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

August 15, 2022 updated by: PharmAbcine

A Phase 1b, Open-Label, Safety and Tolerability Study of TTAC-0001 in Combination With Pembrolizumab in Patients With Metastatic Triple-Negative Breast Cancer

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
11

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Liverpool, New South Wales, Australia, 2170
        • Liverpool Hospital
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Hollywood Private Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
During the first cycle (every cycle is 21 days) of treatment
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
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
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
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

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
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)]
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
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)
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
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
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
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

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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.
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
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
PharmAbcine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 3, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 18, 2020

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 26, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 22, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 24, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 25, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 17, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 15, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PMC_TTAC-0001_05

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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