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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03720431




Registration number
NCT03720431
Ethics application status
Date submitted
22/10/2018
Date registered
25/10/2018
Date last updated
21/01/2019

Titles & IDs
Public title
TTAC-0001 and Pembrolizumab Phase Ib Combination Trial in Metastatic Triple-negative Breast Cancer
Scientific 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
Secondary ID [1] 0 0
PMC_TTAC-0001_05
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Triple Negative Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TTAC-0001 and pembrolizumab combination

Experimental: TTAC-0001 and pembrolizumab - TTAC-0001 and pembrolizumab combination therapy will be administered.


Treatment: Drugs: 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)

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose limiting toxicities - The frequency and percentage of DLT will be presented by dose level
Timepoint [1] 0 0
During the first cycle (every cycle is 21 days) of treatment
Primary outcome [2] 0 0
Adverse events - The frequency and percentage of AEs will be presented by dose level
Timepoint [2] 0 0
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
Primary outcome [3] 0 0
Immunogenicity - Presence anti-drug antibody (ADA) will be listed
Timepoint [3] 0 0
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 [1] 0 0
Overall response rate - complete response (CR) or partial response (PR) by RECIST criteria
Timepoint [1] 0 0
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)]
Secondary outcome [2] 0 0
Disease control rate - complete response (CR), partial response (PR) or stable disease (SD) by RECIST criteria
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Progression free survival - Period from the date of the drug administration to the disease progression time point
Timepoint [3] 0 0
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 [4] 0 0
Overall survival - Period from the date of the drug administration to the patient's death
Timepoint [4] 0 0
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

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
Hollywood Private Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
PharmAbcine
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03720431
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Seon Young Lee, MPH
Address 0 0
Country 0 0
Phone 0 0
+82-10-4360-2257
Fax 0 0
Email 0 0
sylee@pharmabcine.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03720431