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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03720431
Ethics application status
Date submitted
22/10/2018
Date registered
25/10/2018
Date last updated
17/08/2022

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
Timepoint [1] 0 0
During the first cycle (every cycle is 21 days) of treatment
Primary outcome [2] 0 0
Adverse events
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
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
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
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
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
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
Sex
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
Not applicable
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
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/01/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
26/10/2022
Actual
Sample size
Target
Accrual to date
Final
11
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/study/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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

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