Unresectable Stage III or Stage IV Malignant Melanoma or Other Solid Tumor Malignancies Clinical Trial
— TRX518-001Official title:
Part A: A First-in-Human Single Ascending Dose Study of TRX518 in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma or Other Solid Tumor Malignancies Part B: A Dose-Escalation Study of Multi-dose TRX518 Monotherapy Part C: An Expansion Cohort of Multi-dose TRX518 Monotherapy at the Maximum Tolerated Dose
| Verified date | August 2019 |
| Source | Leap Therapeutics, Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
TRX518-001 is an open label, non-randomized single group assignment, Phase 1 single dose
escalation study in adults with biopsy proven unresectable Stage III or Stage IV melanoma or
other solid tumor malignancies.
Part A: The study objectives are to determine the safety, tolerability, pharmacokinetic (PK)
and pharmacodynamic (PD) profiles of TRX518 and to define the maximum tolerated dose at which
there are tolerable side effects and/or maximum PK/PD parameter changes.
Subjects will be assigned to a cohort in the order screening is completed. Dose will depend
upon the cohort in which a subject is enrolled and cohorts will be dosed consecutively by
ascending dose. Part A has been completed.
Part B: A Dose-Escalation Study of Multi-dose TRX518 Monotherapy with objectives including
characterization of the safety, tolerability, and pharmacokinetics, as well as, evaluate for
evidence of anti-tumor activity and assess TRX518 immunogenicity.
Part C: An Expansion Cohort of Multi-dose TRX518 Monotherapy at the Maximum Tolerated Dose
| Status | Completed |
| Enrollment | 10 |
| Est. completion date | September 2018 |
| Est. primary completion date | September 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria (Parts B & C): - 18 years or older - Histologically confirmed unresectable Stage III or Stage IV malignant melanoma, or other solid tumor malignancies - Failed to respond to or relapsed following standard treatment, declined or was not eligible for standard treatment. - Expected survival of at least 12 weeks. - Eastern Cooperative Oncology Group performance status score of 0 or 1 is required. - Evidence of adequate organ function by standard laboratory tests. Exclusion Criteria (Parts B & C): - Evidence of progression of central nervous system (CNS) metastases or symptomatic CNS metastases within 35 days prior to dosing. - Ocular melanoma which has not metastasized or presence of a non-solid tumor. - A history of any major surgery within 4 weeks prior to dosing. - Any history of antitumor therapy completed within 28 days prior to dosing. - Subjects with active autoimmune disease or history of known or suspected autoimmune disease, with the exception of subjects with isolated vitiligo, resolved childhood asthma/atopy, psoriasis not requiring systemic treatment and controlled thyroid disorders. - Clinically significant heart disease, defined as NYHA Class III or IV. - Any significant systemic infection requiring IV antibiotics. - Known to be human immunodeficiency virus (HIV) positive, have hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCAb) unless HCV RNA undetected/negative. - Treatment with any other anti-human GITR monoclonal antibody (mAb) or immunomodulatory therapy 42 days prior to dosing (30 days for Interleukin-2 & Interferon-a, 7 days for Topical Imiquimod). - Adverse events from prior anti-cancer therapy that have not resolved to grade =1 except for alopecia, vitiligo, or endocrinopathy managed with replacement therapy. - Use of any investigational drugs within 30 days prior to dosing. - Any condition that requires or is likely to require treatment with pharmacologic doses of systemic corticosteroids. Subjects are permitted to receive physiologic replacement of corticosteroid therapy (= 10 mg prednisone daily). |
| Country | Name | City | State |
|---|---|---|---|
| United States | Immunotherapeutics Core / Memorial Sloan Kettering Cancer Center | New York | New York |
| Lead Sponsor | Collaborator |
|---|---|
| Leap Therapeutics, Inc. | Cancer Research Institute, New York City |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Part A: Adverse Events | Any adverse change in health or side effect from the initiation of the study drug dose through completion or premature withdrawal | through 30 days post last dose | |
| Primary | Part A: TRX518 peak concentration (Cmax) | Observations of the distribution, duration of effects and chemical changes of TRX518 in the body and the effects and routes of the body's elimination of TRX518 | various timepoints through 1 week post dose | |
| Primary | Part A: Time to peak concentration (Tmax) | Observations of the distribution, duration of effects and chemical changes of TRX518 in the body and the effects and routes of the body's elimination of TRX518 | various timepoints through 1 week post dose | |
| Primary | Part A: Area under the curve (AUC) | Observations of the distribution, duration of effects and chemical changes of TRX518 in the body and the effects and routes of the body's elimination of TRX518 | various timepoints through 1 week post dose | |
| Primary | Part A: Define a maximum single dose at which there are tolerable side effects and/or maximum PK/PcD parameter changes | End of Cycle 1 (Day 28) | ||
| Primary | Parts B and C: Adverse Events | Any adverse change in health or side effect from the initiation of the study drug dose through completion or premature withdrawal | through 30 days post dose | |
| Secondary | Part A: Evaluate the effect of TRX518 on lymphoid cell subset number and function | At baseline and at various timepoints up to 6 weeks post dose | ||
| Secondary | Part A: Assess TRX518 immunogenicity | At baseline and at various timepoints up to 18 weeks post dose | ||
| Secondary | Part A: Evaluate the effect of TRX518 on long-term safety measuring vital signs, tumor status, adverse events | At Months 6, 12, 18 and 24 | ||
| Secondary | Parts B & C: TRX518 peak concentration (Cmax) | Observations of the distribution, duration of effects and chemical changes of TRX518 in the body and the effects and routes of the body's elimination of TRX518 | At each study visit from baseline up to end of treatment visit | |
| Secondary | Parts B & C: Time to peak concentration (Tmax) | Observations of the distribution, duration of effects and chemical changes of TRX518 in the body and the effects and routes of the body's elimination of TRX518 | At each study visit from baseline up to end of treatment visit | |
| Secondary | Parts B & C: Area under the curve (AUC) | Observations of the distribution, duration of effects and chemical changes of TRX518 in the body and the effects and routes of the body's elimination of TRX518 | At each study visit from baseline up to end of treatment visit | |
| Secondary | Parts B & C: Evaluate multi-dose TRX18 monotherapy for any evidence of antitumor activity (objective response rate, [ORR] progression free survival [PFS], duration of response and overall survival [OS]; RECIST v1.1 will be utilized | objective response rate [ORR], progression free survival [PFS], duration of response [DoR] and overall survival [OS]); RECIST v1.1 criteria will be utilized | Every 8 weeks while on study treatment and every 12 weeks for survival until death or lost to follow up. | |
| Secondary | Parts B & C: Evaluate the effect of multi-dose TRX518 monotherapy on lymphoid cell subset number and function | At baseline and at various timepoints up to end of treatment visit | ||
| Secondary | Parts B & C: Assess TRX518 immunogenicity | At baseline and at various timepoints up to end of treatment visit |