A Phase 1/2, First-in-Human, Open-label, Dose Escalation Study of GB1275 Monotherapy and in Combination With an Anti-PD-1 Antibody in Patients With Specified Advanced Solid Tumors or in Combination With Standard of Care in Patients With Metastatic Pancreatic Adenocarcinoma, Followed by Basket Expansion of GB1275 With Standard of Care or in Combination With an Anti-PD-1 Antibody in Patients With Specified Metastatic Solid Tumors

This first-in-human (FIH ) study is an open-label, multicenter study that consists of a Phase 1 Dose Escalation/Expansion phase of GB1275 monotherapy or in combination with Anti-PD-1 Antibody or in combination with Standard of Care in Patients with Metastatic Pancreatic Adenocarcinoma followed by a Phase 2 Basket Expansion phase in Patients with Specified Metastatic Solid Tumors

Start Date13 Aug 2019

Sponsor / Collaborator

GB006, Inc.

[+1]

100 Clinical Results associated with GB-1275

100 Translational Medicine associated with GB-1275

100 Patents (Medical) associated with GB-1275

Literatures (Medical) associated with GB-1275

01 Jun 2023·Cancer Cell

Context-dependent activation of STING-interferon signaling by CD11b agonists enhances anti-tumor immunity

Article

Author: Kang, Liang-I ; Fields, Ryan C ; Hogg, Graham D ; Galkin, Anna V ; Mpoy, Cedric ; Knolhoff, Brett L ; Osterhout, Robin E ; Gupta, Vineet ; Ahmad, Faiz ; Vij, Kiran R ; Lander, Varintra E ; Park, Haeseong ; Baer, John M ; Liu, Xiuting ; Borcherding, Nicholas C ; Zuo, Chong ; Bruey, Jean-Marie ; DeNardo, David G ; Carter, Laura L ; Schwarz, Julie K

Chronic activation of inflammatory pathways and suppressed interferon are hallmarks of immunosuppressive tumors. Previous studies have shown that CD11b integrin agonists could enhance anti-tumor immunity through myeloid reprograming, but the underlying mechanisms remain unclear. Herein we find that CD11b agonists alter tumor-associated macrophage (TAM) phenotypes by repressing NF-κB signaling and activating interferon gene expression simultaneously. Repression of NF-κB signaling involves degradation of p65 protein and is context independent. In contrast, CD11b agonism induces STING/STAT1 pathway-mediated interferon gene expression through FAK-mediated mitochondrial dysfunction, with the magnitude of induction dependent on the tumor microenvironment and amplified by cytotoxic therapies. Using tissues from phase I clinical studies, we demonstrate that GB1275 treatment activates STING and STAT1 signaling in TAMs in human tumors. These findings suggest potential mechanism-based therapeutic strategies for CD11b agonists and identify patient populations more likely to benefit.

01 Nov 2021·Journal for ImmunoTherapy of CancerQ2 · MEDICINE

Correction: GB1275, a first-in-class CD11b modulator: rationale for immunotherapeutic combinations in solid tumors

Q2 · MEDICINE

ArticleOA

01 Aug 2021·Journal for ImmunoTherapy of CancerQ2 · MEDICINE

GB1275, a first-in-class CD11b modulator: rationale for immunotherapeutic combinations in solid tumors

Q2 · MEDICINE

ReviewOA

Author: Zhou, Lei ; Bendell, Johanna ; Dupont, Jakob ; DeNardo, David G ; Galkin, Anna

Resistance to immune checkpoint inhibitors (ICI) and other anticancer therapies is often associated with the accumulation of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). Therefore, targeting MDSC recruitment or function is of significant interest as a strategy to treat patients with ICI-resistant cancer. The migration and recruitment of MDSCs to the TME is mediated in part by the CD11b/CD18 integrin heterodimer (Mac-1; αMβ2), expressed on both MDSCs and TAMs. However, inhibition or blockade of CD11b/CD18 has had limited success in clinical trials to date, likely since saturation of CD11b requires doses that are not clinically tolerable with the agents tested so far. Interestingly, activation of CD11b with leukadherin-1 was found to reduce macrophage and neutrophil migration in animal models of inflammatory conditions. Preclinical studies with GB1275, a salt form of leukadherin-1, demonstrated that activation of CD11b improves the antitumor immune response and enhances the response to immunotherapy in mouse models of pancreatic adenocarcinoma, breast cancer and lung cancer. Based on the promising results from preclinical studies, a phase 1/2 clinical study (NCT04060342) of GB1275 in patients with advanced solid tumor types known to be resistant or less likely responsive to immuno-oncology therapies, including pancreatic, breast, prostate, and microsatellite-stable colorectal cancer, is ongoing. In this review, we examine targeting MDSCs as a therapeutic approach in cancer therapy, with a special focus on GB1275 preclinical studies laying the rationale for the phase 1/2 clinical study.

100 Deals associated with GB-1275

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Solid tumor	Preclinical	US	Gossamer Bio, Inc.	27 Apr 2020
Solid tumor	Preclinical	GB	Gossamer Bio, Inc.	27 Apr 2020
Gastroesophageal junction adenocarcinoma	Preclinical	GB	GB006, Inc.	13 Aug 2019
Gastroesophageal junction adenocarcinoma	Preclinical	GB	Merck Sharp & Dohme Corp.	13 Aug 2019
Gastroesophageal junction adenocarcinoma	Preclinical	US	GB006, Inc.	13 Aug 2019
Gastroesophageal junction adenocarcinoma	Preclinical	US	Merck Sharp & Dohme Corp.	13 Aug 2019
Renal Cell Carcinoma	Preclinical	US	Merck Sharp & Dohme Corp.	13 Aug 2019
Renal Cell Carcinoma	Preclinical	GB	GB006, Inc.	13 Aug 2019
Renal Cell Carcinoma	Preclinical	US	GB006, Inc.	13 Aug 2019
Renal Cell Carcinoma	Preclinical	GB	Merck Sharp & Dohme Corp.	13 Aug 2019

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04060342 (KEYNOTE A36, ASCO2021) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	45	GB1275	(dcbtwdnzrf) = No DLTs were reported. xwyaktwufi (uwwxfacxah ) View more	Positive	20 May 2021
				Pembrolizumab+GB1275

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

GB-1275

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation