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

Primary Purpose

Non-small Cell Lung Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
GT103
Sponsored by
Edward Patz
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring Stage III/IV NSCLC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria;

  1. Histologically and/or cytologically confirmed advanced stage III, IV or recurrent NSCLC whose tumors have progressed on prior therapy.
  2. 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.

  3. 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.
  4. Age ≥ 18 years
  5. ECOG Performance Status 0 or 1 (see Appendix B)
  6. 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.
  7. Adequate liver function as shown by:

    • serum bilirubin ≤ 1.5x ULN
    • ALT and AST ≤ 2.5x ULN ; ≤ 5 x ULN with liver metastasis
  8. Adequate renal function: defined as creatinine clearance (estimated) ≥ 50 cc/min by Cockroft Gault or 24-hour urine (see Appendix E).
  9. 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 6.3.1.1 for a list of acceptable methods of contraception.
  10. Signed informed consent
  11. Willing and able to comply with clinic visits and study-related procedures and requirements.

Exclusion Criteria;

  1. 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).
  2. Patients currently receiving extracranial palliative radiation within 2 weeks from day 1 of study drug.
  3. 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.
  4. 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).
  5. 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
  6. Symptomatic brain or leptomeningeal metastases, including patients who continue to require glucocorticoids and/or antiseizure therapy for brain or leptomeningeal metastases.

    1. 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.
    2. 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.
  7. Presence of poorly controlled atrial fibrillation (ventricular heart rate >100 bpm) by EKG.
  8. 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 and/or pulmonary embolus who have been therapeutically anti-coagulated for at least 6 weeks are eligible.
  9. 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.
    4. A concurrent diagnosis of a separate malignancy is allowed if clinically stable and does not require tumor-directed therapy
  10. History of interstitial pneumonitis of autoimmune etiology (including immune checkpoint pneumonitis) which has been symptomatic and/or required treatment. History of radiation pneumonitis is allowed if the patient has recovered and does not currently require steroid therapy.
  11. 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
  12. Known autoimmune conditions requiring systemic immune suppressive therapy other than prednisone less than or equal to 10 mg.
  13. Known history of HIV seropositivity or known acquired immunodeficiency syndrome (AIDS).
  14. Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. See Section 6.3.1.1 for a complete list of medically acceptable birth control methods.
  15. 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.
  16. Patients unwilling to or unable to comply with the protocol.

Sites / Locations

  • Advent HealthRecruiting
  • Karmanos Cancer InstituteRecruiting
  • Duke University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GT103

Arm Description

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

Outcomes

Primary Outcome Measures

To determine the maximum tolerated dose (MTD), if any
The number and proportion of subjects at each dose level who experience a DLT
Time for the concentration of GT103 to reach half of the level administered
Recommended phase II dose (RP2D) of GT103
Recommended dose for the Phase II portion of the study

Secondary Outcome Measures

Response Rate
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.
Progression-Free Survival
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.
Overall Survival
OS is defined as the time between initiation of treatment and death.

Full Information

First Posted
March 16, 2020
Last Updated
July 19, 2023
Sponsor
Edward Patz
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1. Study Identification

Unique Protocol Identification Number
NCT04314089
Brief Title
Phase Ib First in Human Dose Escalation of GT103 in Refractory, Advanced Stage Non-Small Cell Lung Cancer (TOP 1902)
Official Title
Phase Ib First in Human Dose Escalation of GT103 in Refractory, Advanced Stage Non-Small Cell Lung Cancer (TOP 1902)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 9, 2020 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Edward Patz

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer
Keywords
Stage III/IV NSCLC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
GT103
Arm Type
Experimental
Arm Description
Participants will receive GT103 every 3 weeks. GT103 will be escalated from .3mg/kg up 10 to mg/kg or until MTD is found
Intervention Type
Drug
Intervention Name(s)
GT103
Intervention Description
intravenously (dose depending)
Primary Outcome Measure Information:
Title
To determine the maximum tolerated dose (MTD), if any
Description
The number and proportion of subjects at each dose level who experience a DLT
Time Frame
2 years
Title
Time for the concentration of GT103 to reach half of the level administered
Time Frame
2 years
Title
Recommended phase II dose (RP2D) of GT103
Description
Recommended dose for the Phase II portion of the study
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Response Rate
Description
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.
Time Frame
2 years
Title
Progression-Free Survival
Description
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.
Time Frame
2 years
Title
Overall Survival
Description
OS is defined as the time between initiation of treatment and death.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria; 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 ALT and AST ≤ 2.5x ULN ; ≤ 5 x ULN with liver metastasis Adequate renal function: defined as 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 6.3.1.1 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: 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. 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 and/or pulmonary embolus 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: Active (acute or chronic) infections requiring treatment with antibiotics. Liver disease such as cirrhosis, chronic active or persistent hepatitis B or C or HIV. Age related macular degeneration, atypical hemolytic uremia syndrome, glomerulonephritis, or known autoimmune diseases. A concurrent diagnosis of a separate malignancy is allowed if clinically stable and does not require tumor-directed therapy History of interstitial pneumonitis of autoimmune etiology (including immune checkpoint pneumonitis) which has been symptomatic and/or required treatment. History of radiation pneumonitis is allowed if the patient has recovered and does not currently require steroid therapy. 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 6.3.1.1 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
DCI Multi-Site Studies
Phone
919-681-4768
Email
DCI-MultiSiteStudies@duke.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Thoracic Study Team
Phone
919-681-4768
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Clarke, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Advent Health
City
Celebration
State/Province
Florida
ZIP/Postal Code
34747
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
George Simon, MD
Phone
407-303-4078
Email
Gerge.Simon.MD@AdventHealth.com
First Name & Middle Initial & Last Name & Degree
Ingrid Acker
Phone
407-303-4078
Email
Ingrid.Acker@AdventHealth.com
First Name & Middle Initial & Last Name & Degree
George Simon, MD
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alysa Mazur
Phone
313-576-9375
Email
mazura@karmanos.org
First Name & Middle Initial & Last Name & Degree
Hirva Mamdani, MD
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27540
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
DCI MultiSite
Email
DCI-MultiSiteStudies@duke.edu
First Name & Middle Initial & Last Name & Degree
Thoracic Study Team
Phone
919-681-4768
First Name & Middle Initial & Last Name & Degree
Jeffrey Clarke, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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