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

NCT04314089 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: Pro00104564
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Non-small Cell Lung Cancer

Keywords

Stage III/IV NSCLC

Outcome Measures

Primary Outcomes (3)

• To determine the maximum tolerated dose (MTD), if any

  The number and proportion of subjects at each dose level who experience a DLT

  2 years

• Time for the concentration of GT103 to reach half of the level administered

  2 years

• Recommended phase II dose (RP2D) of GT103

  Recommended dose for the Phase II portion of the study

  2 years

Secondary Outcomes (3)

• Response Rate

  2 years

• Progression-Free Survival

  2 years

• Overall Survival

  2 years

Study Arms (1)

GT103

EXPERIMENTAL

Participants will receive GT103 every 3 weeks. GT103 will be escalated from .3mg/kg up 10 to mg/kg or until MTD is found

Drug: GT103

Interventions

GT103 DRUG

intravenously (dose depending)

GT103

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically and/or cytologically confirmed advanced stage III, IV or recurrent NSCLC whose tumors have progressed on prior therapy.
• Prior Therapy:
• Patients must have received immunotherapy (anti-PD-1/PD-Ll) and a platinum- based chemotherapy either concomitantly or sequentially. There is no defined window of time since receiving immunotherapy. Immunotherapy does not have to be the immediate treatment prior to this protocol therapy.
• Patients with EGFR, ALK, or ROS1 alterations must have received at least one prior TKI and prior chemotherapy (at least one platinum doublet regimen).
• Stage III patients:
• If previously treated with immunotherapy participants with investigator-assessed radiographic disease progression or recurrence in less than 6 months after the last dose of immunotherapy in Stage III B/C disease post concurrent chemoradiotherapy followed by immunotherapy are eligible. Radiographic progression must be documented via pretreatment scan as compared to the prior therapy baseline scan in order for the participant to be eligible.
• Disease must be measurable by RECIST 1.1 criteria (see Appendix A). Tumor lesions in a previously irradiated area are considered measurable IF progression has been demonstrated in such lesions after radiation.
• Age ≥ 18 years
• ECOG Performance Status 0 or 1 (see Appendix B)
• Adequate bone marrow function as shown by:
• ANC ≥ 1.5 x 109
• Platelets ≥ 100 x 109/L
• Hemoglobin ≥ 9 g/dL; Erythropoietin and transfusion support is permitted. If patient is receiving supportive care, hemoglobin must be stable above or equal to 9 g/dL for at least 2 weeks prior to day 1 of study drug without blood transfusion to maintain hemoglobin level.
• Adequate liver function as shown by:
• serum bilirubin ≤ 1.5x ULN

You may not qualify if:

• Patients currently receiving anticancer therapies or who have received anticancer therapies within 2 weeks from day 1 of study drug (including investigational agents, chemotherapy, and antibody-based therapy).
• Patients currently receiving extracranial palliative radiation within 2 weeks from day 1 of study drug.
• Patients who:
• Have had a major surgery or significant traumatic injury within 4 weeks from day 1 of study drug,
• Have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or
• Are anticipated to require major surgery during the course of the study.
• Intolerance to PD-1/PD-L1 axis drug(s), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including prior therapy with anti-tumor vaccines or other immune-stimulatory anti-tumor agents. (Intolerance: Toxicity that warrant no subsequent/further PD-1/PD-L1 therapy).
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent with the following exceptions:
• Intermittent steroids (not to exceed prednisone 10 mg every day or equivalent dosing) may be used on an as-needed basis (e.g., treatment for chemotherapy- related nausea, anorexia and fatigue.)
• Patients on physiologic replacement doses of steroids due to adrenal insufficiency for any reason may remain on these medications.
• Topical, inhaled or intra-articular corticosteroids
• Symptomatic brain or leptomeningeal metastases, including patients who continue to require glucocorticoids and/or antiseizure therapy for brain or leptomeningeal metastases.
• Treated, asymptomatic metastases are permitted provided the patient has completed radiation at least 2 weeks prior to day 1 and has been off steroids for at least 2 weeks prior to day 1 of study drug.
• Stable (MRI or CT with contrast performed \>4 weeks apart), untreated brain metastases are permitted if patient does not require steroids and/or antiseizure therapy is not required.
• Presence of poorly controlled atrial fibrillation (ventricular heart rate \>100 bpm) by EKG.

Sponsors & Collaborators

• Edward Patz: lead

Study Sites (3)

Advent Health

Celebration, Florida, 34747, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Duke University Medical Center

Durham, North Carolina, 27540, United States

Location

Related Publications (1)

• Clarke JM, Simon GR, Mamdani H, Gu L, Herndon JE 2nd, Stinchcombe TE, Ready N, Crawford J, Sonpavde G, Balevic S, Nixon AB, Campa M, Gottlin EB, Li H, Saxena R, He YW, Antonia S, Patz EF Jr. Complement factor H targeting antibody GT103 in refractory non-small cell lung cancer: a phase 1b dose escalation trial. Nat Commun. 2025 Jan 2;16(1):93. doi: 10.1038/s41467-024-55092-2.

  PMID: 39747856 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Jeffrey Clarke, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: James and Alice Chen Distinguished Professor of Radiology

Study Record Dates

• First Submitted: March 16, 2020
• First Posted: March 18, 2020
• Study Start: June 9, 2020
• Primary Completion: April 11, 2024
• Study Completion: December 30, 2024
• Last Updated: June 17, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)