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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03722342




Registration number
NCT03722342
Ethics application status
Date submitted
3/07/2018
Date registered
26/10/2018
Date last updated
25/02/2019

Titles & IDs
Public title
TTAC-0001 and Pembrolizumab Combination phase1b Trial in Recurrent Glioblastoma
Scientific title
A Phase 1b, Open-Label, Safety and Tolerability Study of TTAC-0001 in Combination With Pembrolizumab in Patients With Recurrent Glioblastoma
Secondary ID [1] 0 0
PMC_TTAC-0001_04
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recurrent Glioblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

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 the screening visit to the end of treatment visit (time of progressive disease or 2 years)
Primary outcome [3] 0 0
Immunogenicity - Presence anti-drug antibody (ADA) will be listed
Timepoint [3] 0 0
From screening visit to end of treatment visit (time of progressive disease or 2 years)
Secondary outcome [1] 0 0
Overall response rate - complete response (CR) or partial response (PR) by RANO 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 RANO 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 screening visit to end of treatment visit (time of progressive disease or 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 screening visit to date of patient's death (assessed up to 2 year after end of treatment visit)

Eligibility
Key inclusion criteria
1. Diagnosed with primary glioblastoma by histopathological examination and confirmed
recurrent glioblastoma by magnetic resonance imaging (MRI) scans after completing
standard of care (Stupp protocol) concomitant temozolomide chemotherapy with
radiotherapy (CCRT)

2. At least one confirmed measurable lesion by RANO criteria

3. Karnofsky Performance Status (KPS) =80

4. A person who satisfies the following criteria in haematologic, renal, and hepatic
function tests performed within 7 days prior to screening:

1. Haematologic 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 (ULN)

- Activated partial thromboplastin time (aPTT) = 1.5 x ULN

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

5. At least 12 weeks of expected survival time

6. 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 received prior radiotherapy within 2 weeks of start of study treatment. Patients
must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease

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 as demonstrated by urine dipstick for proteinuria =2+.
For patients with =2+ proteinuria on dipstick urinalysis, a urine protein: creatinine
(UPC) ratio will be determined, or a 24-hour urine collection will be done. Patients
with a UPC ratio <1 or a 24-hour urine protein <1 gram are eligible

18. Requiring therapeutic anticoagulation with warfarin at baseline; patients must be off
warfarin or warfarin-derivative anticoagulants for at least 7 days prior to starting
study drug; however, therapeutic or prophylactic therapy with low-molecular weight
heparin is allowed

19. Not recovered below National Cancer Institute-Common Terminology for Adverse Events
(NCI-CTCAE) grade 1 or baseline from AEs due to previous therapy (patient with = Grade
2 neuropathy or alopecia may be eligible)

20. Treatment with systemic chemotherapy, hormonal therapy, immunotherapy or biologic
therapy within 2 weeks prior to the baseline visit

21. Undergone major surgery requiring general anaesthesia or a respiratory assistance
device within 4 weeks prior to the baseline visit (within 2 weeks for video-assisted
thoracoscopic surgery [VATS] or open-and-closed [ONC] surgery)

22. Treated with other investigational drugs within 4 weeks prior to the baseline visit
for this study

23. Pregnant* or lactating females, and females/males of childbearing potential who do not
agree to a reliable and adequate method of contraception

24. A known history of severe drug hypersensitivity or hypersensitivity to a therapy
similar to the study drugs

25. Unable to participate in the trial according to the investigator's decision

26. Previous therapy with vascular endothelial growth factor (VEGF)-targeted agents
including (but not limited to) bevacizumab

27. 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

28. Has an active autoimmune disease that has required systemic treatment in past 2 years
(i.e., with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a form
of systemic treatment and is allowed

29. Known human immunodeficiency virus (HIV) infection. No HIV testing is required unless
mandated by local health authority

30. Known active hepatitis B or hepatitis C infection. No testing for hepatitis B and
hepatitis C is required unless mandated by local health authority

31. Have received a live vaccine within 30 days prior to enrollment. Seasonal flu vaccines
that do not contain live virus are permitted

32. Have had a serious or non-healing wound, ulcer, or bone fracture within 28 days prior
to enrollment

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)
VIC,WA
Recruitment hospital [1] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [2] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
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 recurrent glioblastoma.
Trial website
https://clinicaltrials.gov/show/NCT03722342
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
Seonyoung 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/NCT03722342