Delving into the Latest Updates on Adakitug with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

ANTI-IL8 MAB, HuMax-IL8, HuMax-Inflam

+ [5]

Target

IL-8

Mechanism

IL-8 inhibitors(Interleukin-8 inhibitors)

Therapeutic Areas

NeoplasmsDigestive System DisordersRespiratory Diseases+ [2]

Active Indication

Solid tumorHepatocellular CarcinomaNon-Small Cell Lung Cancer+ [5]

Inactive Indication

Advanced Malignant Solid NeoplasmAutoimmune DiseasesCOVID-19+ [3]

Originator Organization

Medarex, Inc.

Active Organization

Bristol Myers Squibb Co.

Genmab A/S

Sino-American Shanghai Squibb Pharmaceuticals Ltd.

Inactive Organization

Medarex, Inc.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Gene Sequence

Sequence Code 431841641L

Source: *****

Sequence Code 431841640H

Source: *****

Background:
The myelodysplastic syndromes (MDS) are a group of bone marrow neoplasms. MDS mostly affect elderly people. The drugs used to treat MDS are not always effective, and the only curative treatment is stem cell transplant. Researchers want to see if a new drug can be used to treat MDS.
Objective:
To learn if HuMax-interleukin 8 (IL-8) BMS-986253 is a safe and effective treatment for MDS.
Eligibility:
Adults aged 18 and older with MDS.
Design:
Participants will be screened with a medical history, medication review, and physical exam. They will answer questions about how well they are able to take care of themselves. Their temperature, blood pressure, breathing rate, and heart rate will be monitored. They will have an electrocardiogram to see how well their heart is working. They will give blood and urine samples. They may have a bone marrow biopsy.
Participants will be assigned to a specific group. They will receive either BMS-986253 alone or in combination with deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi).
Treatment will be given in 28-day cycles. Participants will get BMS-986253 as an infusion on days 1 and 15 of each cycle. Some participants also will take oral DNMTi on days 2-6 of each cycle. They will receive treatment until their disease gets worse or they have bad side effects.
At study visits, some screening tests will be repeated. Some of the samples that are collected will be used for genetic testing.
About 30 days after treatment ends, participants will have a follow-up visit to see how they are doing. After that, follow up will occur via phone every 3-6 months until the study ends.
National Institutes of Health (NIH) will cover the costs for some travel expenses....

Start Date29 Nov 2022

Sponsor / Collaborator

National Cancer Institute

NCT04572451 / RecruitingPhase 1IIT

Phase I Study Investigating the Safety of Stereotactic Body Radiotherapy (SBRT) With Anti-PD1 and Anti-IL-8 for the Treatment of Multiple Metastases in Advanced Solid Tumors and Melanoma

Nivolumab (and other agents affecting the anti-programmed death-1 [anti-PD-1] pathway) have demonstrated anti-tumor activity in multiple tumor types. Combinations of immune-oncology (IO) agents with complimentary mechanisms as well as radiation represent a promising strategy to improve response rates to immunotherapy and overcome resistance. In this phase I/Ib study, radiation will be used in combination with IO agents nivolumab and anti-IL-8 (BMS-986253) to assess toxicity by organ system and then assess the preliminary efficacy of the treatment regimen. In Part 1, the study will determine the safe doses of radiation by organ site in conjunction with nivolumab and BMS-986253. In Part 2, the treatment regimen will be investigated in melanoma, prioritizing acral melanoma, to describe the response rate to treatment as well as other clinical and safety outcomes. The study will also provide the opportunity to evaluate changes in the tumor microenvironment induced by the treatment.

Start Date29 Nov 2021

Sponsor / Collaborator

University of Pittsburgh

[+1]

NCT04848116 / RecruitingPhase 2IIT

Neoadjuvant Targeting of Myeloid Cell Populations in Combination With Nivolumab in Head & Neck Cancer Patients Undergoing Surgery

The primary objective of this study is to assess safety and feasibility of pre-operative nivolumab in combination with BMS-986253 (anti-interleukin-8) in patients with squamous cell carcinoma of head and neck (SCCHN) who will undergo surgery.

Start Date24 Apr 2021

Sponsor / Collaborator

The Sidney Kimmel Comprehensive Cancer Center

[+1]

100 Clinical Results associated with Adakitug

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100 Translational Medicine associated with Adakitug

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100 Patents (Medical) associated with Adakitug

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3

Literatures (Medical) associated with Adakitug

01 Dec 2024·Computational and Structural Biotechnology Journal

A framework for the biophysical screening of antibody mutations targeting solvent-accessible hydrophobic and electrostatic patches for enhanced viscosity profiles

Article

Author: Burley, Glenn A ; Armstrong, Georgina B ; Shah, Vidhi ; Patel, Mitul ; Casey, Ricky ; Lewis, William ; Sanches, Paula ; Jamieson, Craig ; Rattray, Zahra

The formulation of high-concentration monoclonal antibody (mAb) solutions in low dose volumes for autoinjector devices poses challenges in manufacturability and patient administration due to elevated solution viscosity. Often many therapeutically potent mAbs are discovered, but their commercial development is stalled by unfavourable developability challenges. In this work, we present a systematic experimental framework for the computational screening of molecular descriptors to guide the design of 24 mutants with modified viscosity profiles accompanied by experimental evaluation. Our experimental observations using a model anti-IL8 mAb and eight engineered mutant variants reveal that viscosity reduction is influenced by the location of hydrophobic interactions, while targeting positively charged patches significantly increases viscosity in comparison to wild-type anti-IL-8 mAb. We conclude that most predicted in silico physicochemical properties exhibit poor correlation with measured experimental parameters for antibodies with suboptimal developability characteristics, emphasizing the need for comprehensive case-by-case evaluation of mAbs. This framework combining molecular design and triage via computational predictions with experimental evaluation aids the agile and rational design of mAbs with tailored solution viscosities, ensuring improved manufacturability and patient convenience in self-administration scenarios.

01 Dec 2019·Journal for ImmunoTherapy of CancerQ2 · MEDICINE

Phase I trial of HuMax-IL8 (BMS-986253), an anti-IL-8 monoclonal antibody, in patients with metastatic or unresectable solid tumors

Q2 · MEDICINE

ArticleOA

Author: Palena, Claudia ; Strauss, Julius ; Gulley, James L ; Gatti-Mays, Margaret E ; Marté, Jennifer L ; Bilusic, Marijo ; Donahue, Renee N ; Madan, Ravi A ; Collins, Julie M ; Heery, Christopher R ; Schlom, Jeffrey ; Karzai, Fatima

BACKGROUNDHuMax-IL8 (now known as BMS-986253) is a novel, fully human monoclonal antibody that inhibits interleukin-8 (IL-8), a chemokine that promotes tumor progression, immune escape, epithelial-mesenchymal transition, and recruitment of myeloid-derived suppressor cells. Studies have demonstrated that high serum IL-8 levels correlate with poor prognosis in many malignant tumors. Preclinical studies have shown that IL-8 blockade may reduce mesenchymal features in tumor cells, making them less resistant to treatment.METHODSFifteen patients with metastatic or unresectable locally advanced solid tumors were enrolled in this 3 + 3 dose-escalation trial at four dose levels (4, 8, 16, or 32 mg/kg). HuMax-IL8 was given IV every 2 weeks, and patients were followed for safety and immune monitoring at defined intervals up to 52 weeks.RESULTSAll enrolled patients (five chordoma, four colorectal, two prostate, and one each of ovarian, papillary thyroid, chondrosarcoma, and esophageal) received at least one dose of HuMax-IL8. Eight patients had received three or more prior lines of therapy and five patients had received prior immunotherapy. Treatment-related adverse events occurred in five patients (33%), mostly grade 1. Two patients receiving the 32 mg/kg dose had grade 2 fatigue, hypophosphatemia, and hypersomnia. No dose-limiting toxicities were observed, and maximum tolerated dose was not reached. Although no objective tumor responses were observed, 11 patients (73%) had stable disease with median treatment duration of 24 weeks (range, 4-54 weeks). Serum IL-8 was significantly reduced on day 3 of HuMax-IL8 treatment compared to baseline (p = 0.0004), with reductions in IL-8 seen at all dose levels.CONCLUSIONSHuMax-IL8 is safe and well-tolerated. Ongoing studies are evaluating the combination of IL-8 blockade and other immunotherapies.TRIAL REGISTRATIONNCTN, NCT02536469. Registered 23 August 2015, https://clinicaltrials.gov/ct2/show/NCT02536469?term=NCT02536469&rank=1 .

02 Nov 2017·JCI InsightQ1 · MEDICINE

Neutralization of IL-8 decreases tumor PMN-MDSCs and reduces mesenchymalization of claudin-low triple-negative breast cancer

Q1 · MEDICINE

ArticleOA

Author: Palena, Claudia ; Dominguez, Charli ; David, Justin M. ; McCampbell, Kristen K.

The complex signaling networks of the tumor microenvironment that facilitate tumor growth and progression toward metastatic disease are becoming a focus of potential therapeutic options. The chemokine IL-8 is overexpressed in multiple cancer types, including triple-negative breast cancer (TNBC), where it promotes the acquisition of mesenchymal features, stemness, resistance to therapies, and the recruitment of immune-suppressive cells to the tumor site. The present study explores the utility of a clinical-stage monoclonal antibody that neutralizes IL-8 (HuMax-IL8) as a potential therapeutic option for TNBC. HuMax-IL8 was shown to revert mesenchymalization in claudin-low TNBC models both in vitro and in vivo as well as to significantly decrease the recruitment of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) at the tumor site, an effect substantiated when used in combination with docetaxel. In addition, HuMax-IL8 enhanced the susceptibility of claudin-low breast cancer cells to immune-mediated lysis with NK and antigen-specific T cells in vitro. These results demonstrate the multifaceted way in which neutralizing this single chemokine reverts mesenchymalization, decreases recruitment of MDSCs at the tumor site, assists in immune-mediated killing, and forms the rationale for using HuMax-IL8 in combination with chemotherapy or immune-based therapies for the treatment of TNBC.

100 Deals associated with Adakitug

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05484

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced cancer	Phase 2	DE	Bristol Myers Squibb Co.	12 Feb 2018
Advanced cancer	Phase 2	PL	Bristol Myers Squibb Co.	12 Feb 2018
Advanced cancer	Phase 2	ES	Bristol Myers Squibb Co.	12 Feb 2018
Advanced cancer	Phase 2	SE	Bristol Myers Squibb Co.	12 Feb 2018
Advanced cancer	Phase 2	CA	Bristol Myers Squibb Co.	12 Feb 2018
Advanced cancer	Phase 2	FR	Bristol Myers Squibb Co.	12 Feb 2018
Liver Cancer	Phase 2	-	Genmab A/S	-
Non-Small Cell Lung Cancer	Phase 2	-	Genmab A/S	-
Autoimmune Diseases	Preclinical	-	Medarex, Inc.	-
Psoriasis	Preclinical	-	-	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03400332 (ESMO_IO2022) Manual	Phase 1/2	Advanced cancer	159	BMS-986253+nivolumab	(mlnhtqmqmu) = zkiqxeyyep mujqrntngz (kefdfqzuvj ) View more	Positive	08 Dec 2022
NCT03400332 (ESMO_IO2022) Manual	Phase 1/2	Advanced cancer	159	BMS-986253+ipilimumab+nivolumab	(azeegullsg) = vlfpovxqxn qixjmkwyyr (zjkxgipxen ) View more	Positive	08 Dec 2022
NCT03689699 (MAGIC-8, ASCO2022) Manual	Phase 1/2	Castration-Resistant Prostatic Cancer	59	degarelix acetate+nivolumab	qocbsuqcns(elonxjdqir) = dfkendydbj qsassrkelp (zsebponfes ) View more	Positive	02 Jun 2022
NCT03689699 (MAGIC-8, ASCO2022) Manual	Phase 1/2	Castration-Resistant Prostatic Cancer	59	degarelix acetate+nivolumab+BMS-986253	qocbsuqcns(elonxjdqir) = jnjeydxgzg qsassrkelp (zsebponfes ) View more	Positive	02 Jun 2022
NCT02536469 (Pubmed \| J Immunother Cancer) Manual	Phase 1	Solid tumor	15	HuMax-IL8	(ualeuqoeoo) = vdytxnznck gzwmqolbiw (mnmfiwjhrg ) View more	Positive	05 Sep 2019
NCT02536469 (ASCO2018)	Phase 1	Metastatic Solid Tumor	15	BMS-986253	(ymtfykgbrr) = no serious treatment-related adverse events (TRAEs) were observed and MTD was not identified through 32mg/kg. TRAEs occurred in 5 pts (33%), and all were Grade 1 except for Grade 2 fatigue, hypophosphatemia and hypersomnia in two patients receiving 32mg/kg hyszgiuopa (uslmvtpagv )	Positive	01 Jun 2018