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Study of TST005 in Patients With Locally Advanced or Metastatic Solid Tumors

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ClinicalTrials.gov Identifier: NCT04958434
Recruitment Status : Recruiting
First Posted : July 12, 2021
Last Update Posted : November 3, 2021
Sponsor:
Information provided by (Responsible Party):
Transcenta Therapeutics

Tracking Information
First Submitted Date  ICMJE June 17, 2021
First Posted Date  ICMJE July 12, 2021
Last Update Posted Date November 3, 2021
Actual Study Start Date  ICMJE June 11, 2021
Estimated Primary Completion Date July 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 1, 2021)
  • Part A - Determine the maximum tolerated dose (MTD) or recommended Phase 2 dose(s) (RP2D) [ Time Frame: 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 [ Time Frame: Up to 90 days following last dose ]
    Characterize the safety profile of TST005 including the frequency and severity of treatment-emergent adverse events.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 1, 2021)
  • Part A - Area under Plasma concentration vs. time curve (AUC) for TST005 [ Time Frame: Up to 90 days following last dose ]
    Observe changes in AUC over time
  • Part A - Peak Plasma concentration (Cmax) for TST005 [ Time Frame: Up to 90 days following last dose ]
    Observe the maximum serum concentration
  • Part A - Time to maximum observed serum (Tmax) for TST005 [ Time Frame: 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 [ Time Frame: Up to 90 days following last dose ]
    Time for serum level to decrease by 1/2 during the terminal elimination phase
  • Immunogenicity of TST005 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 90 days following last dose ]
    Time between treatment of TST005 and death for any reason
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of TST005 in Patients With Locally Advanced or Metastatic Solid Tumors
Official Title  ICMJE A Phase 1, First in Human, Open-label, Dose Escalation and Dose Expansion Study of TST005 in Patients With Locally Advanced or Metastatic Solid Tumors
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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Part A - Q3w 3+3 design dose escalation Part B - Dose expansion of approximately 30 patients
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Locally Advanced or Metastatic Cancers
  • Metastatic Human Papillomavirus-Related Malignant Neoplasm
Intervention  ICMJE Drug: TST005
TST005 is a bifunctional human immunoglobulin G1 (IgG1) monoclonal
Study Arms  ICMJE
  • 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.
    Intervention: Drug: TST005
  • 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
    Intervention: Drug: TST005
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 1, 2021)
55
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2023
Estimated Primary Completion Date July 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Willing and able to provide signed and dated informed consent
  2. Patients with histologically or cytologically confirmed, locally advanced or metastatic solid tumors, evaluable by RECIST v1.1. (Part B includes metastatic HPV+ malignancies)
  3. Subject who has tumor progression during or after prior therapy and for whom no standard therapy exists that would confer clinical benefit.
  4. At least one measurable lesion per RECIST 1.1 (Part B only).
  5. Eastern Cooperative Oncology Group Performance Status (ECOG PS)0~1.
  6. Provide archived tumor tissue samples
  7. Adequate organ function

Exclusion Criteria:

  1. 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.
  2. Untreated or symptomatic central nervous system (CNS) metastases.
  3. Any unresolved Grade 2 or greater toxicity from previous anticancer therapy except alopecia.
  4. Active leptomeningeal disease.
  5. Active autoimmune diseases or history of autoimmune diseases that may relapse, with the following exceptions:

    • Controlled type 1 diabetes
    • Hypothyroidism (provided it is managed with hormone-replacement therapy only)
    • Controlled celiac disease
    • Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, or alopecia)
    • Any other disease that is not expected to recur in the absence of external triggering factors
  6. 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:

    • Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent)
    • Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption
    • 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)
  7. History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases, including but not limited to pulmonary fibrosis, active pneumonitis.
  8. 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.
  9. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy within 2 weeks of screening.
  10. Clinically significant bleeding within three months of the first dose.
  11. Uncontrolled hypertension, defined as systolic ≥150 mm Hg or diastolic ≥90 mm Hg maintained over time and despite antihypertensive treatment.
  12. 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)
  13. Pregnant or nursing.
  14. Known human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
  15. 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.
  16. Any other condition that, in the opinion of the Investigator, would prohibit the subject from participating in the study.
  17. 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.

  18. A history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  19. < 4 weeks after any major procedures/surgery; clinically significant unhealed wound; any unhealed ulceration in GI prior to first dose of TST005.
  20. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Tina Rahbarnia 949 233 2209 Tina.Rahbarnia@ppd.com
Contact: Meriam Djemai Zoghlache +33 761 539 165 Meriam.DjemaiZoghlache@ppd.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04958434
Other Study ID Numbers  ICMJE TST005-1001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: individual participant data (IPD) will not be shared to other researchers
Responsible Party Transcenta Therapeutics
Study Sponsor  ICMJE Transcenta Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Charlie Qi, MD Transcenta Therapeutics
PRS Account Transcenta Therapeutics
Verification Date November 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP