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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04314089
Recruitment Status : Recruiting
First Posted : March 18, 2020
Last Update Posted : May 27, 2021
Information provided by (Responsible Party):
Edward Patz, Duke University

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.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: GT103 Phase 1

Detailed Description:

This is a Phase Ib First in Human Dose Escalation of GT103 in Refractory, Advanced Stage (III/IV) and Recurrent Non-Small Cell Lung Cancer.

Patients with histologically confirmed recurrent, advanced stage of lung cancer, and there are no other standard therapies available may be eligible to participate in this study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib First in Human Dose Escalation of GT103 in Refractory, Advanced Stage Non-Small Cell Lung Cancer (TOP 1902)
Actual Study Start Date : June 9, 2020
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: GT103
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
intravenously (dose depending)

Primary Outcome Measures :
  1. To determine the maximum tolerated dose (MTD), if any [ Time Frame: 2 years ]
    The number and proportion of subjects at each dose level who experience a DLT

  2. Time for the concentration of GT103 to reach half of the level administered [ Time Frame: 2 years ]
  3. Recommended phase II dose (RP2D) of GT103 [ Time Frame: 2 years ]
    Recommended dose for the Phase II portion of the study

Secondary Outcome Measures :
  1. Response Rate [ Time Frame: 2 years ]
    Response rate is defined as the proportion of treated subjects with a complete or partial response. The response rate associated with the dose chosen to be the RP2D will also be estimated.

  2. Progression-Free Survival [ Time Frame: 2 years ]
    PFS is defined as the time between initiation of treatment and initial failure (disease progression or death). If the patient remains alive without disease progression at the time of analysis, PFS will be censored at the time of last follow-up. If the patient starts alternative anti-cancer therapy before progression, PFS will be censored at the time that the alternative treatment is initiated.

  3. Overall Survival [ Time Frame: 2 years ]
    OS is defined as the time between initiation of treatment and death.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically and/or cytologically confirmed advanced stage III, IV or recurrent NSCLC that is refractory to immunotherapy (anti-PD-1/PD-L1) and a platinum-based chemotherapy, either concomitantly or sequentially. Patients with EGFR, ALK, or ROS1 alterations must have received at least one prior TKI and prior chemotherapy (at least one platinum doublet regimen).
  • 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) 5. Adequate bone marrow function as shown by:

    • ANC ≥ 1.5 x 109 o 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
    • ALT and AST ≤ 2.5x ULN ; ≤ 5 x ULN with liver metastasis
  • Adequate renal function: defined as serum creatinine ≤1.5 x ULN OR creatinine clearance (estimated) ≥ 50 cc/min by Cockroft Gault or 24-hour urine (see Appendix E).
  • Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and prior to treatment on Cycle 1 Day 1; both men and women must be willing to use two medically accepted methods of contraception, one of them being a barrier method during the study and for 6 months after last study drug administration. See Section for a list of acceptable methods of contraception. -
  • Signed informed consent
  • Willing and able to comply with clinic visits and study-related procedures and requirements

Exclusion Criteria:

  • 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:

    1. Have had a major surgery or significant traumatic injury within 4 weeks from day 1 of study drug,
    2. Have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or
    3. 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 Tcell co-stimulation or immune checkpoint pathways, including prior therapy with anti-tumor vaccines or other immune-stimulatory anti- tumor agents.
  • Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent with the following exceptions:

    1. 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.)
    2. Patients on physiologic replacement doses of steroids due to adrenal insufficiency for any reason may remain on these medications.
    3. 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.
  • Severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, or in the opinion of the investigator any physiological state likely to cause systemic or regional hypoxemia).
  • Presence of poorly controlled atrial fibrillation (ventricular heart rate >100 bpm) by EKG.
  • Previous history of CVA, TIA, angina pectoris, acute MI or history of recent re-perfusion procedures (e.g., PTCA), pulmonary embolus or untreated deep vein thrombosis within 6 months from day 1 of study drug. NOTE: Subjects with recent deep vein thrombosis who have been therapeutically anti-coagulated for at least 6 weeks are eligible.
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study. Examples include but are not limited to:

    1. Active (acute or chronic) infections requiring treatment with antibiotics.
    2. Liver disease such as cirrhosis, chronic active or persistent hepatitis B or C or HIV.
    3. Age related macular degeneration, atypical hemolytic uremia syndrome, glomerulonephritis, or known autoimmune diseases.
  • History of interstitial pneumonitis from any cause
  • Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to day 1 of study drug
  • Known autoimmune conditions requiring systemic immune suppressive therapy other than prednisone less than or equal to 10 mg.
  • Known history of HIV seropositivity or known acquired immunodeficiency syndrome (AIDS).
  • Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. See Section for a complete list of medically acceptable birth control methods.
  • Corrected QTc interval > 480 msec. If QTc interval is > 480 msec, then 2 additional ECGs should be obtained over a brief period (e.g., within 15-20 minutes) to confirm the abnormality. The average QTc interval will be determined from the 3 ECG tracings by manual evaluation and will be used to determine if the subject will be excluded from the study. The same method of QTc determination must be used throughout the subject's participation in the trial.
  • Patients unwilling to or unable to comply with the protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04314089

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Contact: Carol Alonso 919-681-5425
Contact: Thoracic Study Team 919-681-4768

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United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27540
Contact: Carol Alonso    919-681-5425   
Contact: Thoracic Study Team    919-681-4768      
Principal Investigator: Jeffrey Clarke, MD         
Sponsors and Collaborators
Edward Patz
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Principal Investigator: Jeffrey Clarke, MD Duke University
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Responsible Party: Edward Patz, James and Alice Chen Distinguished Professor of Radiology, Duke University Identifier: NCT04314089    
Other Study ID Numbers: Pro00104564
First Posted: March 18, 2020    Key Record Dates
Last Update Posted: May 27, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Edward Patz, Duke University:
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms