PBF-1129 in Patients With NSCLC

NCT03274479 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: PBF-1129CT_03
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Phase I clinical trial in Eastern Cooperative Oncology Group (ECOG) 0-1 patients with locally advanced or metastatic NSCLC to evaluate safety and tolerability of the compound PBF-1129, an Adenosine A2b receptor antagonist. The phase I dose escalation will be conducted 3+3 method. Pharmacokinetic (PK) data will be also obtained.

Conditions

Locally Advanced or Metastatic NSCLC

Keywords

adenosine receptors; checkpoint inhibitors; immune system activator

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of PBF-1129

  The MTD evaluation will be based on the Dose-limiting Toxicity (DLT) of the treated Population, which includes all subjects who receive any dose of PBF-1129, and will include Adverse events (AEs), Serious Adverse events (SAEs), laboratory evaluations and electrocardiogram (ECG) results

  28 days

Secondary Outcomes (13)

• Time to PBF-1129 peak concentration in plasma "Tmax"

  days 1 and 29

• Time to PBF-1129 peak concentration in plasma at steady state "Tmax,ss"

  days 1 and 29

• PBF-1129 peak concentration in plasma "Cmax"

  days 1 and 29

• PBF-1129 peak concentration in plasma at steady state"Cmax,ss"

  days 1 and 29

• The area under PBF-1129 plasma concentration-time curve to infinite time "AUC(0-inf)"

  days 1 and 29

Study Arms (4)

PBF-1129_40mg

EXPERIMENTAL

Drug: PBF-1129

PBF-1129_80mg

EXPERIMENTAL

Drug: PBF-1129

PBF-1129_160mg

EXPERIMENTAL

Drug: PBF-1129

PBF-1129_320mg

EXPERIMENTAL

Drug: PBF-1129

Interventions

PBF-1129 DRUG

PBF-1129 once a day by oral administration

PBF-1129_160mg; PBF-1129_320mg; PBF-1129_40mg; PBF-1129_80mg

Eligibility Criteria

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

You may qualify if:

• Histological or cytological diagnosis of metastatic squamous or non-squamous NSCLC.
• Life expectancy greater or equal to 3 months, as determined by the investigator -Patients must have progressed on the standard therapy, including platinum based - chemotherapy. Patients with epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or ROS-1 mutations must have progressed on standard treatment options including EGFR, ALK, or ROS-1-directed therapies.
• No limits to the prior lines of treatment
• ECOG performance status of 0/1
• Measurable Disease by RECIST v1.1
• Age greater than 18 years.
• Adequate bone marrow, renal and hepatic function:
• Absolute neutrophil count (ANC) ≥ 1500 /µL
• White blood cell count (WBC) t ≥ 2.5 x 109/L (2500/µL)
• Lymphocyte count ≥ 0.5 x 109/L (500/µL)
• Platelet count ≥ 100 x 109/L (100,000/µL) without transfusion
• Hemoglobin ≥ (9.0 g/dL) - patients may be transfused to meet this criterion.
• Aspartate aminotransferase AST, alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN)
• Serum bilirubin ≤ 1.5 x ULN, with the exception of patients with known Gilbert disease: serum bilirubin level ≤ 3 x ULN
• Creatinine clearance \>60 mL/min (calculated using the Cockcroft-Gault formula) or by 24-hours urine collection

You may not qualify if:

• Participation in another clinical study with an investigational product during the last 4 weeks or 5 half-lives prior to starting on treatment.
• Symptomatic and/or untreated or actively progressing central nervous system (CNS) metastases or leptomeningeal disease. Patients with a history of treated CNS metastases are eligible, provided that all of the following criteria are met:
• The patient has not received stereotactic radiotherapy within 7 days prior to initiation of study treatment or whole-brain radiotherapy within 14 days prior to initiation of study treatment.
• The patient has no ongoing requirement for corticosteroids as therapy for CNS disease. Anti-convulsant therapy at a stable dose is permitted.
• Serious uncontrolled medical disorder or active infection that would impair the patient's ability to receive study treatment.
• Concurrent use of other anticancer approved or investigational agents is not allowed.
• Autoimmune disorder
• Prior malignancy in past 2 years or as identified in Section 7.2 of this protocol
• Active or prior documented autoimmune disease within the past 2 years. NOTE: Patients with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Patients receiving systemic steroids ≥ 10mg/day of prednisone or the equivalent
• Smoking (cigarettes, cigars or pipes) must be discontinued at least 7 days prior to initiating study drug administration; smoking cessation products (transdermal nicotine patches or chewing gum may be used.
• Pregnancy or breastfeeding, or intention of becoming pregnant during the study. Female subjects must either be of non-reproductive potential or have a negative serum pregnancy test result within 14 days prior to initiation of study treatment

Sponsors & Collaborators

• Palobiofarma SL: lead
• Ohio State University: collaborator

Study Sites (1)

Division of medical Oncology A450B Starling Loving Hall

Ohio City, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

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

Study Record Dates

• First Submitted: September 5, 2017
• First Posted: September 7, 2017
• Study Start: October 1, 2018
• Primary Completion: May 1, 2024
• Study Completion: August 1, 2024
• Last Updated: February 9, 2024

Record last verified: 2024-02

Locations

US (1)