GT103 / Duke University, Grid Therap - LARVOL DELTA

A Phase II study of GT103 in combination with pembrolizumab in refractory, metastatic non-small cell lung cancer. (PubMed, Cancer) - "Combination of GT103 with pembrolizumab was well tolerated with no new safety signals. A subset of patients experienced durable responses and disease control despite prior exposure to ICI."

Journal • P2 data • Fatigue • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Solid Tumor

GT103 in Combination With Pembrolizumab for the Treatment of Advanced or Metastatic STK11 Mutant Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=28 | Recruiting | Sponsor: Roswell Park Cancer Institute | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

HCRN LUN21-497: Study of GT103 in Combination With Pembrolizumab in Refractory, Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=21 | Terminated | Sponsor: Jeffrey Clarke | Trial completion date: Jan 2028 ➔ Jun 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jan 2026 ➔ Jun 2025; Study did not meet the criteria for continuation after interim analysis

Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • KRAS • MET • ROS1

Phase Ib First in Human Dose Escalation of GT103 in Refractory, Advanced Stage Non-Small Cell Lung Cancer (TOP 1902) (clinicaltrials.gov) - P1 | N=31 | Completed | Sponsor: Edward Patz | Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1

GT103 in Combination With Pembrolizumab for the Treatment of Advanced or Metastatic STK11 Mutant Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=28 | Not yet recruiting | Sponsor: Roswell Park Cancer Institute

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A tumor-binding antibody with cross-reactivity to viral antigens. (PubMed, Cancer Immunol Immunother) - "These findings suggest that memory B cells against a viral target could have affinity matured to produce an antibody that recognizes a similar epitope on tumor cells and exhibits antitumor properties."

Journal • Infectious Disease • Lung Cancer • Measles • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Results from a phase II study of GT103 in combination with pembrolizumab in refractory, metastatic non-small cell lung cancer (SITC 2024) - P2 | "Ethics Approval The institutional review board of the participating centers approved the study, and this trial was conducted in accordance with Good Clinical Practice guidelines and the provisions of the Declaration of Helsinki. Patients were required to provide informed consent before any study-related procedures."

Combination therapy • IO biomarker • Late-breaking abstract • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Study of GT103 in Combination With Pembrolizumab in Refractory, Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=21 | Active, not recruiting | Sponsor: Jeffrey Clarke | Suspended ➔ Active, not recruiting | N=50 ➔ 21 | Trial completion date: Jan 2030 ➔ Jan 2028 | Trial primary completion date: Jan 2029 ➔ Jan 2026

Combination therapy • Enrollment change • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • KRAS • MET • ROS1

Phase Ib First in Human Dose Escalation of GT103 in Refractory, Advanced Stage Non-Small Cell Lung Cancer (TOP 1902) (clinicaltrials.gov) - P1 | N=31 | Active, not recruiting | Sponsor: Edward Patz | Trial primary completion date: Dec 2024 ➔ Apr 2024

Metastases • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1

Phase Ib First in Human Dose Escalation of GT103 in Refractory, Advanced Stage Non-Small Cell Lung Cancer (TOP 1902) (clinicaltrials.gov) - P1 | N=31 | Active, not recruiting | Sponsor: Edward Patz | Trial completion date: Dec 2024 ➔ Mar 2025 | Trial primary completion date: Jun 2024 ➔ Dec 2024

Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1

Safety and efficacy of complement factor H (CFH) inhibitor GT103 in advanced non-small cell lung cancer (NSCLC): Results of a phase Ib first in human dose escalation study. (ASCO 2024) - P1 | "GT103 was well tolerated across all dose levels. The RP2D of 10mg/kg IV every 3 weeks was selected, although PK modeling will be performed to optimize the dosing schedule. Encouraging anti-tumor activity was seen in heavily pretreated pts with advanced NSCLC with a subset of patients experiencing stable disease lasting for longer than 6 months."

Clinical • IO biomarker • Metastases • P1 data • Acute Kidney Injury • Anemia • Fatigue • Hematological Disorders • Lung Cancer • Nephrology • Non Small Cell Lung Cancer • Oncology • Renal Disease • Solid Tumor • EGFR • FCGR2A • KRAS • PD-L1

Targeting complement factor H renders STK11-mutant lung adenocarcinoma sensitive to anti-PD-1 therapy in mice (AACR 2024) - P2 | "GT103 is a therapeutic antibody that binds tumor cell-attached CFH, causes complement activation, kills tumor cells, initiates a shift from a pro- to an anti-tumor immune microenvironment, and is currently being evaluated in a Phase 1b-2 clinical trial in combination with pembrolizumab (NCT05617313). Our results support a role of tumor-derived C3 in suppressing CD8 T-cell immunity and in driving ICI resistance and that the addition of GT103 renders STK11-KO tumors sensitive to anti-PD-1 in mice. These studies establish rationale for evaluating this combination in patients with STK11-mutant LUAD."

IO biomarker • Preclinical • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • KRAS • STK11

Promotion of an Antitumor Immune Program by a Tumor-specific, Complement-activating Antibody. (PubMed, J Immunol) - "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. 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."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Study of GT103 in Combination With Pembrolizumab in Refractory, Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=50 | Suspended | Sponsor: Jeffrey Clarke | Trial primary completion date: Jan 2024 ➔ Jan 2029

Combination therapy • Metastases • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • KRAS • MET • ROS1

Study of GT103 in Combination With Pembrolizumab in Refractory, Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=50 | Suspended | Sponsor: Jeffrey Clarke | Recruiting ➔ Suspended

Combination therapy • Metastases • Trial suspension • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • KRAS • MET • ROS1

Phase Ib First in Human Dose Escalation of GT103 in Refractory, Advanced Stage Non-Small Cell Lung Cancer (TOP 1902) (clinicaltrials.gov) - P1 | N=31 | Active, not recruiting | Sponsor: Edward Patz | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2024 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Jun 2024

Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1

Phase Ib First in Human Dose Escalation of GT103 in Refractory, Advanced Stage Non-Small Cell Lung Cancer (TOP 1902) (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Edward Patz | Trial completion date: Jun 2023 ➔ Jun 2024 | Trial primary completion date: Jun 2023 ➔ Dec 2023

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1

Clinico-laboratory Profile and Outcomes of Megaloblastic Anemia presenting as Severe Pyrexial Illness mimicking Tropical Infection. (PubMed, J Assoc Physicians India) - "Around 24 cases of megaloblastic anemia presenting with high-grade fever were included, with 14 (58.3%) males, mean duration of fever 7.7 days (4-18 days), and 09 (37.5%) having temperature >103°F...The study population was divided into those with temperature ≥103°F, and temperature <103°F it was seen that there was a significant association (p < 0.05) with leucocyte count of ≤3000/cumm, and MCV ≥110 fL, in patients with temperature ≥103°F Megaloblastic anemia should be considered in the differentials of a patient presenting with a febrile illness with no clinical localization and a negative initial fever workup. Early identification and prompt therapy of this easily treatable disorder are very essential."

Journal • Anemia • Hematological Disorders • Hepatology • Infectious Disease

Results from a first-in-human phase 1B study of a complement factor H inhibitor (GT103) in patients with non-small cell lung cancer (NSCLC). (ASCO 2023) - P1 | "A separate phase 2 study of combination GT103 with pembrolizumab is planned for patients with refractory NSCLC. GT103 is well tolerated in heavily pretreated advanced NSCLC population. Early clinical activity has been demonstrated to date with stable disease seen in 24% of patients. Updated clinical results and correlative data will be presented."

Clinical • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Antitumor Immune Mechanisms of the Anti-Complement Factor H Antibody GT103. (PubMed, Mol Cancer Ther) - "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."

Journal • Lung Cancer • Oncology • Solid Tumor • CALR

Study of GT103 in Combination With Pembrolizumab in Refractory, Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Jeffrey Clarke | Not yet recruiting ➔ Recruiting | Initiation date: Jun 2023 ➔ Feb 2023

Combination therapy • Enrollment open • Metastases • Trial initiation date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • MET • ROS1

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 (Businesswire) - "Grid Therapeutics... 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."

Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Study of GT103 in Combination With Pembrolizumab in Refractory, Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=50 | Not yet recruiting | Sponsor: Jeffrey Clarke | Initiation date: Dec 2022 ➔ Jun 2023

Combination therapy • Metastases • Trial initiation date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • MET • ROS1

Phase Ib First in Human Dose Escalation of GT103 in Refractory, Advanced Stage Non-Small Cell Lung Cancer (TOP 1902) (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Edward Patz | Suspended ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1

Study of GT103 in Combination With Pembrolizumab in Refractory, Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=50 | Not yet recruiting | Sponsor: Jeffrey Clarke

Combination therapy • New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • MET • ROS1