PBF-1129 and Nivolumab for the Treatment of Recurrent or Metastatic Non-Small Cell Lung Cancer

NCT05234307 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: OSU-21156NCI-2022-00236R01CA248741
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of PBF-1129 in combination with nivolumab in treating patients with non-small cell lung cancer that has come back (recurrent) or spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as PBF-1129 and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Conditions

Metastatic Lung Non-Small Cell Carcinoma; Recurrent Lung Non-Small Cell Carcinoma; Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events

  Safety will be measured by the occurrence of dose-limited toxicities as well as any other adverse events as defined in Common Terminology Criteria for Adverse Events version 5. Frequency and severity of adverse events and tolerability of the regimen will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. All patients who have received at least one dose of the therapeutic agents will be evaluable for toxicity and tolerability.

  Up to 30 days after the last dose of study treatment

Secondary Outcomes (4)

• Overall objective response rate

  Up to 1 year after treatment discontinuation

• Disease control rate

  Up to 1 year after treatment discontinuation

• Overall survival

  Up to 1 year after treatment discontinuation

• Progression free survival

  Up to 1 year after treatment discontinuation

Other Outcomes (2)

• Levels of myeloidderived suppressor cells (MDSC)

  Up to 1 year after treatment discontinuation

• Correlative biomarkers

  Up to 1 year after treatment discontinuation

Study Arms (1)

Treatment (PBF-1129, nivolumab)

EXPERIMENTAL

Patients receive PBF-1129 PO QD and nivolumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Adenosine A2B Receptor Antagonist PBF-1129; Procedure: Biospecimen Collection; Biological: Nivolumab

Interventions

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo

Treatment (PBF-1129, nivolumab)

Adenosine A2B Receptor Antagonist PBF-1129 DRUG

Given PO

Also known as: A2BR Antagonist PBF-1129, PBF 1129, PBF-1129, PBF1129

Treatment (PBF-1129, nivolumab)

Biospecimen Collection PROCEDURE

Correlative studies

Also known as: Biological Sample Collection, Biospecimen Collected

Treatment (PBF-1129, nivolumab)

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years
• Confirmed recurrent or metastatic non-small cell carcinoma of the lung of any histology without curative options
• Measurable disease based on RECIST 1.1
• Patients must have received standard of care chemotherapy and immunotherapy. No limits to prior lines of therapy. Prior PD-1 and/or PD-L1 directed therapies are required. Prior CTLA4 therapy is permitted. Patients may have received no more than 3 prior lines of therapy in the metastatic setting (excluding targeted therapies)
• Patients with known actionable mutations with Food and Drug Administration (FDA)-approved treatment options must have received all approved and standard of care treatment options (ie osimertinib for EGFR, alectinib for ALK, etc)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Absolute neutrophil count (ANC) \>= 1,500 /mcL
• Platelets \>= 100,000 / mcL
• Serum creatinine OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) =\< 1.5 X upper limit of normal (ULN) OR \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN
• Serum total bilirubin =\< 1.5 X ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN
• AAspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 X ULN OR =\< 5 X ULN for subjects with liver metastases
• Albumin \>= 2.5 mg/dL
• International normalized ratio (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Anticipated life expectancy of \>= 3 months
• Willing to comply with study procedures

You may not qualify if:

• Has active autoimmune disease, including myasthenic syndrome, which has required systemic treatment in the past 12 months (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided that disease is well controlled at baseline and requires only topical corticosteroids.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (at a dose \> 10 mg prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Known active chronic infections - human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), known active (ie with detectable polymerase chain reaction \[PCR\]) Hepatitis B or C
• Cirrhosis (Child-Pugh B or worse) or cirrhosis with history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis
• Symptomatic central nervous system (CNS) metastases. Patients with treated brain metastases are eligible if they are clinically stable with regard to neurologic function, on stable dose of steroids after cranial irradiation with maximum of 10 mg prednisone equivalent. Treatment (whole brain radiation therapy, focal radiation therapy, and stereotactic radiosurgery) must be completed at least 2 weeks prior to study entry, or after surgical resection performed at least 28 days prior to treatment initiation. Patients with asymptomatic lesions will be eligible if considered appropriate by the treating physician.
• Pregnancy or breastfeeding
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (corrected QT \[QTc\] using Fredericia's formula \[QTcF\]) \> 470 msec (Fridericia's Criteria for Corrected QT interval \[QTc\] Calculation: Fridericia's formula QTcF = (QT/RR0.33). RR is the time from the interval of 1 QRS complex to the next measured in seconds and is commonly calculated as (60/heart rate \[HR\])
• Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) (e.g., complete left bundle branch block, third degree heart block, second degree heart block
• Any patient who experience unacceptable toxicity on prior checkpoint inhibitor therapy:
• \>= grade 3 adverse event (AE) related to checkpoint inhibitor with the exception of grade 3 pneumonitis that has resolved to grade 1 at time of study entry.
• Ongoing \>= grade 2 immune-related AE associated with checkpoint inhibitor with the exception of endocrine toxicities as detailed below
• CNS, ocular or cardiac AE of any grade related to checkpoint inhibitor
• NOTE: Patients with a prior endocrine AE are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• Dwight Owen: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Dwight H Owen, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 1, 2022
• First Posted: February 10, 2022
• Study Start: November 21, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 6, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)