Delving into the Latest Updates on M6223 with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Target

TIGIT

Action

inhibitors

Mechanism

TIGIT inhibitors(T cell immunoglobulin and ITIM domains inhibitors)

Therapeutic Areas

Neoplasms

Active Indication

Metastatic Solid Tumor

Inactive Indication-

Originator Organization

Merck KGaA

Active Organization

EMD Serono Research & Development Institute, Inc.

Inactive Organization

Merck KGaA

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

Login to view timeline

Structure/Sequence

Sequence Code 719618286

Sequence Code 719618285

A Phase II, Multicenter, Randomized, Open Label, Parallel-Arm, Umbrella Study of Avelumab (MSB0010718C) in Combination With Other AntiTumor Agents as a Maintenance Treatment in Participants With Locally Advanced or Metastatic Urothelial Carcinoma Whose Disease Did Not Progress With First Line Platinum-Containing Chemotherapy (JAVELIN Bladder Medley)

The purpose of this study is to assess the safety and efficacy of avelumab in combination with other anti-tumor agents as a maintenance treatment in participants with bladder cancer.

Start Date17 Aug 2022

Sponsor / Collaborator

EMD Serono Research & Development Institute, Inc.

[+1]

NCT04457778

/ CompletedPhase 1

Phase I, First-in-Human, Open-Label, Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Activity of M6223, an Inhibitor of TIGIT, as Single Agent and in Combination With Bintrafusp Alfa (Anti-PDL1/ TGFß Trap) in Participants With Metastatic or Locally Advanced Solid Unresectable Tumors

The main purpose of this study is to determine the safety, tolerability, pharmacokinetics (PK), immunogenicity and (if observed) the maximum tolerated dose (MTD) of M6223 as a single agent (Part 1A) for both the every 2 weeks (Q2W) regimen and the every 3 weeks (Q3W) regimen and of M6223 combined with bintrafusp alfa (Part 1B) for Q2W regimen in participants with metastatic or locally advanced solid unresectable tumors.

Start Date10 Jul 2020

Sponsor / Collaborator

EMD Serono Research & Development Institute, Inc.

[+1]

100 Clinical Results associated with M6223

Login to view more data

100 Translational Medicine associated with M6223

Login to view more data

100 Patents (Medical) associated with M6223

Login to view more data

2

Literatures (Medical) associated with M6223

01 Feb 2025·Journal for ImmunoTherapy of Cancer

TIGIT inhibitor M6223 as monotherapy or in combination with bintrafusp alfa in patients with advanced solid tumors: a first-in-human, phase 1, dose-escalation trial

Article

Author: Tolcher, Anthony ; Nogueira Filho, Marco A F ; Richter, Emilia ; Gleicher, Stephan ; McKean, Meredith ; Siu, Lillian L ; Tadjalli-Mehr, Keyvan ; Hu, Ping ; Victor, Anja ; Kitzing, Thomas ; Naing, Aung ; Gao, Wei ; Holland, Daniel

BackgroundM6223 is an intravenous (IV), Fc-competent, fully human, antagonistic, anti-T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) antibody. Bintrafusp alfa (BA) is a bifunctional fusion protein that simultaneously blocks nonredundant immunosuppressive TGF-β and PD-(L)1 pathways.MethodsThis first-in-human, dose-escalation study in patients with advanced solid tumors (N=58; aged ≥18 years, ECOG PS≤1) evaluated M6223 alone (Part 1A, n=40; M6223 10–2400 mg every 2 weeks, n=32; M6223 2400 mg every 3 weeks, n=8) or with BA (Part 1B, n=18; M6223 300–1600 mg with BA 1200 mg; both every 2 weeks, intravenous). Primary objectives were safety, tolerability, maximum tolerated dose (MTD) and recommended dose for expansion (RDE). Additional objectives included pharmacokinetics, pharmacodynamics and clinical activity (NCT04457778).ResultsTwo dose-limiting toxicities were observed: grade 3 adrenal insufficiency (Part 1A: M6223 900 mg every 2 weeks) and grade 3 anemia (Part 1B: M6223 300 mg, only BA related). MTD was not reached. Overall, median overall survival and progression-free survival were 7.6 (95% CI 4.9, 12.0) and 1.4 (95% CI 1.3, 1.8) months, respectively. Stable disease as best response was observed in 13 (32.5%) and 5 (27.8%) patients in parts 1A and 1B, respectively. M6223±BA displayed a linear pharmacokinetic profile. Anti-TIGIT mode-of-action-related pharmacodynamic effects were observed in peripheral blood and in tumor tissue. RDEs were 1600 mg every 2 weeks or 2400 mg every 3 weeks for M6223 monotherapy and 1600+1200 mg every 2 weeks for M6223+BA.ConclusionsM6223±BA had a manageable safety profile, with RDEs defined for both monotherapy and combination therapy. Further evaluation of M6223 is ongoing in combination with the PD-L1 inhibitor avelumab in patients with advanced urothelial carcinoma (JAVELIN Bladder Medley;NCT05327530).Trial registration numberNCT04457778.

01 Feb 2024·Future Oncology

The JAVELIN Bladder Medley Trial: Avelumab-Based Combinations as First-Line Maintenance in Advanced Urothelial Carcinoma

Article

Author: Hawley, Jessica ; Jacob, Natalia ; Hoffman-Censits, Jean ; Hahn, Noah M ; Mehr, Keyvan Tadjalli ; Seeberger, Sonja ; Powles, Thomas ; Grivas, Petros ; Guenther, Silke ; Tyroller, Karin

Results from JAVELIN Bladder 100 established avelumab (anti–PD-L1) first-line maintenance as the standard-of-care treatment for patients with advanced urothelial carcinoma (UC) that has not progressed with first-line platinum-based chemotherapy. We describe the design of JAVELIN Bladder Medley (NCT05327530), an ongoing phase II, multicenter, randomized, open-label, parallel-arm, umbrella trial. Overall, 252 patients with advanced UC who are progression-free following first-line platinum-based chemotherapy will be randomized 1:2:2:2 to receive maintenance therapy with avelumab alone (control group) or combined with sacituzumab govitecan (anti–Trop-2/topoisomerase inhibitor conjugate), M6223 (anti-TIGIT) or NKTR-255 (recombinant human IL-15). Primary end points are progression-free survival per investigator and safety/tolerability of the combination regimens. Secondary end points include overall survival, objective response and duration of response per investigator, and pharmacokinetics.

100 Deals associated with M6223

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Metastatic Solid Tumor	Phase 1	Canada	EMD Serono Research & Development Institute, Inc.	10 Jul 2020
Metastatic Solid Tumor	Phase 1	United States	EMD Serono Research & Development Institute, Inc.	10 Jul 2020
Solid tumor	Preclinical	United States	Merck KGaA	10 Jul 2020
Solid tumor	Preclinical	Canada	Merck KGaA	10 Jul 2020

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04457778 (Pubmed \| J Immunother Cancer) Manual	Phase 1	Advanced Malignant Solid Neoplasm	58	M6223 (Part 1A)	(lnxfdmnntk) = Two dose-limiting toxicities were observed: grade 3 adrenal insufficiency (Part 1A: M6223 900 mg every 2 weeks) and grade 3 anemia (Part 1B: M6223 300 mg, only BA related). tdnggmvcjw (bmepmckkws ) View more	Positive	01 Feb 2025
				M6223+bintrafusp alfa (Part 1B)
NCT04457778 (AACR2024) Manual	Phase 1	Solid tumor	58	M6223	(kqojlsfnyy) = Overall, two dose-limiting toxicities were observed: a grade 3 adrenal insufficiency (M6223, 900 mg) and a grade 3 anemia (M6223+BA, 300 mg; unrelated to M6223). hxhmctidva (krzfukduek ) View more	Positive	05 Apr 2024
				M6223+bintrafusp alfa
NCT04457778 (ESMO2022) Manual	Phase 1	Unresectable Solid Neoplasm TIGIT	41	M6223	(xrbgdulrxt) = nvthjahnyi pfxrlkpgjy (tijodngaoj ) View more	Positive	10 Sep 2022
				M6223+bintrafusp alfa	(xrbgdulrxt) = afgsuygyfn pfxrlkpgjy (tijodngaoj ) View more

Login to view more data

Translational Medicine

Boost your research with our translational medicine data.

login

or

view full example data

Boost your research with our translational medicine data.

Deal

Boost your decision using our deal data.

login

or

view full example data

Boost your decision using our deal data.

Core Patent

Boost your research with our Core Patent data.

login

or

view full example data

Boost your research with our Core Patent data.

Clinical Trial

Identify the latest clinical trials across global registries.

login

or

view full example data

Identify the latest clinical trials across global registries.

Approval

Accelerate your research with the latest regulatory approval information.

login

or

view full example data

Accelerate your research with the latest regulatory approval information.

Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

login

or

view full example data