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.
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
Drug | Synonyms | Arms |
---|
TTAC-0001 and pembrolizumab combination | | TTAC-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
Name | Type | Description | Interventions |
---|
TTAC-0001 and pembrolizumab | Experimental | TTAC-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: | Active, not recruiting |
Lead Sponsor: | PharmAbcine |
Last Updated
May 19, 2021