Study of TST005 in Patients With Locally Advanced or Metastatic Solid Tumors
Study Details
Study Description
Brief Summary
This is an open label Phase 1, first-in-human (FIH) study of TST005, a bi-specific antibody consisting of a PD-L1 monoclonal antibody (mAb) and a transforming growth factor beta (TGF-β) trap in subjects with locally advanced or metastatic cancers
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
The study has 2 parts. Part A is a dose escalation portion where the patients will be doses every three weeks following an accelerated 3+3 design. This portion will enroll approximately 25 patients with locally advanced or metastatic cancers.
Part B is an expansion portion where approximately 30 additional patients will be dosed at the recommended dose level every 3 weeks. This part will include patients with locally advanced or metastatic HPV related malignancies.
The trial will last approximately 2 years, with assessments including safety labs, ECGs, PKs and PDs and CT/MRI tumor assessments, based on the Q3W dosing schedule.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part A - Dose Escalation Dosed every 3 weeks IV with TST005, starting dose is 1 mg/kg, and 5 dose levels will be tested. |
Drug: TST005
TST005 is a bifunctional human immunoglobulin G1 (IgG1) monoclonal
|
| Experimental: Part B - Dose Expansion Participants with any kind of advanced or HPV metastatic solid tumors dosed Q3W with the Part A Q3W recommended dose of TST005 |
Drug: TST005
TST005 is a bifunctional human immunoglobulin G1 (IgG1) monoclonal
|
Outcome Measures
Primary Outcome Measures
- Part A - Determine the maximum tolerated dose (MTD) or recommended Phase 2 dose(s) (RP2D) [Up to 90 days following last dose]
As measured by the number of participants experiencing a dose limiting toxicity (DLT) in each dosing cohort
- Part B - Patient safety as characterized by frequency and severity of adverse events [Up to 90 days following last dose]
Characterize the safety profile of TST005 including the frequency and severity of treatment-emergent adverse events.
Secondary Outcome Measures
- Part A - Area under Plasma concentration vs. time curve (AUC) for TST005 [Up to 90 days following last dose]
Observe changes in AUC over time
- Part A - Peak Plasma concentration (Cmax) for TST005 [Up to 90 days following last dose]
Observe the maximum serum concentration
- Part A - Time to maximum observed serum (Tmax) for TST005 [Up to 90 days following last dose]
Tmax is the time in hours / days for TST005 to reach the maximum concentration after administration
- Part A - Terminal half-life of TST005 [Up to 90 days following last dose]
Time for serum level to decrease by 1/2 during the terminal elimination phase
- Immunogenicity of TST005 [Up to 90 days following last dose]
To determine if the formation of Anti-drug antibodies (ADA) or neutralizing antibodies (NAb) against TST005 are observed
- Part B - Assess the Objective response rate (ORR) of TST005 [Up to 90 days following last dose]
as measured by RECIST v 1.1 and iRECIST
- Part B - Assess the Disease Control rate (DCR) of TST005 [Up to 90 days following last dose]
Percentage of patients that exhibit stable disease (SD), + partial response (PR), + complete response (CR)
- Part B - Assess the Duration of Response of TST005 [Up to 90 days following last dose]
Measured by the time a patient shows response
- Part B - Assess the Time to Response (TTR) of TST005 [Up to 90 days following last dose]
Measured by the average time patients show a response to TST005
- Part B - Assess the Progression -free Survival (PFS) of TST005 [Up to 90 days following last dose]
Measured by the average time before patients show signs of disease progression after receiving TST005
- Part B - Assess the Overall Survival (OS) of TST005 [Up to 90 days following last dose]
Time between treatment of TST005 and death for any reason
Eligibility Criteria
Criteria
Inclusion Criteria:
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Willing and able to provide signed and dated informed consent
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Patients with histologically or cytologically confirmed, locally advanced or metastatic solid tumors, evaluable by RECIST v1.1. (Part B includes metastatic HPV+ malignancies)
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Subject who has tumor progression during or after prior therapy and for whom no standard therapy exists that would confer clinical benefit.
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At least one measurable lesion per RECIST 1.1 (Part B only).
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Eastern Cooperative Oncology Group Performance Status (ECOG PS)0~1.
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Provide archived tumor tissue samples
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Adequate organ function
Exclusion Criteria:
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Concurrent malignancy within 3 years prior to entry other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, prostate cancer not requiring treatment (with or without resection), ductal carcinoma in situ of the breast, or ≤ T1 urothelial carcinoma.
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Untreated or symptomatic central nervous system (CNS) metastases.
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Any unresolved Grade 2 or greater toxicity from previous anticancer therapy except alopecia.
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Active leptomeningeal disease.
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Active autoimmune diseases or history of autoimmune diseases that may relapse, with the following exceptions:
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Controlled type 1 diabetes
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Hypothyroidism (provided it is managed with hormone-replacement therapy only)
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Controlled celiac disease
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Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, or alopecia)
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Any other disease that is not expected to recur in the absence of external triggering factors
- Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before the first dose of investigational product, with the following exceptions:
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Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent)
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Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption
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Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, for contrast dye allergy) or for the treatment of a non-autoimmune condition (eg, delayed-type hypersensitivity reaction caused by contact allergen)
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History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases, including but not limited to pulmonary fibrosis, active pneumonitis.
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Severe cardiovascular disease, including cerebrovascular accident, transient ischemic attack, myocardial infarction, or unstable angina, New York Heart Association class III or IV heart failure or uncontrolled arrhythmia within 6 months of first dose.
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Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy within 2 weeks of screening.
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Clinically significant bleeding within three months of the first dose.
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Uncontrolled hypertension, defined as systolic ≥150 mm Hg or diastolic ≥90 mm Hg maintained over time and despite antihypertensive treatment.
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Patients with QTcF > 480 ms on screening ECG or with a history of additional risk factors for TdP (e.g., heart failure, hypokalemia，family history of Long QT Syndrome)
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Pregnant or nursing.
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Known human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
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A serious nonmalignant disease (e.g., psychiatric, substance abuse, uncontrolled intercurrent illness, etc.) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.
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Any other condition that, in the opinion of the Investigator, would prohibit the subject from participating in the study.
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Active autoimmune disease requiring systemic therapy in the last 2 years prior to the first dose (i.e., with use of disease modifying agents, systemic corticosteroids or immunosuppressive drug).
• Subjects with Type 1 diabetes mellitus (TD1M), hypothyroidism requiring only hormone replacement, or skin disorders not requiring systemic treatment are permitted to enroll.
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A history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
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< 4 weeks after any major procedures/surgery; clinically significant unhealed wound; any unhealed ulceration in GI prior to first dose of TST005.
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History of severe immune-related adverse effects from checkpoint inhibitor (CPI) therapy (NCI CTCAE Grade 3 or 4) with the exception of endocrinopathy managed with replacement therapy or subjects who discontinued CPI therapy for CPI-associated toxicity or intolerability.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Gabrail Cancer Center | Canton | Ohio | United States | 44718 |
| 2 | Mary Crowley Cancer Research | Dallas | Texas | United States | 75230 |
| 3 | NEXT Oncology | San Antonio | Texas | United States | 78229 |
Sponsors and Collaborators
- Transcenta Therapeutics
Investigators
- Study Director: Charlie Qi, MD, Transcenta Therapeutics
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TST005-1001