TTAC-0001 and Pembrolizumab Combination phase1b Trial in Recurrent Glioblastoma

NCT03722342 | Unknown Phase 1 DMC

• 1 other identifier: PMC_TTAC-0001_04
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

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.

Conditions

Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (3)

• Dose limiting toxicities

  The frequency and percentage of DLT will be presented by dose level

  During the first cycle (every cycle is 21 days) of treatment

• Adverse events

  The frequency and percentage of AEs will be presented by dose level

  From the screening visit to the end of treatment visit (time of progressive disease or 2 years)

• Immunogenicity

  Presence anti-drug antibody (ADA) will be listed

  From screening visit to end of treatment visit (time of progressive disease or 2 years)

Secondary Outcomes (4)

• Overall response rate

  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)

• Disease control rate

  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)

• Progression free survival

  From screening visit to end of treatment visit (time of progressive disease or 2 years)

• Overall survival

  From screening visit to date of patient's death (assessed up to 2 year after end of treatment visit)

Other Outcomes (11)

• Pharmacokinetic parameters - Cmax

  From screening visit to end of treatment visit (time of progressive disease or 2 years)

• Pharmacokinetic parameters - Cmin

  From screening visit to end of treatment visit (time of progressive disease or 2 years)

• Pharmacokinetic parameters - AUC0-t

  From screening visit to end of treatment visit (time of progressive disease or 2 years)

Study Arms (1)

TTAC-0001 and pembrolizumab

EXPERIMENTAL

TTAC-0001 and pembrolizumab combination therapy will be administered.

Drug: TTAC-0001 and pembrolizumab combination

Interventions

TTAC-0001 and pembrolizumab combination DRUG

* 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)

TTAC-0001 and pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• At least one confirmed measurable lesion by RANO criteria
• Karnofsky Performance Status (KPS) ≥80
• A person who satisfies the following criteria in haematologic, renal, and hepatic function tests performed within 7 days prior to screening:
• Haematologic tests
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Haemoglobin ≥ 9.0 g/dL
• Blood coagulation tests
• Prothrombin time (PT) ≤ 1.5 x Upper limit of normal (ULN)
• Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
• 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)
• Renal function test

You may not qualify if:

• 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)
• 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
• Has a history of (non-infectious) pneumonitis/interstitial lung diseases that required steroids or current pneumonitis/interstitial lung disease
• Has an active infection requiring systemic therapy
• Uncontrolled hypertension (systolic blood pressure \[SBP\]\> 150 or diastolic blood pressure \[DBP\]\> 90 mmHg)
• Uncontrolled seizures
• Class III or IV heart failure by New York Heart Association (NYHA) classification
• Has oxygen-dependent chronic disease
• History of abdominal fistula or gastrointestinal perforation within 6 months prior to start of study drug
• History of serious gastrointestinal haemorrhage within 6 months prior to start of study drug
• History of severe arterial thromboembolic event within 12 months of start of study drug
• Serious grade 4 venous thromboembolic event including pulmonary embolism
• History of hypertensive crisis or hypertensive encephalopathy
• History of posterior reversible encephalopathy syndrome
• Planned surgery within 4 weeks post last dose

Sponsors & Collaborators

• PharmAbcine: lead

Study Sites (2)

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

olinvacimab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This was mTPI design to start with optimal dose and next dose level is selected accroding to DLT occurrance

Study Record Dates

• First Submitted: July 3, 2018
• First Posted: October 26, 2018
• Study Start: January 16, 2019
• Primary Completion: November 4, 2019
• Study Completion: September 30, 2022
• Last Updated: August 17, 2022

Record last verified: 2022-08

Locations

AU (2)