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TTAC-0001 and Pembrolizumab Phase Ib Combination Trial in Metastatic Triple-negative Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03720431
Recruitment Status : Active, not recruiting
First Posted : October 25, 2018
Last Update Posted : April 14, 2020
Sponsor:
Information provided by (Responsible Party):
PharmAbcine

Brief Summary:
This is a phase 1b, open-Label clinical trial to determine the safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) of TTAC-0001 administered in combination with pembrolizumab in patients with metastatic triple-negative breast cancer.

Condition or disease Intervention/treatment Phase
Triple Negative Breast Cancer Drug: TTAC-0001 and pembrolizumab combination Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b, Open-Label, Safety and Tolerability Study of TTAC-0001 in Combination With Pembrolizumab in Patients With Metastatic Triple-Negative Breast Cancer
Actual Study Start Date : January 3, 2019
Estimated Primary Completion Date : April 30, 2020
Estimated Study Completion Date : April 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: TTAC-0001 and pembrolizumab
TTAC-0001 and pembrolizumab combination therapy will be administered.
Drug: TTAC-0001 and pembrolizumab combination
  • Investigational product (IP): TTAC-0001 and Pembrolizumab (Merck, Keytruda®)
  • Treatment groups: 3 dose levels

    • Dose level 1 (optimal starting dose): TTAC-0001 12 mg/kg on D1, D8 and D15 + Pembrolizumab 200 mg on D1
    • Dose level 2 (first escalation dose): TTAC-0001 16 mg/kg on D1, D8 and D15 + Pembrolizumab 200 mg on D1
    • Dose level 0 (de-escalation dose): TTAC-0001 8 mg/kg on D1, D8 and D15 + Pembrolizumab 200 mg on D1
  • Cycle: 3 weeks (21 days per cycle)




Primary Outcome Measures :
  1. Dose limiting toxicities [ Time Frame: During the first cycle (every cycle is 21 days) of treatment ]
    The frequency and percentage of DLT will be presented by dose level

  2. Adverse events [ Time Frame: From date of screening visit until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years ]
    The frequency and percentage of AEs will be presented by dose level

  3. Immunogenicity [ Time Frame: From date of screening visit until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years ]
    Presence anti-drug antibody (ADA) will be listed


Secondary Outcome Measures :
  1. Overall response rate [ Time Frame: At every 2nd cycles until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years (every cycle is 21 days)] ]
    complete response (CR) or partial response (PR) by RECIST criteria

  2. Disease control rate [ Time Frame: At every 2nd cycles until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years (every cycle is 21 days) ]
    complete response (CR), partial response (PR) or stable disease (SD) by RECIST criteria

  3. Progression free survival [ Time Frame: From date of screening visit until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years ]
    Period from the date of the drug administration to the disease progression time point

  4. Overall survival [ Time Frame: From date of screening visit until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years ]
    Period from the date of the drug administration to the patient's death


Other Outcome Measures:
  1. Pharmacokinetic parameters - Cmax [ Time Frame: From date of screening visit until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years ]
    Maximum concentration of drug by dose level

  2. Pharmacokinetic parameters - Cmin [ Time Frame: From date of screening visit until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years ]
    Minimum concentration of drug by dose level

  3. Pharmacokinetic parameters - AUC0-t [ Time Frame: From date of screening visit until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years ]
    Area under the curve from baseline to each timepoint by dose level

  4. Pharmacokinetic parameters - Tmax [ Time Frame: From date of screening visit until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years ]
    Time of Cmax by dose level

  5. Pharmacokinetic parameters - CL [ Time Frame: FFrom date of screening visit until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years ]
    Clearance by dose level

  6. Pharmacokinetic parameters - Vd [ Time Frame: From date of screening visit until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years ]
    Volume of distribution by dose level

  7. Pharmacokinetic parameters - Ke [ Time Frame: From date of screening visit until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years ]
    Elimination rate constant by dose level

  8. Pharmacokinetic parameters - T½ [ Time Frame: From date of screening visit until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years ]
    Half-life by dose level

  9. Change in concentration of serum angiogenic factor or receptor [ Time Frame: From date of screening visit until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years ]
    VEGF, placental growth factor [PLGF], soluble vascular endothelial growth factor receptor [sVEGFR]-2, sVEGFR-1, etc.

  10. PD-L1, VEGFR-2 expression level [ Time Frame: From date of screening visit until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years ]
    PD-L1, VEGFR-2 expression level in tumour environment such as tumour, tumour vessel and parenchymal tissue



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Female and male patients ≥18 years old
  2. Histologically proven metastatic breast carcinoma with triple negative receptor status (Estrogen receptor, Progesterone receptor and human epidermal growth factor receptor 2 [HER2] negative) by IHC and Fluorescence in situ hybridization (FISH) according to ASCO-CAP guideline3.
  3. At least one confirmed measurable lesion by RECIST 1.1 criteria
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  5. A person who satisfies the following criteria in hematologic, renal, and hepatic function tests performed within 7 days prior to screening:

(1) Hematologic tests

  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  • Platelets ≥ 100 x 109/L
  • Haemoglobin ≥ 9.0 g/dL (2) Blood coagulation tests
  • Prothrombin time (PT) ≤ 1.5 x Upper limit of normal (UNL)
  • Activated partial thromboplastin Time (aPTT) ≤ 1.5 x UNL (3) Hepatic function tests
  • Total bilirubin ≤ 1.5 x UNL
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metastasis) (4) Renal function test
  • ≤1.5 × ULN or creatinine clearance (CrCl) ≥30 mL/min for patient with creatinine levels >1.5 × institutional ULN 6) At least 12 weeks of expected life expectancy 7) The patient (or legally acceptable representative if applicable) is able and willing to provide written informed consent for the trial.

Exclusion Criteria:

  1. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. (Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) controlled by curative therapy are not excluded)
  2. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
  3. Has a history of (non-infectious) pneumonitis/interstitial lung diseases that required steroids or current pneumonitis/interstitial lung disease.
  4. Has an active infection requiring systemic therapy
  5. Uncontrolled hypertension (systolic blood pressure [SBP]> 150 or diastolic blood pressure [DBP]> 90 mmHg)
  6. Uncontrolled seizures
  7. Class III or IV heart failure by New York Heart Association (NYHA) classification
  8. Has oxygen-dependent chronic disease
  9. Active psychiatric disorder (schizophrenia, major depressive disorder, bipolar disorder etc.). Treated depression with ongoing antidepressant medication is not an exclusion
  10. History of abdominal fistula or gastrointestinal perforation within 6 months prior to start of study drug
  11. History of serious gastrointestinal haemorrhage within 6 months prior to start of study drug
  12. History of severe arterial thromboembolic event within 12 months of start of study drug
  13. Serious grade 4 venous thromboembolic event including pulmonary embolism
  14. History of hypertensive crisis or hypertensive encephalopathy
  15. History of posterior reversible encephalopathy syndrome
  16. Planned surgery within 4 weeks post last dose
  17. Moderate to severe proteinuria
  18. Requiring therapeutic anticoagulation with warfarin at baseline
  19. Not recovered below National Cancer Institute -Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade 1 or baseline from AEs due to previous therapy
  20. Treatment with systemic chemotherapy, hormonal therapy, immunotherapy or biologic therapy within 2 weeks prior to the baseline visit
  21. Has received prior radiotherapy within 2 weeks of start of study treatment.
  22. Undergone major surgery requiring general anaesthesia or a respiratory assistance device within 4 weeks prior to the baseline visit
  23. Treated with other investigational drugs within 4 weeks prior to the baseline visit for this study
  24. Female who is pregnant* or lactating and of childbearing potential who does not agree to a reliable and adequate method of contraception
  25. A known history of severe drug hypersensitivity or hypersensitivity to a therapy similar to the study drugs
  26. Unable to participate in the trial according to the investigator's decision.
  27. Previous therapy with vascular endothelial growth factor (VEGF)-targeted agents including (but not limited to) bevacizumab
  28. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher irAE

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03720431


Locations
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Australia, New South Wales
Liverpool Hospital
Liverpool, New South Wales, Australia, 2170
Australia, Western Australia
Hollywood Private Hospital
Nedlands, Western Australia, Australia, 6009
Sponsors and Collaborators
PharmAbcine
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Responsible Party: PharmAbcine
ClinicalTrials.gov Identifier: NCT03720431    
Other Study ID Numbers: PMC_TTAC-0001_05
First Posted: October 25, 2018    Key Record Dates
Last Update Posted: April 14, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents