GT103 in Combination With Pembrolizumab for the Treatment of Advanced or Metastatic STK11 Mutant Non-Small Cell Lung Cancer

Phase 2

Not yet recruiting

• Conditions: Advanced Lung Non-Small Cell Carcinoma; Metastatic Lung Non-Small Cell Carcinoma; Stage III Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8
• Interventions: Biological: Anti-CFH Monoclonal Antibody GT103; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Biological: Pembrolizumab

• Registration Number: NCT07017829
• Lead Sponsor: Roswell Park Cancer Institute

Brief Summary

This phase II trial tests how well GT103 in combination with pembrolizumab works in treating patients with STK11 mutant non-small cell lung cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). GT103 is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. GT103 targets the tumor cell-protein complement factor H found on some cancer cells and may provide specific anti-tumor activity that may help block the formation of growths that may become cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving GT103 in combination with pembrolizumab may kill more cancer cells and improve outcomes in patients with advanced or metastatic STK11 mutant non-small cell lung cancer.

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the 6-month (24 week) progression-free survival (PFS) rate of anti-CFH monoclonal antibody GT103 (GT103) in combination with pembrolizumab in patients with advanced/metastatic STK11 mutant non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. To evaluate secondary efficacy endpoints (i.e., investigator-assessed objective response rate, 12-month survival rate, overall survival, duration of response, and disease control rate) of GT103 in combination with pembrolizumab in patients with advanced/metastatic STK11 mutant NSCLC.

II. To evaluate the safety and tolerability of GT103 in combination with pembrolizumab in advanced/metastatic STK11 mutant NSCLC.

EXPLORATORY OBJECTIVES:

I. To evaluate the effects of GT103 in combination with pembrolizumab on the tumor microenvironment.

II. To explore study tissue and blood-based biomarkers as potential predictors of treatment efficacy.

OUTLINE:

Patients receive GT103 intravenously (IV) over 60 minutes and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO) at baseline, magnetic resonance imaging (MRI) at baseline and as clinically indicated, and computed tomography (CT) and blood sample collection throughout the study. Patients may also undergo biopsy throughout the study.

After completion of study treatment, patients are followed up every 30 days for 120 days.

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-04
• Study First Submitted QC: 2025-06-04
• Last Update Submitted: 2025-06-04
• Study First Posted: 2025-06-12
• Last Update Posted: 2025-06-12
• Study Start: 2025-12-01
• Primary Completion: 2028-12-01
• Study Completion: 2028-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

• Age ≥ 18 years.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 at the time of study treatment initiation.
• Have pathologically confirmed diagnosis of STK11 mutant NSCLC. STK11 mutation will be based on subject's local clinically accredited laboratory testing (Clinical Laboratory Improvement Amendments [CLIA]-certified) using deoxyribonucleic acid (DNA) sequencing test.
• Must have progressed on a pembrolizumab containing regimen and eligible for continuing pembrolizumab post-progression as determined by treating physician.
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L.
• Platelets ≥ 100 x 10^9/L.
• Hemoglobin ≥ 9 g/dL.
• Estimated glomerular filtration rate (GFR) (measured or calculated with Cockroft and Gault formula) > 45mL/min.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) (ALT and AST ≤ 5 x ULN is acceptable if liver metastases are present).
• Total bilirubin ≤ 1.5 x ULN. For patients with well documented Gilbert's syndrome, total bilirubin ≤ 3 x ULN with direct bilirubin within normal range.
• Troponin-I ≤ ULN and B-type natriuretic peptide test (BNP) < 200 pg/mL.
• Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (LLN) (institutional limit).
• Patients must have measurable disease as defined in Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.
• Participant agrees to provide blood samples at the start of treatment and at multiple times during the study. Participant agrees to provide tumor biopsy tissue or have adequate archival formalin-fixed paraffin-embedded (FFPE) tissue available.

Exclusion Criteria

• Receipt of anticancer chemotherapy within 4 weeks before the first administration of study drug.

• Prior radiotherapy or gamma knife within 2 weeks of study treatment for non-brain metastasis. Subjects must have recovered from all radiation related toxicities.

• Active/untreated brain metastasis. Whole brain radiation or gamma knife radiosurgery performed less than 4 weeks prior to first administration of study drug. Previously treated brain metastasis allowed as long as not requiring steroids and stable on imaging at least 4 weeks after completing radiation therapy.

• Leptomeningeal involvement regardless of treatment status.

• Tumor with oncogenic mutation based on standard of care broad genomic profiling in EGFR, ALK, ROS1, RET, MET, or NTRK genes.

• History of autoimmune disorder, with exception of patients with vitiligo or endocrine-related autoimmune conditions receiving appropriate hormonal supplementation who are eligible. Systemic use of immunosuppressant drugs such as steroids (except as hormone replacement therapy or short-course supportive medication such as chemotherapy or drug allergy, etc.), azathioprine, tacrolimus, cyclosporine, etc. within 4 weeks before the first administration of study drug.

• Currently receiving or has received systemic corticosteroids within 4 weeks prior to starting study drug for management of brain metastases, or who have not fully recovered from side effects of such treatment. Steroids for endocrine replacement or receipt of short-course of steroids during the preceding 4 week period as supportive medication such as for drug allergy, anti-emetic, etc. is allowed.

• Had major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered major surgery) resulting from a prior surgery.

• Has known immunosuppressive disease (e.g., HIV, AIDS or other immune depressing disease). Testing is not mandatory.

• Active, clinically serious infections or other serious uncontrolled medical conditions.

• Patient has known hypersensitivity to the components of the study drugs or any analogs.

• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator, including, but not limited to:

  • Myocardial infarction or arterial thromboembolic events within 6 months prior to baseline or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease.
  • History of documented congestive heart failure (New York Heart Association functional classification III or IV) within 6 months prior to baseline.
  • Uncontrolled hypertension (systolic blood pressure [SBP] > 160/diastolic blood pressure [DBP] > 100 despite medical intervention).
  • History of myocarditis of any etiology.
  • History of ventricular arrhythmias.

• Patients diagnosed with an invasive cancer within 2 years prior to starting protocol therapy with the following exceptions: non-melanoma skin cancers, in-situ cancers, and prostate cancer Gleason ≤ 6 (under surveillance or treated), early-stage node-negative estrogen receptor positive (ER+)/progesterone receptor positive (PR+) breast cancer with Oncotype Dx score < 25 not taking adjuvant hormonal therapy.

• Pregnant or nursing female participants.

• Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug.

• Unwilling or unable to follow protocol requirements.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (GT103, pembrolizumab)	Magnetic Resonance Imaging	Patients receive GT103 IV over 60 minutes and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO at baseline, MRI at baseline and as clinically indicated, and CT and blood sample collection throughout the study. Patients may also undergo biopsy throughout the study.
Treatment (GT103, pembrolizumab)	Anti-CFH Monoclonal Antibody GT103	Patients receive GT103 IV over 60 minutes and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO at baseline, MRI at baseline and as clinically indicated, and CT and blood sample collection throughout the study. Patients may also undergo biopsy throughout the study.
Treatment (GT103, pembrolizumab)	Biopsy Procedure	Patients receive GT103 IV over 60 minutes and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO at baseline, MRI at baseline and as clinically indicated, and CT and blood sample collection throughout the study. Patients may also undergo biopsy throughout the study.
Treatment (GT103, pembrolizumab)	Biospecimen Collection	Patients receive GT103 IV over 60 minutes and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO at baseline, MRI at baseline and as clinically indicated, and CT and blood sample collection throughout the study. Patients may also undergo biopsy throughout the study.
Treatment (GT103, pembrolizumab)	Computed Tomography	Patients receive GT103 IV over 60 minutes and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO at baseline, MRI at baseline and as clinically indicated, and CT and blood sample collection throughout the study. Patients may also undergo biopsy throughout the study.
Treatment (GT103, pembrolizumab)	Echocardiography Test	Patients receive GT103 IV over 60 minutes and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO at baseline, MRI at baseline and as clinically indicated, and CT and blood sample collection throughout the study. Patients may also undergo biopsy throughout the study.
Treatment (GT103, pembrolizumab)	Pembrolizumab	Patients receive GT103 IV over 60 minutes and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO at baseline, MRI at baseline and as clinically indicated, and CT and blood sample collection throughout the study. Patients may also undergo biopsy throughout the study.

Primary Outcome Measures

Name	Time	Method
Progression-free survival	Between study registration and documentation of disease progression or death, whichever is observed first, assessed up to 6 months (24 weeks)	Will be summarized using standard Kaplan-Meier methods, where estimates will be obtained with 90% confidence intervals.

Secondary Outcome Measures

Name	Time	Method
Objective response rate	Up to 4 years	Will be defined by the Response Evaluation Criteria in Solid Tumors version 1.1. Will be estimated using 90% credible regions obtained by Jeffrey's prior method.
Overall survival	Between registration and death from any cause, assessed up to 4 years	Will be assessed using standard Kaplan-Meier methods, where estimates will be obtained with 90% confidence intervals.
Duration of response	From the first documented objective response until the first documented disease progression or death due to any cause, assessed up to 4 years	Will be summarized using standard Kaplan-Meier methods, where estimates will be obtained with 90% confidence intervals.
Disease control rate	From the first dose of study drug until the first documentation of disease progression or death, assessed up to 4 years	Will be defined as the proportion of patients with a best overall response of confirmed complete response, confirmed partial response, or stable disease ≥ 12 weeks. The best response status will be summarized using frequencies and relative frequencies.
Incidence of adverse events	Up to 120 days after end of treatment	Toxicities and adverse events will be assessed per Common Terminology Criteria for Adverse Events version 5.0. Will be summarized by attribution and grade using frequencies and relative frequencies.

Trial Locations

Locations (1)

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States