This open-label, non-randomized Phase II trial is designed to assess the safety and tolerability of GT103 in combination with pembrolizumab in adult subjects with relapsed or refractory, metastatic NSCLC. The study will consist of a safety lead-in of 10-20 patients. A total of 50 patients will be treated with the combination at the safest dose of GT103 as determined in the safety lead-in. If 10 additional patients are enrolled to the dose level -1 then the maximum of 60 subjects may be accrued to this trial.

Start Date17 Feb 2023

Sponsor / Collaborator

Duke University

[+2]

NCT04314089

/ Active, not recruitingPhase 1IIT

Phase Ib First in Human Dose Escalation of GT103 in Refractory, Advanced Stage Non-Small Cell Lung Cancer (TOP 1902)

The purpose of this research study is to determine the maximum tolerated dose of GT103 and investigate the safety and effectiveness of the study drug.

Start Date09 Jun 2020

Sponsor / Collaborator

Duke University

100 Clinical Results associated with GT-103

100 Translational Medicine associated with GT-103

100 Patents (Medical) associated with GT-103

Literatures (Medical) associated with GT-103

15 May 2024·The Journal of Immunology

Promotion of an Antitumor Immune Program by a Tumor-specific, Complement-activating Antibody

Article

Author: Guo, Jian ; Bushey, Ryan T. ; Saxena, Ruchi ; Patz, Jr, Edward F. ; He, You-Wen ; Campa, Michael J. ; Gottlin, Elizabeth B.

AbstractTumor-targeting Abs can be used to initiate an antitumor immune program, which appears essential to achieve a long-term durable clinical response to cancer. We previously identified an anti–complement factor H (CFH) autoantibody associated with patients with early-stage non–small cell lung cancer. We cloned from their peripheral B cells an mAb, GT103, that specifically recognizes CFH on tumor cells. Although the underlying mechanisms are not well defined, GT103 targets a conformationally distinct CFH epitope that is created when CFH is associated with tumor cells, kills tumor cells in vitro, and has potent antitumor activity in vivo. In the effort to better understand how an Ab targeting a tumor epitope can promote an effective antitumor immune response, we used the syngeneic CMT167 lung tumor C57BL/6 mouse model, and we found that murinized GT103 (mGT103) activates complement and enhances antitumor immunity through multiple pathways. It creates a favorable tumor microenvironment by decreasing immunosuppressive regulatory T cells and myeloid-derived suppressor cells, enhances Ag-specific effector T cells, and has an additive antitumor effect with anti-PD-L1 mAb. Furthermore, the immune landscape of tumors from early-stage patients expressing the anti-CFH autoantibody is associated with an immunologically active tumor microenvironment. More broadly, our results using an mAb cloned from autoantibody-expressing B cells provides novel, to our knowledge, mechanistic insights into how a tumor-specific, complement-activating Ab can generate an immune program to kill tumor cells and inhibit tumor growth.

01 Jun 2023·Molecular cancer therapeutics

Antitumor Immune Mechanisms of the Anti-Complement Factor H Antibody GT103.

Article

Author: He, You-Wen ; Patz, Edward F ; Saxena, Ruchi ; Campa, Michael J ; Bushey, Ryan T ; Gottlin, Elizabeth B

Development of novel therapeutic antibodies that not only kill tumor cells but modulate the adaptive immune response has the potential to produce long term anticancer immunity and a durable clinical response. We previously reported the discovery of anti-complement factor H (CFH) autoantibodies in patients with lung cancer that were associated with early-stage disease and exceptional outcomes. The human mAb GT103, produced from a single CFH autoantibody-expressing B cell of a patient with lung cancer, recognizes a conformationally distinct epitope on tumor cells, kills tumor cells, and inhibits tumor growth in animal studies. Recent experiments have shown that GT103 restructures the tumor microenvironment and initiates a robust antitumoral adaptive immune response. The current study further elucidates several mechanisms by which GT103 kills tumor cells and drives the immune program. Here we show GT103 has specificity for tumor cells without binding to native soluble CFH or normal tissues. GT103 causes complement C3 split product deposition on tumor cells in vitro and in vivo, triggers antibody-dependent cellular phagocytosis, and increases translocation of the danger-associated molecular pattern molecule calreticulin to the plasma membrane. We also demonstrate that GT103 causes B-cell activation in vitro and in vivo, and that GT103 antitumor activity in vivo is B-cell dependent. The complex mechanism of GT103, a tumor-specific antibody that kills tumor cells and stimulates an immune response, supports further development of this human-derived antibody as a novel therapeutic option for patients with lung cancer.

Nature Communications

Complement factor H targeting antibody GT103 in refractory non-small cell lung cancer: a phase 1b dose escalation trial

Article

Author: Stinchcombe, Thomas E ; Antonia, Scott ; Nixon, Andrew B ; Saxena, Ruchi ; Sonpavde, Guru ; Li, Huihua ; Simon, George R ; Clarke, Jeffrey M ; Crawford, Jeffrey ; Gottlin, Elizabeth B ; Campa, Michael ; Balevic, Stephen ; Herndon, James E ; Gu, Lin ; Mamdani, Hirva ; Patz, Edward F ; He, You Wen ; Ready, Neal

AbstractGT103 is a first-in-class, fully human, IgG3 monoclonal antibody targeting complement factor H that kills tumor cells and promotes anti-cancer immunity in preclinical models. We conducted a first-in-human phase 1b study dose escalation trial of GT103 in refractory non-small cell lung cancer to assess the safety of GT103 (NCT04314089). Dose escalation was performed using a “3 + 3” schema with primary objectives of determining safety, tolerability, PK profile and maximum tolerated dose (MTD) of GT103. Secondary objectives included describing objective response rate, progression-free survival and overall survival. Dose escalation cohorts included GT103 given intravenously at 0.3, 1, 3, 10, and 15 mg/kg every 3 weeks, and 10 mg/kg every 2 weeks. Thirty one patients were enrolled across 3 institutions. Two dose-limiting adverse events were reported: grade 3 acute kidney injury (0.3 mg/kg) and grade 2 colitis (1 mg/kg). No dose-limiting toxicities were noted at the highest dose levels and the MTD was not reached. No objective responses were seen. Stable disease occurred in 9 patients (29%) and the median overall survival was 25.7 weeks (95% confidence interval [CI], 19.1–30.6). Pharmacokinetic analysis confirmed an estimated half life of 6.5 days. The recommended phase 2 dose of GT103 was 10 mg/kg every 3 weeks, however further dose optimization is needed given the absence of an MTD. The study achieved its primary objective of demonstrating safety and tolerability of GT103 in refractory NSCLC.

News (Medical) associated with GT-103

19 Dec 2023

·www.biospace.com

Infinimmune Announces Partnership with Grid Therapeutics to Conduct Deep Sequencing of B Cells for Oncology Drug Discovery

SAN FRANCISCO--(BUSINESS WIRE)-- Infinimmune, a biotechnology company pioneering new methods for antibody drug discovery and development, today announced a partnership with Grid Therapeutics (“Grid”), a clinical stage biotechnology company that focuses on human-derived antibodies, to collaborate in identifying new antibody drug candidates for non-small cell lung cancer. The partnership will use Infinimmune’s Anthrobody™ drug discovery platform. Infinimmune’s therapeutic pipeline is built on antibodies that are complete, encompassing the full binding and effector regions of both chains. These are produced by human immune systems, distinct from those derived from model organisms, display libraries, or computational algorithms. During the course of the collaboration, the two companies will jointly study the antibody repertoire from a large cohort of non-small cell lung cancer patients and control patients, who were selected on the basis of their clinical status and response to standard of care chemotherapies and immunotherapies. This will enable Grid and Infinimmune to prioritize their discovery approach using clinical information to understand differences and similarities between the antibody responses of individuals in response to lung cancer progression. “We are delighted to partner with Grid Therapeutics to study the antibody response in a carefully curated and longitudinal cohort of non-small cell lung cancer patients,” said Wyatt McDonnell, PhD, Chief Executive Officer, Infinimmune. “By leveraging our Anthrobody™ platform and Complete Human™ immunosequencing technology to identify truly human therapeutics, our collaboration with Grid Therapeutics will identify features of the antibody repertoire in non-small cell lung cancer in the pursuit of novel antibody therapeutics against existing and new targets. We are grateful to the patients who generously agreed to participate in this research.” “We are thrilled to partner with the Infinimmune team in the ongoing and transformative effort to develop novel therapeutic antibodies for cancer patients,” said Edward (Ned) F. Patz,. Jr., MD, Chief Executive Officer, Grid Therapeutics. “We aim to take full advantage of Infinimmune’s truly human antibody data, to efficiently identify better and safer therapeutics. Like Infinimmune, Grid has a platform that probes the human immune response, which we believe will be pivotal in driving the next generation of immunotherapies.” About Infinimmune Infinimmune is a biotechnology company pioneering a novel approach to antibody drug discovery and development. Founded by a world-class, multidisciplinary team of scientists and technologists, Infinimmune is reinventing antibody discovery with an end-to-end platform to deliver antibody drugs derived directly from the human immune system. These truly human antibodies are designed to drug new and existing targets with improved safety and efficacy. Infinimmune will deploy its holistic approach to build its own pipeline of drug candidates and partner with pharmaceutical companies to advance their antibody programs, fill their pipelines, and reach new patients and new indications. To learn more, visit infinimmune.com and engage with us on LinkedIn and X (Twitter). About Grid Therapeutics Grid Therapeutics is a clinical stage biotech company built on the innovative science developed by a team of researchers in Duke University School of Medicine. Located in Durham, North Carolina, Grid is currently using its unique platform to develop a pipeline of human-derived, tumor-targeted antibodies for the treatment of solid tumors. Grid’s first human antibody, GT103, discovered in early stage lung cancer patients with exceptional outcomes and isolated from single human B cells, is now in a phase 2 clinical trial (NCT05617313).

Phase 2Immunotherapy

22 Feb 2023

·www.biospace.com

Grid Therapeutics Initiates a Phase 2 Investigator-Sponsored Trial of GT103 in Combination with Merck’s Pembrolizumab in Patients with Advanced Stage Non-Small Cell Lung Cancer

DURHAM, N.C.--(BUSINESS WIRE)--Grid Therapeutics, LLC, a clinical stage biotechnology company developing human-derived antibodies, today announced the initiation of a combination Phase 2 investigator-sponsored study of its lead asset, GT103. In this clinical trial, Grid’s GT103, a novel, first-in-class antibody targeting complement factor H, will be administered in combination with KEYTRUDA® (pembrolizumab), the anti-PD-1 therapy from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. The trial will enroll patients with refractory non-small cell lung cancer (“NSCLC”) who have progressed on no more than two lines of systemic therapy, including prior PD-1 treatment. In this open-label, multi-center, single-arm Phase 2 clinical trial, Merck and Grid are each providing their respective drugs and funding support. This study is led by Jeff Clarke, M.D, member of the Duke Cancer Center Thoracic Clinic, Durham, NC. The study is managed by the Hoosier Cancer Research Network, a full-service contract research organization dedicated to providing efficiency and expertise in clinical trial services. “We are very excited to initiate this study to determine whether the therapy demonstrates clinical activity and tolerability observed in patients with advanced stage lung cancer in the Phase 1b study of GT103 alone,” said Dr. Clarke. “NSCLC is a difficult-to-treat cancer and patients, particularly in the relapsed/refractory setting, will benefit from novel therapeutic options to help improve disease outcomes.” About the Study The Phase 2 open-label, clinical trial of GT103 is designed to assess the safety and tolerability of GT103 in combination with Merck’s pembrolizumab, as well as anti-tumor activity, response rates and overall survival. The study will enroll subjects with refractory NSCLC. Please refer to for additional clinical trial details. About Grid Grid Therapeutics is a clinical stage biotech company built on the innovative science developed by a team of researchers in Duke University School of Medicine. Located in Durham, North Carolina, Grid is currently using its unique platform to develop a pipeline of human derived, tumor-targeted antibodies for the treatment of a solid tumors.

Phase 2Phase 1

03 Nov 2022

·www.biospace.com

Grid Therapeutics Announces Upcoming Scientific Presentation at the Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting

DURHAM, N.C.--(BUSINESS WIRE)-- Grid Therapeutics, LLC, a clinical-stage biopharmaceutical company developing human-derived antibodies derived from single B cells of cancer patients, announced today a poster presentation at the Society for Immunotherapy of Cancer’s 37th Annual Meeting (SITC 2022), to be held in Boston, Massachusetts and virtually on November 8-12, 2022. Presentation Details Title: Interim Results from a Phase IB, First-in-Human Study of a Novel Complement Factor H Inhibitor (GT103) in Patients with Refractory Non-Small Cell Lung Cancer (NSCLC) Abstract Number: 699 Presenter: Dr. Jeffrey Clarke, M.D., Duke Cancer Center Thoracic Clinic, Durham, NC. Date: Thursday, November 10, 2022, Poster Hall (Hall C) 9 a.m.– 9 p.m. EST All posters will be available to conference attendees as virtual e-posters during SITC 2022. The posters will also be available on November 10, 2022, in the News section of the Company’s website at , under Publications and Presentations. About the Study The Phase 1 open-label, dose-escalation clinical trial of GT103 is designed to assess the safety and tolerability of GT103 as a single agent. The study enrolled subjects with refractory NSCLC. Key objectives in the study include determining the recommended Phase 2 dose, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity. Please refer to for additional clinical trial details. About SITC Established in 1984, the Society for Immunotherapy of Cancer (SITC) is a nonprofit organization of medical professionals dedicated to improving cancer patient outcomes by advancing the development, science and application of cancer immunotherapy and tumor immunology. SITC is comprised of influential basic and translational scientists, practitioners, health care professionals, government leaders and industry professionals around the globe. Through educational initiatives that foster scientific exchange and collaboration among leaders in the field, SITC aims to one day make the word “cure” a reality for cancer patients everywhere. Learn more about SITC at sitcancer.org About Grid Grid Therapeutics is a clinical stage biotech company built on the innovative science developed by a team of researchers in Duke University School of Medicine. Located in Durham, North Carolina, Grid is currently using its unique platform to develop a pipeline of human derived, tumor-targeted antibodies for the treatment of a variety of cancers.

AntibodyFinancial StatementImmunotherapy

100 Deals associated with GT-103

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Recurrent Non-Small Cell Lung Cancer	Phase 1	US	Duke University	09 Jun 2020
Non-Small Cell Lung Cancer	Discovery	US	Duke University	03 Jun 2020

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


1487 (SITC2024)	Phase 2	metastatic non-small cell lung cancer	21	GT103 10mg/kg + Pembrolizumab 200mg IV	nkqeruydkn(cadgkjfusx) = 1 patient experienced grade 3 lymphocyte decrease oznvhoqmse (ybbksdtxkp ) View more	Positive	05 Nov 2024
NCT04314089 (ASCO2024) Manual	Phase 1	Advanced Lung Non-Small Cell Carcinoma \| \|	31	GT103 10mg/kg IV every 3 weeks	(pwezhcglcv) = not reached byovhwlcrf (pihozwklza ) Not Met View more	Positive	24 May 2024
NCT04314089 (ASCO2024) Manual	Phase 1	Advanced Lung Non-Small Cell Carcinoma \| \|	31	GT103 (PD-L1 positive (TPS > 1%))		Positive	24 May 2024
NCT04314089 (ASCO 12023 \| ASCO 22023) Manual	Phase 1	Non-Small Cell Lung Cancer	25	GT103	(nbzjkgxqud) = dqrwqlques kceojpgcyc (rnezxbasip )	Positive	26 May 2023
NCT04314089 (TOP 1902, SITC2022) Manual	Phase 1	Non-Small Cell Lung Cancer	21	GT103	(rudazsaiot) = uqgsqhnltc fmiyjdqywi (daaljhyirv, 40 - NE) View more	Positive	01 Nov 2022

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