TTAC-0001 Phase II Trial With Recurrent Glioblastoma Progressed on Bevacizumab

A Multicenter, Open-Label, Phase Ⅱ Clinical Trial to Evaluate the Safety and Efficacy of TTAC-0001, a Fully Human Monoclonal Antibody in Patients With Recurrent Glioblastoma Progressed on Bevacizumab Including Therapy

This is a phase II, open-Label clinical trial to evaluate the safety and efficacy of TTAC-0001 in patients with recurrent glioblastoma who was progressed on bevacizumab including therapy.

Study Overview

• Status: Terminated
• Conditions: Recurrent Glioblastoma
• Intervention / Treatment: Drug: TTAC-0001

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital
• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford Avanced Medical Center
  • Florida
    • Orlando, Florida, United States, 32804
      • Florida Hospital Cancer Institute & Florida Hospital Orlando

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent prior to any study specific procedures, sampling or analyses.
2. Aged at least 18 years old
3. Patients must have a histologically proven diagnosis of glioblastoma/gliosarcoma
4. Patients must have previous treatment including bevacizumab
5. Patients must have a radiological diagnosis of recurrent/relapsed or progressive glioblastoma/gliosarcoma after bevacizumab including therapy according to response assessment in neuro-oncology (RANO) criteria
6. At least one confirmed measurable lesion or non measurable lesion as determined by RANO criteria
7. Patients must undergo IDH1 mutational testing on a tumor specimen before entering the study. Immunohistochemistry (IHC) is sufficient for enrollment, although DNA sequencing may also be performed as per local institutional guidelines. Patients are eligible regardless of their tumor status.
8. Karnofsky Performance Status (KPS) ≥ 70

9. A person who satisfies the following criteria in hematologic, renal, and hepatic function tests (1) Hematologic tests - Absolute neutrophil count (ANC) ≥ 1.5 x 109/L - Platelets ≥ 75 x 109/L

   - Hemoglobin ≥ 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 ULN
   • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3 x ULN (4) Renal function test
   • Creatinine clearance (CrCl) ≥ 30 mL/minute calculated by Cockcroft-Gault formula
10. Life expectancy of at least 12 weeks
11. Females of child bearing potential must have a negative pregnancy test during screening and must not be breastfeeding or intending to become pregnant during the study.
12. Male patients with female partners of child-bearing potential must be willing to use two forms of acceptable contraception, including one barrier method, during their participation in this study and for 16 weeks following the last dose of the study. Refer to section 10.5.1 Restrictions, permitted methods of contraception and definitions.

Exclusion Criteria:

1. Diagnosed with malignant tumors, except basal cell carcinoma, cutaneous squamous cell carcinoma, and noninvasive uterine cervical cancer treated within 2 years prior to receiving the first dose of treatment.
2. The following concomitant diseases:

(1) Uncontrolled hypertension (systolic blood pressure [SBP] > 150 or diastolic blood pressure [DBP] > 90 mmHg) (2) Uncontrolled seizures (3) Class III or IV heart failure according to New York Heart Association (NYHA) classification (4) Oxygen-dependent chronic disease (5) Active psychiatric disorder (schizophrenia, major depressive disorder, bipolar disorder etc.). Treated depression with ongoing antidepressant medication is not an exclusion.

3) Not recovered from AEs < National Cancer Institute -Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade 2 caused by CCRT 4) Treatment with bevacizumab including therapy 2 weeks prior to receiving the first dose of treatment.

5) Undergone major surgery requiring general anesthesia 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) 6) Treated with other investigational products within 4 weeks prior to the patient receiving the first dose of treatment.

7) A known history of severe drug hypersensitivity or hypersensitivity to a therapy similar to the study drug 8) Unable to participate in the trial according to the investigator's decision. 9) Patient not eligible for sequential MRI evaluations are not eligible for this study 10) Previous therapy with VEGF-targeted agents except bevacizumab. 11) Known active hepatitis B or hepatitis C infection 12) Has received a live vaccine within 30 days prior to enrollment. Seasonal flu vaccines that do not contain live virus are permitted.

13) Has had a serious or non-healing wound, ulcer, or bone fracture within 28 days prior to enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TTAC-0001; TTAC-0001 with dose assigned to each dose group will be administered	Drug: TTAC-0001; Investigational product (IP): TTAC-0001; Treatment groups: 3 dose groupsDose group A : TTAC-0001 16 mg/kg on D1 and D15Dose group B : TTAC-0001 20 mg/kg on D1 and D15Dose group C : TTAC-0001 24 mg/kg on D1 and D15; Cycle: 4 weeks (28 days per cycle)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	The frequency and percentage of AEs will be presented by dose goup	until time of progressive disease or 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival rate at 4 months	The rate and 2-sided 95% confidence interval of progression free survival at the 4-month	at the end of 4 months
Progression free survival rate at 6 months	The rate and 2-sided 95% confidence interval of progression free survival at the 6-month	at the end of 6 months
Progression free survival	Period from the date of the drug administration to the disease progression time point	until time of progressive disease or time point of patients' death which come first assessed up to 1 year
Overall survival	Period from the date of the drug administration to the time point of patient's death	until time point of patients' death up to 1 year
Objective response rate	complete response (CR) or partial response (PR) by RANO criteria	At every 2nd cycles until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year (every cycle is 28 days)
Disease control rate	complete response (CR), partial response (PR) or stable disease (SD) by RANO criteria	At every 2nd cycles until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year (every cycle is 28 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity	Presence anti-drug antibody (ADA)	From screening visit to end of treatment visit (time of progressive disease or 1 year)
Pharmacokinetic parameters - Cmax	Maximum concentration of drug by dose level	From screening visit to end of treatment visit (time of progressive disease or 1 year)
Pharmacokinetic parameters - Cmin	Minimum concentration of drug by dose level	From screening visit to end of treatment visit (time of progressive disease or 1 year)
Pharmacokinetic parameters - AUC0-t	Area under the curve from baseline to each timepoint by dose level	From screening visit to end of treatment visit (time of progressive disease or 1 year)
Pharmacokinetic parameters -Tmax	Time of Cmax by dose level	From screening visit to end of treatment visit (time of progressive disease or 1 year)
Pharmacokinetic parameters - CL	Clearance by dose level	From screening visit to end of treatment visit (time of progressive disease or 1 year)
Pharmacokinetic parameters - Vd	Volume of distribution by dose level	From screening visit to end of treatment visit (time of progressive disease or 1 year)
Pharmacokinetic parameters - Ke	Elimination rate constant by dose level	From screening visit to end of treatment visit (time of progressive disease or 1 year)
Pharmacokinetic parameters - T½	Half-life by dose level	From screening visit to end of treatment visit (time of progressive disease or 1 year)
Change in concentration of serum angiogenic factor or receptor	VEGF, placental growth factor [PLGF], soluble vascular endothelial growth factor receptor [sVEGFR]-2, sVEGFR-1, etc.	From screening visit to end of treatment visit (time of progressive disease or 1 year)
DCE-MRI	Blood flow parameter - iAUC, K-trans	Screening visit, on Day8 and Day 15 of cycle 1, Day 28 of every 2nd cycle (1 cycle is 28 days, up to 1 year)

Collaborators and Investigators

• Sponsor: PharmAbcine

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2019
• Primary Completion (Actual): July 15, 2022
• Study Completion (Actual): July 15, 2022

Study Registration Dates

• First Submitted: February 21, 2019
• First Submitted That Met QC Criteria: February 25, 2019
• First Posted (Actual): February 27, 2019

Study Record Updates

• Last Update Posted (Actual): August 18, 2022
• Last Update Submitted That Met QC Criteria: August 15, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence
• Other Study ID Numbers: PMC_TTAC-0001_03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No