Clinical Trials /

Phase 1 Open-label Study of TRX518 Monotherapy and TRX518 in Combination With Gemcitabine, Pembrolizumab, or Nivolumab

NCT02628574

Description:

This study will be conducted in 5 parts (Parts A, B, C, D and E). Monotherapy Treatment: Subjects ≥18 years with advanced solid tumors will be enrolled in the study. Monotherapy dose escalation will be performed in Part A. Cycle 1 data from each cohort will be evaluated for safety and dose-limiting toxicities (DLTs) prior to dose escalation. Subjects will be assigned to a cohort in the order screening is completed. Dose will depend upon the cohort in which a patient is enrolled and cohorts will be dosed consecutively by ascending dose. Once the maximum tolerated dose (MTD) or maximum administered dose (MAD) has been identified, an expanded cohort will be enrolled (Part B). Combination Treatment: Subjects ≥18 years with advanced solid tumors will be enrolled in the study. Subjects will receive TRX518 in combination with gemcitabine (Part C), pembrolizumab (Part D), or nivolumab (Part E). Dose escalation will be performed for each part (Part Cesc, Part Desc, Part Eesc) and Cycle 1 data from each cohort will be evaluated for safety and dose-limiting toxicities (DLTs) prior to dose escalation. Subjects will be assigned to a cohort in the order screening is completed. Dose will depend upon the cohort in which a patient is enrolled and cohorts will be dosed consecutively by ascending dose. Once the maximum tolerated dose (MTD) or maximum administered dose (MAD) has been identified, an expanded cohort will be enrolled (Part Cexp, Part Dexp, Part Eexp).

Related Conditions:
  • Bladder Carcinoma
  • Breast Carcinoma
  • Cervical Carcinoma
  • Colorectal Carcinoma
  • Gastric Carcinoma
  • Head and Neck Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma
  • Malignant Solid Tumor
  • Melanoma
  • Merkel Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Renal Cell Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase 1 Open-label Study of TRX518 Monotherapy and TRX518 in Combination With Gemcitabine, Pembrolizumab, or Nivolumab
  • Official Title: A Phase 1 Study of TRX518 Monotherapy and TRX518 in Combination With Gemcitabine, Pembrolizumab, or Nivolumab in Adults With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: TRX518-003
  • NCT ID: NCT02628574

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
TRX518 monotherapyTRX518 monotherapy (Parts A and B)
TRX518 with gemcitabineTRX518 with gemcitabine (Part C)
TRX518 with pembrolizumabTRX518 with pembrolizumab (Part D
TRX518 with nivolumabTRX518 with nivolumab (Part E)

Purpose

This study will be conducted in 5 parts (Parts A, B, C, D and E). Monotherapy Treatment: Subjects ≥18 years with advanced solid tumors will be enrolled in the study. Monotherapy dose escalation will be performed in Part A. Cycle 1 data from each cohort will be evaluated for safety and dose-limiting toxicities (DLTs) prior to dose escalation. Subjects will be assigned to a cohort in the order screening is completed. Dose will depend upon the cohort in which a patient is enrolled and cohorts will be dosed consecutively by ascending dose. Once the maximum tolerated dose (MTD) or maximum administered dose (MAD) has been identified, an expanded cohort will be enrolled (Part B). Combination Treatment: Subjects ≥18 years with advanced solid tumors will be enrolled in the study. Subjects will receive TRX518 in combination with gemcitabine (Part C), pembrolizumab (Part D), or nivolumab (Part E). Dose escalation will be performed for each part (Part Cesc, Part Desc, Part Eesc) and Cycle 1 data from each cohort will be evaluated for safety and dose-limiting toxicities (DLTs) prior to dose escalation. Subjects will be assigned to a cohort in the order screening is completed. Dose will depend upon the cohort in which a patient is enrolled and cohorts will be dosed consecutively by ascending dose. Once the maximum tolerated dose (MTD) or maximum administered dose (MAD) has been identified, an expanded cohort will be enrolled (Part Cexp, Part Dexp, Part Eexp).

Trial Arms

NameTypeDescriptionInterventions
TRX518 monotherapy (Parts A and B)ExperimentalSubjects receive an assigned dose of TRX518 administered intravenously one time per week or one time per cycle on a 21-day cycle
  • TRX518 monotherapy
TRX518 with gemcitabine (Part C)ExperimentalSubjects receive an assigned dose of TRX518 (dosed one time per cycle) intravenously administered in combination with gemcitabine (dosed two times per cycle) on a 21-day cycle
  • TRX518 with gemcitabine
TRX518 with pembrolizumab (Part DExperimentalSubjects receive an assigned dose of TRX518 (dosed one time per cycle) intravenously administered in combination with pembrolizumab (dosed one time per cycle) on a 21-day cycle
  • TRX518 with pembrolizumab
TRX518 with nivolumab (Part E)ExperimentalSubjects receive an assigned dose of TRX518 (dosed two times per cycle) intravenously administered in combination with nivolumab (dosed two times per cycle) on a 28-day cycle
  • TRX518 with nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Advanced Solid Malignancies: Histologically documented metastatic or locally advanced,
             incurable solid malignancy (Parts A and B); histologically documented metastatic or
             locally advanced, incurable solid malignancy for which gemcitabine is clinically
             appropriate (e.g., non-small cell lung, breast, ovarian, pancreatic, and renal
             cancer); histologically documented metastatic or locally advanced, incurable solid
             malignancy for which pembrolizumab (Part D) or nivolumab (Part E) is approved. NOTE:
             Parts D and E only: Subject has either (1) received treatment with pembrolizumab or
             nivolumab for ≥4 months with a best response of stable disease and plans to continue
             treatment with either pembrolizumab or nivolumab in accordance with package insert; or
             (2) is not currently taking, but is eligible for treatment with, pembrolizumab or
             nivolumab in accordance with the approved indications for each as referenced in the
             package insert.

          -  Expected survival of at least 12 weeks after dosing.

          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

          -  Evidence of adequate organ function by standard laboratory tests.

          -  All female subjects of child bearing age must be either surgically sterile,
             postmenopausal for at least 1 year, or using an acceptable method of contraception.
             Adequate contraception for both male and female subjects must be used from the
             beginning of the screening period until at least 8 weeks after the last dose of study
             drug.

        Exclusion Criteria:

          -  Hematologic malignancies or multiple myeloma.

          -  Known, clinically important cardiac or respiratory disease

          -  Any concomitant serious physical illness other than cancer (e.g., immune deficiency
             disease, bleeding disorder, etc.) within 1 year prior to dosing. No history of
             autoimmune disease.

          -  Active, uncontrolled infections within 7 days of study entry requiring systemic
             therapy.

          -  Evidence of progression of central nervous system (CNS) metastases or symptomatic CNS
             metastases within 30 days prior to dosing.

          -  History of known or suspected autoimmune disease with the specific exceptions of
             vitiligo, atopic dermatitis, or psoriasis not requiring systemic treatment. (Parts C,
             D and E only).

          -  Clinically-significant gastrointestinal disorders, such as perforation,
             gastrointestinal bleeding, or diverticulitis (Parts D and E only).

          -  Active autoimmune disease that has required systemic treatment in past 2 years (i.e.
             with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
             Replacement therapy (thyroxine, insulin, or physiologic corticosteroid replacement
             therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of
             systemic treatment (Parts D and E only).

          -  History of (non-infectious) pneumonitis that required steroids or current pneumonitis
             (Parts D and E only).

          -  History of interstitial lung disease (Parts D and E only).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse events
Time Frame:through 30 days post last dose
Safety Issue:
Description:Any adverse change in health or side effect from the initiation of the study drug dose TRX518 monotherapy and TRX518 in combination with gemcitabine, pembrolizumab or nivolumab through completion or premature withdrawal

Secondary Outcome Measures

Measure:TRX518 peak concentration (Cmax)
Time Frame:various timepoints through 1 week post dose
Safety Issue:
Description:Observations of the distribution, duration of effects and chemical changes of TRX518 monotherapy and TRX518 in combination with gemcitabine, pembrolizumab or nivolumab in the body and the effects and routes of the body's elimination of TRX518
Measure:Time to peak concentration (Tmax)
Time Frame:various timepoints through 1 week post dose
Safety Issue:
Description:Observations of the distribution, duration of effects and chemical changes of TRX518 monotherapy and TRX518 in combination with gemcitabine, pembrolizumab or nivolumab in the body and the effects and routes of the body's elimination of TRX518
Measure:Area under the curve (AUC)
Time Frame:various timepoints through 1 week post dose
Safety Issue:
Description:Observations of the distribution, duration of effects and chemical changes of TRX518 monotherapy and TRX518 in combination with gemcitabine, pembrolizumab or nivolumab in the body and the effects and routes of the body's elimination of TRX518
Measure:RECIST assessment for evidence of antitumor activity
Time Frame:up to 1 year
Safety Issue:
Description:RECIST assessment to determine effects of TRX518 monotherapy and TRX518 in combination with gemcitabine, pembrolizumab or nivolumab on solid tumors.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Leap Therapeutics, Inc.

Trial Keywords

  • Metastatic
  • Stage III or IV
  • recurrent
  • refractory
  • solid tumors

Last Updated

September 24, 2019