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

NCT ID: NCT02628574

Last Updated: 2025-08-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 109 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2020-07-14

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TRX518 monotherapy (Parts A and B)

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

Group Type: EXPERIMENTAL

TRX518 monotherapy

Intervention Type: DRUG

comparison of different (ascending) doses of TRX518 monotherapy

TRX518 with gemcitabine (Part C)

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

Group Type: EXPERIMENTAL

TRX518 with gemcitabine

Intervention Type: DRUG

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

TRX518 with pembrolizumab (Part D

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

Group Type: EXPERIMENTAL

TRX518 with pembrolizumab

Intervention Type: DRUG

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

TRX518 with nivolumab (Part E)

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

Group Type: EXPERIMENTAL

TRX518 with nivolumab

Intervention Type: DRUG

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

Interventions

TRX518 monotherapy

comparison of different (ascending) doses of TRX518 monotherapy

Intervention Type: DRUG

TRX518 with gemcitabine

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

Intervention Type: DRUG

TRX518 with pembrolizumab

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

Intervention Type: DRUG

TRX518 with nivolumab

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

Intervention Type: DRUG

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Leap Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cyndi Sirard, MD

Role: STUDY_CHAIR

Leap Therapeutics, Inc.

Locations

University of Chicago

Chicago, Illinois, United States

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, United States

University Hospitals

Cleveland, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Tennessee Oncology

Nashville, Tennessee, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 31036879 (View on PubMed)

Other Identifiers

TRX518-003

Identifier Type: -

Identifier Source: org_study_id