TTAC-0001 and Pembrolizumab Phase Ib Combination Trial in Metastatic Triple-negative Breast Cancer

NCT03720431 | Unknown Phase 1 DMC

• 1 other identifier: PMC_TTAC-0001_05
• Study Type: interventional
• Target: 11
• 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 metastatic triple-negative breast cancer.

Conditions

Triple Negative Breast Cancer

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 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

• Immunogenicity

  Presence anti-drug antibody (ADA) will be listed

  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 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 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

• Overall survival

  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

Other Outcomes (10)

• Pharmacokinetic parameters - Cmax

  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

• Pharmacokinetic parameters - Cmin

  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

• Pharmacokinetic parameters - AUC0-t

  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

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:

• Female and male patients ≥18 years old
• 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.
• At least one confirmed measurable lesion by RECIST 1.1 criteria
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• 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.

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 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
• 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)

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Hollywood Private Hospital

Nedlands, Western Australia, 6009, Australia

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

olinvacimab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

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

Study Record Dates

• First Submitted: October 22, 2018
• First Posted: October 25, 2018
• Study Start: January 3, 2019
• Primary Completion: March 18, 2020
• Study Completion: October 26, 2022
• Last Updated: August 17, 2022

Record last verified: 2022-08

Locations

AU (2)