Solid TumorsPhase 1NCT02628574

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

A Phase 1 study testing TRX518 monotherapy, TRX518 with gemcitabine and TRX518 with pembrolizumab in people with Solid Tumors, run by Leap Therapeutics, Inc. at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Solid Tumors
What is being tested?: TRX518 monotherapy, TRX518 with gemcitabine and TRX518 with pembrolizumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 109 participants
Where: 6 sitesUnited States
Study dates: Jan 2016to 14 Jul 2020
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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).

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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).

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

University of New Mexico Comprehensive Cancer Center
Albuquerque, New Mexico, 87131
University of Chicago
Chicago, Illinois, 60637
University Hospitals
Cleveland, Ohio, 44106
Cleveland Clinic
Cleveland, Ohio, 44195
Tennessee Oncology
Nashville, Tennessee, 37205
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232

Other trials in United States

About this study

Official title: A Phase 1 Study of TRX518 Monotherapy and TRX518 in Combination With Gemcitabine, Pembrolizumab, or Nivolumab in Adults With Advanced Solid Tumors

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
Being tested: TRX518 monotherapy, TRX518 with gemcitabine, TRX518 with pembrolizumab, TRX518 with nivolumab
Keywords: Metastatic, Stage III or IV, recurrent, refractory, solid tumors
Medical subject headings: Neoplasm Metastasis, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TRX518 monotherapyDrug
comparison of different (ascending) doses of TRX518 monotherapy
TRX518 with gemcitabineDrug
comparison of different (ascending) doses of TRX518 in combination with gemcitabine
TRX518 with pembrolizumabDrug
comparison of different (ascending) doses of TRX518 in combination with pembrolizumab
TRX518 with nivolumabDrug
comparison of different (ascending) doses of TRX518 in combination with nivolumab

Study groups in NCT02628574
Study group	Role	What they receive
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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: TRX518 with nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: through 30 days post last dose

Secondary outcomes (4)

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
Measured: various timepoints through 1 week post dose
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
Measured: various timepoints through 1 week post dose
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
Measured: various timepoints through 1 week post dose
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.
Measured: up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 201614 Jul 2020

First posted11 Dec 2015 (estimated)
Study startJan 2016
Primary completion14 Jul 2020
Study completion14 Jul 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Solid TumorsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 109 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02628574
Sponsor's protocol ID: TRX518-003
Status last verified: Jul 2025
First submitted: 1 Dec 2015
Last updated: 3 Aug 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 31036879

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm

All Solid Tumors trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1 Study of TRX518 Monotherapy and TRX518 in Combination With Gemcitabine, Pembrolizumab, or Nivolumab in Adults With Advanced Solid Tumors
ClinicalTrials.gov ID: NCT02628574
Acronym / sponsor ID: TRX518-003
Conditions: Solid Tumors
Keywords: Metastatic, Stage III or IV, recurrent, refractory, solid tumors
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 109 participants (actual)
Lead sponsor: Leap Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: Jan 2016 (actual)
Primary completion: 14 Jul 2020 (actual)
Study completion: 14 Jul 2020 (actual)
First posted: 11 Dec 2015 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study will be conducted in 5 parts (Parts A, B, C, D and E).

Monotherapy Treatment:

Combination Treatment:

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
TRX518 monotherapy (Parts A and B)	Experimental	Drug: TRX518 monotherapySubjects receive an assigned dose of TRX518 administered intravenously one time per week or one time per cycle on a 21-day cycle
TRX518 with gemcitabine (Part C)	Experimental	Drug: TRX518 with gemcitabineSubjects 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 pembrolizumab (Part D	Experimental	Drug: TRX518 with pembrolizumabSubjects 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 nivolumab (Part E)	Experimental	Drug: TRX518 with nivolumabSubjects 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

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (10 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TRX518 monotherapycomparison of different (ascending) doses of TRX518 monotherapy	Drug	TRX518 monotherapy (Parts A and B)
TRX518 with gemcitabinecomparison of different (ascending) doses of TRX518 in combination with gemcitabine	Drug	TRX518 with gemcitabine (Part C)
TRX518 with pembrolizumabcomparison of different (ascending) doses of TRX518 in combination with pembrolizumab	Drug	TRX518 with pembrolizumab (Part D
TRX518 with nivolumabcomparison of different (ascending) doses of TRX518 in combination with nivolumab	Drug	TRX518 with nivolumab (Part E)

Primary outcome

Adverse events
Time frame: 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

4 secondary outcomes

TRX518 peak concentration (Cmax)
Time frame: various timepoints through 1 week post dose
Time to peak concentration (Tmax)
Time frame: various timepoints through 1 week post dose
Area under the curve (AUC)
Time frame: various timepoints through 1 week post dose
RECIST assessment for evidence of antitumor activity
Time frame: up to 1 year

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2025.
Derived from this study: PubMed 31036879Zappasodi 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.
Individual participant dataSharing planned: No

Related trials for Solid Tumors

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Cyndi Sirard, MD study chair

Leap Therapeutics, Inc.

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TRX518 monotherapy, TRX518 with gemcitabine and TRX518 with pembrolizumab in people with Solid Tumors, run by Leap Therapeutics, Inc. at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse events (time frame: through 30 days post last dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02628574, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2025.