Clinical Trials /

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

NCT04314089

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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)

Clinical Trial IDs

  • ORG STUDY ID: Pro00104564
  • NCT ID: NCT04314089

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
GT103GT103

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
GT103ExperimentalParticipants will receive GT103 every 3 weeks. GT103 will be escalated from .3mg/kg up 10 to mg/kg or until MTD is found
  • GT103

Eligibility Criteria

        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 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:

               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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To determine the maximum tolerated dose (MTD), if any
Time Frame:2 years
Safety Issue:
Description:The number and proportion of subjects at each dose level who experience a DLT

Secondary Outcome Measures

Measure:Response Rate
Time Frame:2 years
Safety Issue:
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.
Measure:Progression-Free Survival
Time Frame:2 years
Safety Issue:
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.
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:OS is defined as the time between initiation of treatment and death.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Edward Patz

Trial Keywords

  • Stage III/IV NSCLC

Last Updated

March 17, 2020