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

NCT02628574 | Completed Phase 1 FDA Drug

• 1 other identifier: TRX518-003
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 6

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).

Conditions

Solid Tumors

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• TRX518 peak concentration (Cmax)

  various timepoints through 1 week post dose

• Time to peak concentration (Tmax)

  various timepoints through 1 week post dose

• Area under the curve (AUC)

  various timepoints through 1 week post dose

• RECIST assessment for evidence of antitumor activity

  up to 1 year

Study Arms (4)

TRX518 monotherapy (Parts A and B)

EXPERIMENTAL

Subjects receive an assigned dose of TRX518 administered intravenously one time per week or one time per cycle on a 21-day cycle

Drug: TRX518 monotherapy

TRX518 with gemcitabine (Part C)

EXPERIMENTAL

Subjects 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

Drug: TRX518 with gemcitabine

TRX518 with pembrolizumab (Part D

EXPERIMENTAL

Subjects 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

Drug: TRX518 with pembrolizumab

TRX518 with nivolumab (Part E)

EXPERIMENTAL

Subjects 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

Drug: TRX518 with nivolumab

Interventions

TRX518 monotherapy DRUG

comparison of different (ascending) doses of TRX518 monotherapy

TRX518 monotherapy (Parts A and B)

TRX518 with gemcitabine DRUG

comparison of different (ascending) doses of TRX518 in combination with gemcitabine

TRX518 with gemcitabine (Part C)

TRX518 with pembrolizumab DRUG

comparison of different (ascending) doses of TRX518 in combination with pembrolizumab

TRX518 with pembrolizumab (Part D

TRX518 with nivolumab DRUG

comparison of different (ascending) doses of TRX518 in combination with nivolumab

TRX518 with nivolumab (Part E)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Leap Therapeutics, Inc.: lead

Study Sites (6)

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87131, United States

Location

University Hospitals

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37205, United States

Location

Related Publications (1)

• Zappasodi R, Sirard C, Li Y, Budhu S, Abu-Akeel M, Liu C, Yang X, Zhong H, Newman W, Qi J, Wong P, Schaer D, Koon H, Velcheti V, Hellmann MD, Postow MA, Callahan MK, Wolchok JD, Merghoub T. Rational design of anti-GITR-based combination immunotherapy. Nat Med. 2019 May;25(5):759-766. doi: 10.1038/s41591-019-0420-8. Epub 2019 Apr 29.

  PMID: 31036879 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Recurrence

Interventions

Gemcitabine; pembrolizumab; Nivolumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Cyndi Sirard, MD

  Leap Therapeutics, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2015
• First Posted: December 11, 2015
• Study Start: January 1, 2016
• Primary Completion: July 14, 2020
• Study Completion: July 14, 2020
• Last Updated: August 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)