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

Solid Tumors Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT02628574
• Other study ID #: TRX518-003
• Status: Completed
• Phase: Phase 1
• Start date: January 2016
• Est. completion date: July 14, 2020

Study information

• Verified date: October 2020
• Source: Leap Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 109
• Est. completion date: July 14, 2020
• Est. primary completion date: July 14, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Drug:
• TRX518 monotherapy
comparison of different (ascending) doses of TRX518 monotherapy
• TRX518 with gemcitabine
comparison of different (ascending) doses of TRX518 in combination with gemcitabine
• TRX518 with pembrolizumab
comparison of different (ascending) doses of TRX518 in combination with pembrolizumab
• TRX518 with nivolumab
comparison of different (ascending) doses of TRX518 in combination with nivolumab

Locations

Country	Name	City	State
United States	University of New Mexico Comprehensive Cancer Center	Albuquerque	New Mexico
United States	University of Chicago	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	University Hospitals	Cleveland	Ohio
United States	Tennessee Oncology	Nashville	Tennessee
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Leap Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events	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	through 30 days post last dose
Secondary	TRX518 peak concentration (Cmax)	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	various timepoints through 1 week post dose
Secondary	Time to peak concentration (Tmax)	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	various timepoints through 1 week post dose
Secondary	Area under the curve (AUC)	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	various timepoints through 1 week post dose
Secondary	RECIST assessment for evidence of antitumor activity	RECIST assessment to determine effects of TRX518 monotherapy and TRX518 in combination with gemcitabine, pembrolizumab or nivolumab on solid tumors.	up to 1 year