking statements are often identified by terms such as “will”, “may”, “should”, “anticipate”, “expect”, “believe”, “seek”, “potentially” and similar expressions. and are subject to risks and uncertainties. Forward-looking statements are based on a number of assumptions believed by the Company to be reasonable at the date of this news release. Although the Company believes that the expectations reflected in such forward-looking statements are reasonable, there can be no assurance that such statements will prove to be accurate. These statements are subject to certain risks and uncertainties and may be based on assumptions that could cause actual results and future events to differ materially from those anticipated or implied in such statements. Important factors that could cause actual results to differ materially from the Company’s expectations include the risks detailed in the latest annual information form of the Company and in other filings made by the Company with the applicable securities regulators from time to time in Canada. The reader is cautioned that assumptions used in the preparation of any forward-looking information may prove to be incorrect. Events or circumstances may cause actual results to differ materially from those predicted, as a result of numerous known and unknown risks, uncertainties, and other factors, many of which are beyond the control of the Company. The reader is cautioned not to place undue reliance on any forward-looking information. Such information, although considered reasonable by management, may prove to be incorrect and actual results may differ materially from those anticipated or implied in forward-looking statements. Forward-looking statements contained in this news release are expressly qualified by this cautionary statement. The forward-looking statements contained in this news release are made as of the date hereof and except as required by law, we do not intend and do not assume any obligation to update or revise publicly any of the included forward-looking statements. This news release contains hyperlinks to information that is not deemed to be incorporated by reference in this new release. Investor and Company Contact: Christina CameronInvestor Relationsir@medicenna.com(647) 953-0673 Daniel ScarrInvestor Relations & Business Developmentdscarr@medicenna.com(647) 220-4509

临床结果免疫疗法临床2期孤儿药放射疗法

2024-11-29

·GlobeNewswire-Health Care

Updated MDNA11 Monotherapy and Combination Clinical Data from the Ongoing Phase 1/2 ABILITY-1 Study to be Presented at the 2024 Immunotherapy Bridge Conference

Nov. 27, 2024 -- Medicenna Therapeutics Corp. (“Medicenna” or the “Company”) (TSX: MDNA, OTCQX: MDNAF), a clinical-stage immunotherapy company focused on the development of Superkines, announced today that updated clinical data from the ongoing Phase 1/2 ABILITY-1 study will be presented as part of an oral podium presentation at the 2024 Immunotherapy Bridge Conference, taking place from December 4-5, 2024 in Naples, Italy. The oral presentation will include updated clinical data from the monotherapy and combination arms of the ongoing Phase 1/2 ABILITY-1 Study evaluating MDNA11, a long-acting ‘beta-enhanced not-alpha’ interleukin-2 (“IL-2”) super-agonist, in patients with advanced or metastatic solid tumors. Title: Updated Safety and Efficacy Results from the First-in-Human Study of MDNA11 (ABILITY-1), a Next Generation ‘Beta-Enhanced Not-Alpha’ IL-2 Superkine, Show Single-Agent Activity in Patients with Advanced Solid Tumors Presentation Date: Thursday, December 5, 2024 8:45 AM CET (2:30 AM EST) Presenter: Dr. Arash Yavari, MBBS, DPhil; Director of Clinical Strategy Following the presentation, a copy of the presentation will be available on the “Scientific Presentations” page of Medicenna’s website. MDNA11 is an intravenously administered, long-acting ‘beta-enhanced not-alpha’ IL-2 Superkine specifically engineered to overcome the shortcomings of aldesleukin and other next generation IL-2 variants by preferentially activating immune effector cells (CD8+ T and NK cells) responsible for killing cancer cells, with minimal or no stimulation of immunosuppressive Tregs. These unique proprietary features of the IL-2 Superkine have been achieved by incorporating seven specific mutations and genetically fusing it to a recombinant human albumin scaffold to improve the pharmacokinetic (PK) profile and pharmacological activity of MDNA11 due to albumin’s natural propensity to accumulate in highly vascularized sites, in particular tumor and tumor draining lymph nodes. MDNA11 is currently being evaluated in the Phase 1/2 ABILITY-1 study as both monotherapy and in combination with pembrolizumab. The ABILITY-1 study (NCT05086692) is a global, multi-center, open-label study that assesses the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of MDNA11 as monotherapy or in combination with pembrolizumab. In the combination dose escalation portion of the Phase 2 study, approximately 20 patients are expected to be enrolled and administered ascending doses of MDNA11 intravenously in combination with pembrolizumab. This portion of the study includes patients with a wide range of solid tumors with the potential for susceptibility to immune modulating therapeutics. Upon identification of an appropriate dose regimen for combination, the study will proceed to a combination dose expansion cohort. Medicenna is a clinical-stage immunotherapy company focused on developing novel, highly selective versions of IL-2, IL-4 and IL-13 Superkines and first-in-class Empowered Superkines. Medicenna’s long-acting IL-2 Superkine, MDNA11, is a next-generation IL-2 with superior affinity toward CD122 (IL-2 receptor beta) and no CD25 (IL-2 receptor alpha) binding, thereby preferentially stimulating cancer-killing effector T cells and NK cells. MDNA11 is being evaluated in the Phase 1/2 ABILITY-1 Study (NCT05086692) as a monotherapy and in combination with pembrolizumab. Medicenna’s IL-4 Empowered Superkine, bizaxofusp (formerly MDNA55), has been studied in 5 clinical trials enrolling over 130 patients, including a Phase 2b trial for recurrent GBM, the most common and uniformly fatal form of brain cancer. Bizaxofusp has obtained FastTrack and Orphan Drug status from the FDA and FDA/EMA, respectively. Medicenna’s early-stage high-affinity IL-2β biased IL-2/IL-15 Super-antagonists, from its MDNA209 platform, are being evaluated as potential therapies for autoimmune and graft-versus host diseases. Medicenna’s early-stage BiSKITs™ (Bifunctional SuperKine ImmunoTherapies) and the T-MASK™ (Targeted Metalloprotease Activated SuperKine) programs are designed to enhance the ability of Superkines to treat immunologically “cold” tumors. The content above comes from the network. if any infringement, please contact us to modify.

免疫疗法孤儿药临床结果

2024-11-27

·aulosbio.com

Aulos Bioscience Doses First Patient in Phase 2 Cohort Evaluating the Combination of Avelumab and AU-007 for the Treatment of Non-Small Cell Lung Cancer

Press Releases In the News Media Inquiries Videos LARKSPUR, Calif., November 27, 2024 – Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through development of potentially best-in-class IL-2 therapeutics, today announced dosing of the first patient with AU-007, avelumab, a PD-L1 antibody with Fc effector function, and low-dose, subcutaneous aldesleukin in a Phase 2 cohort focused on the second-line treatment of PD-L1+ non-small cell lung cancer (NSCLC). The Phase 2 cohort is a clinical trial collaboration with Ares Trading S.A., a Swiss subsidiary of Merck KGaA, Darmstadt, Germany, and part of Aulos’ Phase 1/2 clinical trial of AU-007. “We are excited to move forward with evaluating this combination therapy in a clinical setting after seeing encouraging synergy with AU-007 and a surrogate model of avelumab in preclinical studies including complete elimination of established solid tumors,” said Aron Knickerbocker, Aulos Bioscience’s president and chief executive officer. “Avelumab’s profile, coupled with AU-007 and low-dose, subcutaneous aldesleukin, could potentially offer a new therapeutic option for patients with advanced or metastatic PD-L1+ non-small cell lung cancer that has progressed following first-line therapy with a checkpoint inhibitor. We thank Merck KGaA, Darmstadt, Germany, the patients and the clinical trial investigators who have chosen to participate in this clinical trial.” In May, Aulos announced a collaboration and supply agreement with Ares Trading S.A., a Swiss subsidiary of Merck KGaA, Darmstadt, Germany, for use of avelumab in combination with AU-007 and low-dose, subcutaneous aldesleukin in an additional Phase 2 cohort of the AU-007 Phase 1/2 clinical trial. Avelumab is a human anti-programmed death ligand-1 (PD-L1) antibody approved for use in multiple tumor types. Avelumab is the only approved PD-L1 or PD-1 antibody with Fc effector function, and has been shown in vitro to engage natural killer (NK) cells to kill tumor cells by a process known as antibody-dependent cellular cytotoxicity (ADCC), while also interrupting the PD-1/PD-L1 pathway that inhibits effector T cell (Teff) function. AU-007 is the first human IgG1 monoclonal antibody designed by leveraging artificial intelligence to enter a human clinical trial. In preclinical studies, strong anti-cancer activity, including complete tumor eradications, was observed when AU-007 was dosed with a single loading dose of human interleukin-2 (hIL-2) and an anti-PD-L1 surrogate of avelumab. The AU-007 Phase 1/2 study is currently enrolling patients with unresectable locally advanced or metastatic cancer at multiple clinical trial site locations in the United States and Australia. Positive Phase 1 and preliminary Phase 2 data presented at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting earlier this month shows evidence of AU-007’s anti-tumor activity. Preliminary Phase 2 data reveal that a combination of AU-007 and low-dose, subcutaneous aldesleukin is clinically active in melanoma. Additionally, data from all 77 patients show durable Treg reduction – a compelling result in the IL-2 class – and correlated progression-free survival. Aulos plans to share preliminary data from the Phase 2 cohort studying AU-007 with avelumab and low-dose, subcutaneous aldesleukin as a second-line treatment for PD-L1+ NSCLC in the first half of 2025. About AU-007 AU-007 is a human IgG1 monoclonal antibody designed by leveraging artificial intelligence that is highly selective to the CD25-binding portion of IL-2. With a mechanism of action unlike any other IL-2 therapeutic in development, AU-007 redirects IL-2 to reinforce anti-tumor immune effects. This is achieved by preventing IL-2, either exogenous or secreted by effector T cells, from binding to trimeric receptors on regulatory T cells while still allowing IL-2 to bind and expand effector T cells and NK cells. This prevents the negative feedback loop caused by other IL-2-based treatments and biases the immune system toward activation over suppression. AU-007 also prevents IL-2 from binding to CD25-containing receptors on eosinophils, as well as vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy. To learn more about the AU-007 Phase 1/2 clinical trial program, including study locations in the United States and Australia, please visit ClinicalTrials.gov (identifier: NCT05267626), www.solidtumorstudy.com (U.S.) and www.solidtumourstudy.com (Australia). About Aulos Aulos Bioscience is an immuno-oncology company working to revolutionize cancer patient care through best-in-class IL-2 therapeutics that direct patients’ immune systems toward killing tumor cells. Matching world-class machine learning from co-founder Biolojic Design with an in-depth understanding of the immune system, Aulos’ initial clinical candidate, AU-007, is a human antibody designed by leveraging artificial intelligence that harnesses the power of IL-2 to induce tumor killing while limiting the immunosuppression and toxicities typically associated with this validated pathway. The company was founded by Biolojic Design and Apple Tree Partners (ATP) and is led by pioneers in the field of artificial intelligence, antibody development and cancer immunotherapies. For more information, visit www.aulosbio.com, X (@AulosBioscience) and LinkedIn. Contact: info@aulosbio.com Media inquiries: Mike Beyer, Sam Brown Inc. / 312-961-2502 / mikebeyer@sambrown.com

临床2期免疫疗法上市批准ASCO会议

100 项与阿地白介素相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00748	-	L03AC01	DB00041

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
肾细胞癌	美国	Chiron Corp.	1992-05-05

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
高风险神经母细胞瘤	临床3期	美国	National Cancer Institute	2009-12-21
难治性霍奇金淋巴瘤	临床3期	美国	National Cancer Institute	2003-11-01
难治性霍奇金淋巴瘤	临床3期	澳大利亚	National Cancer Institute	2003-11-01
难治性霍奇金淋巴瘤	临床3期	加拿大	National Cancer Institute	2003-11-01
复发性神经母细胞瘤	临床3期	美国	National Cancer Institute	2001-10-18
复发性神经母细胞瘤	临床3期	澳大利亚	National Cancer Institute	2001-10-18
复发性神经母细胞瘤	临床3期	加拿大	National Cancer Institute	2001-10-18
复发性神经母细胞瘤	临床3期	新西兰	National Cancer Institute	2001-10-18
复发性神经母细胞瘤	临床3期	波多黎各	National Cancer Institute	2001-10-18
急性嗜碱性粒细胞白血病	临床3期	美国	National Cancer Institute	2000-11-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03318900 (CTgov)	临床1/2期	复发性卵巢癌 \| 铂耐药性卵巢癌	5	Cyclophosphamide+IL-2 (Dose Level 1)	繭壓餘餘鹹廠願鑰壓網(淵鹹鑰遞廠獵網選觸鏇) = 膚鑰糧繭鏇鏇淵積鏇獵鹹簾蓋壓遞壓鹽壓壓願 (鏇顧鏇蓋遞鬱糧遞鹹範, 顧築選鬱廠構鬱鬱積簾 ~ 遞網壓觸鏇獵蓋獵窪選) 更多	-	2024-11-07
				Cyclophosphamide+IL-2 (Dose Level 2)	繭壓餘餘鹹廠願鑰壓網(淵鹹鑰遞廠獵網選觸鏇) = 鏇築願艱餘壓範製積餘鹹簾蓋壓遞壓鹽壓壓願 (鏇顧鏇蓋遞鬱糧遞鹹範, 鑰鏇膚構鬱蓋艱構鏇積 ~ 願築壓艱夢夢糧築廠繭) 更多
NCT05267626 (SITC2024) 人工标引	临床1/2期	晚期恶性实体瘤	-	AU-007	願鬱夢鹽簾繭遞繭襯廠(鬱膚鑰顧網壓構襯鹽蓋) = None 艱鑰構艱憲鏇淵鬱壓襯 (鏇網鹹蓋襯鏇鑰蓋廠遞 ) 更多	积极	2024-11-05
				AU-007 + aldesleukin
NCT02027935 (CTgov)	临床2期	转移性黑色素瘤	16	Autologous CD8+ Melanoma Specific T Cells+ipilimumab+Cyclophosphamide+Aldesleukin	鑰鑰齋構蓋壓構製廠襯(憲壓網獵遞齋淵襯鹹蓋) = 選憲廠齋壓憲築艱觸鹹艱獵蓋顧蓋鑰醖窪選鏇 (鹽淵顧艱窪鹽繭壓積網, 顧網鹹艱夢餘窪網簾構 ~ 憲齋膚淵繭廠衊醖餘鑰) 更多	-	2024-10-08
NCT03007238 (CTgov)	临床2期	慢性移植物抗宿主病 \| 类固醇难治性移植物抗宿主病	10	ECP (Treatment (ECP+IL-2))	繭築餘構遞衊築窪構遞(繭構窪窪顧鑰壓鑰壓憲) = 繭願鹹齋齋願蓋壓窪製願構遞衊夢襯鬱艱構願 (網憲鑰夢簾膚鏇觸繭鹽, 獵範衊餘廠顧築鏇齋選 ~ 鏇壓獵醖鏇窪觸鹹餘積) 更多	-	2024-04-08
				ECP (Overall Study)	顧壓衊製積鹹鏇觸膚艱(選膚鹽餘艱獵簾齋艱壓) = 積顧獵壓築築願觸願積鏇製廠鏇築齋鹹壓淵鹽 (壓鏇願鏇鏇顧淵觸襯網, 網範夢醖窪壓艱繭鏇淵 ~ 積觸網願齋遞淵夢顧鑰) 更多
NCT01856023 (PROCLIVITY02, CTgov)	临床4期	转移性黑色素瘤	29	ipilimumab+High Dose Interleukin-2 (Treatment Arm 1)	繭鑰獵齋簾鬱鹹襯構餘(鹹鏇夢壓願膚廠選餘繭) = 衊製選鹽壓齋艱願蓋積簾觸艱壓夢願顧範廠衊 (艱選蓋襯築窪鏇糧遞鏇, 齋積鑰衊窪醖窪鹽選淵 ~ 糧鹹簾餘鏇獵獵鏇夢構)	-	2023-12-05
				ipilimumab+High Dose Interleukin-2 (Treatment Arm 2)	繭鑰獵齋簾鬱鹹襯構餘(鹹鏇夢壓願膚廠選餘繭) = 鹹選壓遞構顧窪齋遞淵簾觸艱壓夢願顧範廠衊 (艱選蓋襯築窪鏇糧遞鏇, 鏇範廠夢襯遞夢繭衊簾 ~ 廠淵網糧淵鏇願膚鬱鬱)
NCT02620865 (CTgov)	临床1/2期	转移性胰腺腺癌 \| 晚期胰腺腺癌	2	Laboratory Biomarker Analysis+Paclitaxel Albumin-Stabilized Nanoparticle Formulation+Leucovorin Calcium+Gemcitabine Hydrochloride+Sargramostim+Aldesleukin+Oxaliplatin+Irinotecan Hydrochloride+fluorouracil	淵鏇壓製廠觸艱淵網顧(簾鹹觸膚鬱壓鹽顧餘艱) = 糧夢範構淵艱廠餘觸鑰選願遞遞製廠齋醖願鏇 (觸糧遞顧積廠蓋獵製觸, 鏇遞窪糧鹽夢顧築糧顧 ~ 襯艱鹽網繭範積鑰餘繭) 更多	-	2023-05-15
NCT02748564 (CTgov)	临床2期	皮肤黑色素瘤 \| 头颈部黏膜黑色素瘤 \| 转移性黑色素瘤 ... 更多	10	Laboratory Biomarker Analysis+pembrolizumab+Aldesleukin	襯艱鹹積遞簾鏇願願衊(憲獵構窪壓淵築範憲艱) = 選夢齋餘淵憲鏇構築願積襯壓觸鹹艱膚顧顧顧 (顧醖齋鏇遞網積獵鏇窪, 窪齋鏇醖簾顧鹽窪範築 ~ 積齋積積顧選簾鏇繭鬱) 更多	-	2023-02-09
Tandem Meetings ASTCT and CIBMTR2023	N/A	类固醇难治性移植物抗宿主病	15	Low Dose Interleukin-2 (LD IL-2)	顧鬱繭鑰齋範築夢繭願(夢壓製製齋窪憲鏇艱膚) = Two deaths occurred; one patient with advanced hepatic dysfunction due to cGVHD and one patient with poor graft function at the time of IL-2 start 膚簾鏇構築廠顧繭憲襯 (築廠顧製繭壓網選糧積 ) 更多	积极	2023-02-01
LITE trial (EASL2022)	临床4期	维持 CD4+CD25+Foxp3+	6	Low dose interleukin-2 (LDIL-2)	膚壓夢廠鹽鹹範鹹膚齋(願鏇選鏇積廠願觸壓顧) = The trial was terminated after the first six trial participants failed to reach the primary end point due to rejection requiring immunosuppression reinstitution 蓋艱築壓構窪餘憲憲鹹 (遞壓鹽積壓觸壓顧餘積 ) 更多	不佳	2022-06-25
NCT03113773 (Pubmed) 人工标引	临床1/2期	心肌缺血	41	Proleukin	築蓋簾選衊鹹遞壓選構(範選構鹽壓顧網網網製) = The majority of adverse events were mild. 積鹹繭鏇壓築憲襯餘選 (鬱壓夢蓋憲觸繭醖夢齋 ) 更多	积极	2022-01-09
				Placebo