Solid Tumors
Conditions
Keywords
Metastatic, Stage III or IV, recurrent, refractory, solid tumors
Brief summary
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).
Interventions
DRUGTRX518 monotherapy
comparison of different (ascending) doses of TRX518 monotherapy
DRUGTRX518 with gemcitabine
comparison of different (ascending) doses of TRX518 in combination with gemcitabine
DRUGTRX518 with pembrolizumab
comparison of different (ascending) doses of TRX518 in combination with pembrolizumab
DRUGTRX518 with nivolumab
comparison of different (ascending) doses of TRX518 in combination with nivolumab
Sponsors
Leap Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | through 30 days post last dose | 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
| Measure | Time frame | Description |
|---|---|---|
| TRX518 peak concentration (Cmax) | various timepoints through 1 week post dose | 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 |
| Time to peak concentration (Tmax) | various timepoints through 1 week post dose | 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 |
| Area under the curve (AUC) | various timepoints through 1 week post dose | 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 |
| RECIST assessment for evidence of antitumor activity | up to 1 year | RECIST assessment to determine effects of TRX518 monotherapy and TRX518 in combination with gemcitabine, pembrolizumab or nivolumab on solid tumors. |
Countries
United States
Outcome results
None listed