Clinical Trials /

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

NCT03720431

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: TTAC-0001 and Pembrolizumab Phase Ib Combination Trial in Metastatic Triple-negative Breast Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: PMC_TTAC-0001_05
  • NCT ID: NCT03720431

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
TTAC-0001 and pembrolizumab combinationTTAC-0001 and pembrolizumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
TTAC-0001 and pembrolizumabExperimentalTTAC-0001 and pembrolizumab combination therapy will be administered.
  • TTAC-0001 and pembrolizumab combination

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose limiting toxicities
Time Frame:During the first cycle (every cycle is 21 days) of treatment
Safety Issue:
Description:The frequency and percentage of DLT will be presented by dose level

Secondary Outcome Measures

Measure: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)]
Safety Issue:
Description:complete response (CR) or partial response (PR) by RECIST criteria
Measure: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)
Safety Issue:
Description:complete response (CR), partial response (PR) or stable disease (SD) by RECIST criteria
Measure: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
Safety Issue:
Description:Period from the date of the drug administration to the disease progression time point
Measure: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
Safety Issue:
Description:Period from the date of the drug administration to the patient's death

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:PharmAbcine

Last Updated