Triple Negative Breast CancerPhase 1NCT03720431
TTAC-0001 and Pembrolizumab Phase Ib Combination Trial in Metastatic Triple-negative Breast Cancer
A Phase 1 study testing TTAC-0001 and pembrolizumab combination in people with Triple Negative Breast Cancer, run by PharmAbcine at 2 sites in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Triple Negative Breast Cancer
- What is being tested?
- TTAC-0001 and pembrolizumab combination
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 2 sitesAustralia
- Study dates
- 3 Jan 2019to 26 Oct 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female and male patients ≥18 years old
- 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.
- At least one confirmed measurable lesion by RECIST 1.1 criteria
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- A person who satisfies the following criteria in hematologic, renal, and hepatic function tests performed within 7 days prior to screening:
- Hematologic tests
Show all 14Show fewer
- 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.
Who cannot join
- 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)
- 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
- Has a history of (non-infectious) pneumonitis/interstitial lung diseases that required steroids or current pneumonitis/interstitial lung disease.
- Has an active infection requiring systemic therapy
- Uncontrolled hypertension (systolic blood pressure [SBP]> 150 or diastolic blood pressure [DBP]> 90 mmHg)
- Uncontrolled seizures
Show all 28Show fewer
- Class III or IV heart failure by New York Heart Association (NYHA) classification
- Has oxygen-dependent chronic disease
- Active psychiatric disorder (schizophrenia, major depressive disorder, bipolar disorder etc.). Treated depression with ongoing antidepressant medication is not an exclusion
- History of abdominal fistula or gastrointestinal perforation within 6 months prior to start of study drug
- History of serious gastrointestinal haemorrhage within 6 months prior to start of study drug
- History of severe arterial thromboembolic event within 12 months of start of study drug
- Serious grade 4 venous thromboembolic event including pulmonary embolism
- History of hypertensive crisis or hypertensive encephalopathy
- History of posterior reversible encephalopathy syndrome
- Planned surgery within 4 weeks post last dose
- Moderate to severe proteinuria
- Requiring therapeutic anticoagulation with warfarin at baseline
- Not recovered below National Cancer Institute -Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade 1 or baseline from AEs due to previous therapy
- Treatment with systemic chemotherapy, hormonal therapy, immunotherapy or biologic therapy within 2 weeks prior to the baseline visit
- Has received prior radiotherapy within 2 weeks of start of study treatment.
- Undergone major surgery requiring general anaesthesia or a respiratory assistance device within 4 weeks prior to the baseline visit
- Treated with other investigational drugs within 4 weeks prior to the baseline visit for this study
- Female who is pregnant* or lactating and of childbearing potential who does not agree to a reliable and adequate method of contraception
- A known history of severe drug hypersensitivity or hypersensitivity to a therapy similar to the study drugs
- Unable to participate in the trial according to the investigator's decision.
- Previous therapy with vascular endothelial growth factor (VEGF)-targeted agents including (but not limited to) bevacizumab
- 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
Trial locations and contacts
2 sites in 1 country.
Australia2 sites
Liverpool Hospital
Liverpool, New South Wales, 2170
Hollywood Private Hospital
Nedlands, Western Australia, 6009
About this study
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
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.
- Conditions
- Triple Negative Breast Cancer
- Being tested
- TTAC-0001 and pembrolizumab combination
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TTAC-0001 and pembrolizumab combinationDrug
- 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)
| Study group | Role | What they receive |
|---|---|---|
| TTAC-0001 and pembrolizumab | Experimental | TTAC-0001 and pembrolizumab combination therapy will be administered. Receives: Drug: TTAC-0001 and pembrolizumab combination |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicities
The frequency and percentage of DLT will be presented by dose level
Measured: During the first cycle (every cycle is 21 days) of treatment
Adverse events
The frequency and percentage of AEs will be presented by dose level
Measured: 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
Presence anti-drug antibody (ADA) will be listed
Measured: 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 outcomes (4)
Overall response rate
complete response (CR) or partial response (PR) by RECIST criteria
Measured: 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
complete response (CR), partial response (PR) or stable disease (SD) by RECIST criteria
Measured: 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
Period from the date of the drug administration to the disease progression time point
Measured: 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
Period from the date of the drug administration to the patient's death
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2018
- Study start3 Jan 2019
- Primary completion18 Mar 2020
- Study completion26 Oct 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Triple Negative Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- PharmAbcine
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03720431
- Sponsor's protocol ID
- PMC_TTAC-0001_05
- Status last verified
- Aug 2022
- First submitted
- 22 Oct 2018
- Last updated
- 17 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03720431
- Acronym / sponsor ID
- PMC_TTAC-0001_05
- Conditions
- Triple Negative Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 11 participants (actual)
- Lead sponsor
- PharmAbcineIndustry (pharma, biotech, devices)
- Study start
- 3 Jan 2019 (actual)
- Primary completion
- 18 Mar 2020 (actual)
- Study completion
- 26 Oct 2022 (estimated)
- First posted
- 25 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TTAC-0001 and pembrolizumab | Experimental | Drug: TTAC-0001 and pembrolizumab combinationTTAC-0001 and pembrolizumab combination therapy will be administered. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Female and male patients ≥18 years old
- 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.
- At least one confirmed measurable lesion by RECIST 1.1 criteria
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- A person who satisfies the following criteria in hematologic, renal, and hepatic function tests performed within 7 days prior to screening:
Key exclusion criteria (28 listed)
- 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)
- 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
- Has a history of (non-infectious) pneumonitis/interstitial lung diseases that required steroids or current pneumonitis/interstitial lung disease.
- Has an active infection requiring systemic therapy
- Uncontrolled hypertension (systolic blood pressure [SBP]> 150 or diastolic blood pressure [DBP]> 90 mmHg)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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) | Drug | TTAC-0001 and pembrolizumab |
Primary outcome
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
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
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
4 secondary outcomes
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)]
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)
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
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TTAC-0001 and pembrolizumab combination in people with Triple Negative Breast Cancer, run by PharmAbcine at 2 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicities (time frame: During the first cycle (every cycle is 21 days) of treatment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2022.