PBF-1129 in Patients With NSCLC

Palobiofarma

Status and phase: Active, not recruiting; Phase 1

Conditions: Locally Advanced or Metastatic NSCLC

Treatments: Drug: PBF-1129

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03274479

PBF-1129CT_03

Details and patient eligibility

About

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.

Enrollment: 18 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

• Written informed consent and any locally-required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluations

• Subject is willing and able to comply with the protocol for the duration of the study

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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18 participants in 4 patient groups

PBF-1129_40mg

Experimental group

Treatment:

Drug: PBF-1129

PBF-1129_80mg

Experimental group

Treatment:

Drug: PBF-1129

PBF-1129_160mg

Experimental group

Treatment:

Drug: PBF-1129

PBF-1129_320mg

Experimental group

Treatment:

Drug: PBF-1129