Trial of PBF-509 and PDR001 in Patients With Advanced Non-small Cell Lung Cancer (NSCLC)

NCT02403193 | Completed Phase 1

• 1 other identifier: MC18321
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety, tolerability, feasibility and preliminary efficacy of the administration of PBF-509 (Adenosine A2a receptor antagonist) as single agent or in combination with PDR001 (programmed cell death 1 receptor antibody (PD-1 Ab)) to NSCLC patients.

Conditions

Non-small Cell Lung Cancer (NSCLC)

Keywords

Adenosine A2a receptor antagonist; NSCLC; PBF-509; Immunotherapy; adenosine; PDR001; immune checkpoint inhibitors; Programmed Death-1 (PD-1) receptor; Adenosine A2a receptor (A2AR)

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of PBF-509 as single agent

  The MTD evaluation will be based on the DLT Evaluable Population which includes all patients enrolled in the dose-escalation portion of the trial, who receive the protocol-assigned treatment with PBF-509 and complete the safety follow-up through the DLT evaluation period, or experience a DLT during the DLT evaluation period.

  28 days

• Maximum Tolerated Dose (MTD) of the combination (PBF-509+PDR001) treatment

  The MTD evaluation will be based on the DLT Evaluable Population which includes all patients enrolled in the dose-escalation portion of the trial, who receive the protocol-assigned treatment with PDR001 and PBF-509 and complete the safety follow-up through the DLT evaluation period, or experience a DLT during the DLT evaluation period.

  56 days

Secondary Outcomes (16)

• Time to PBF-509 peak concentration in plasma "Tmax"

  8 days

• Time to PBF-509 peak concentration in plasma at steady state "Tmax,ss"

  8 days

• PBF-509 peak concentration in plasma "Cmax"

  8 days

• PBF-509 peak concentration in plasma at steady state"Cmax,ss"

  8 days

• The area under PBF-509 plasma concentration-time curve to infinite time "AUC(0-inf)"

  8 days

Study Arms (9)

PBF-509_80 mg

EXPERIMENTAL

Drug: PBF-509_80 mg

PBF-509_160 mg

EXPERIMENTAL

Drug: PBF-509_160 mg

PBF-509_320 mg

EXPERIMENTAL

Drug: PBF-509_320 mg

PBF-509_640 mg

EXPERIMENTAL

Drug: PBF-509_640 mg

PBF509_160 mg +PDR001

EXPERIMENTAL

Drug: Combo PBF-509 (160 mg) + PDR001

PBF509_320 mg+PDR001

EXPERIMENTAL

Drug: Combo PBF-509 (320 mg) + PDR001

PBF509_640 mg +PDR001

EXPERIMENTAL

Drug: Combo PBF-509 (640 mg) + PDR001

RP2D (PBF-509+PDR001)_immuno naïve

EXPERIMENTAL

Immunotherapy naïve patients will be treated at the combination RP2D previously determined in the phase Ib, dose escalation portion of the trial.

Drug: RP2D (PBF-509+PDR001)_immuno naïve

RP2D (PBF-509+PDR001)_immuno treated

EXPERIMENTAL

Patients previously treated with immunotherapy (previous immune checkpoint inhibitors; anti-CTLA-4, anti-PD-1, anti-PD-L1 and/or combinations) will be treated at the combination RP2D previously determined in the phase Ib, dose escalation portion of the trial.

Drug: Experimental: RP2D (PBF-509+PDR001)_immuno treated

Interventions

PBF-509_80 mg DRUG

PBF-509: 80 mg, PO, twice daily (BID)

PBF-509_80 mg

PBF-509_160 mg DRUG

PBF-509: 160 mg, PO, twice daily (BID)

PBF-509_160 mg

PBF-509_320 mg DRUG

PBF-509: 320 mg, PO, twice daily (BID)

PBF-509_320 mg

PBF-509_640 mg DRUG

PBF-509: 640 mg, PO, twice daily (BID)

PBF-509_640 mg

Combo PBF-509 (160 mg) + PDR001 DRUG

Drug 1: PDR001 administered intravenously. Drug 2: PBF-509 administered orally

PBF509_160 mg +PDR001

Combo PBF-509 (320 mg) + PDR001 DRUG

Drug 1: PDR001 administered intravenously. Drug 2: PBF-509 administered orally

PBF509_320 mg+PDR001

Combo PBF-509 (640 mg) + PDR001 DRUG

Drug 1: PDR001 administered intravenously. Drug 2: PBF-509 administered orally

PBF509_640 mg +PDR001

RP2D (PBF-509+PDR001)_immuno naïve DRUG

Drug 1: PDR001 administered intravenously. Drug 2: PBF509 administered orally

RP2D (PBF-509+PDR001)_immuno naïve

Experimental: RP2D (PBF-509+PDR001)_immuno treated DRUG

Drug 1: PDR001 administered intravenously. Drug 2: PBF509 administered orally

RP2D (PBF-509+PDR001)_immuno treated

Eligibility Criteria

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

You may qualify if:

• Patients must have histologic or cytologic diagnosis of advanced/metastatic NSCLC. For those with mixed histology, there must be a predominant histology.
• Patients must previously have received at least one prior line of therapy for their disease
• EGFR mutation with exon 19 deletion or L858R mutation (Exon 21) or ALK rearrangement positive must have failed prior TKI therapy
• Able, willing to give written consent for available archival tumor samples (not mandatory) and tumor biopsies before and during protocol therapy (mandatory).
• Prior immunotherapy is allowed (previous immune checkpoint inhibitors; anti-CTLA-4, anti-PD-1, anti-PD-L1 and/or combinations), except for the patients enrolled to the immunotherapy naïve group of the phase IB dose expansion.
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>20 mm with conventional techniques or as \>10 mm with spiral computed tomography (CT) scan, Magnetic resonance imaging (MRI), or calipers by clinical exam. See Section 13.
• Written informed consent and any locally-required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
• Age \> 18 years at time of study entry
• Eastern Cooperative Oncology Group (ECOG) 0-1
• Adequate normal organ and marrow function
• Female patients must either be of non-reproductive potential (ie, post-menopausal by history: ≥60 years old or no menses for 1 year without an alternative medical cause; OR history of complete hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use 2 highly effective methods of contraception while taking study treatment and for 90 days after the last dose of study treatment.
• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

You may not qualify if:

• Symptomatic and/or untreated Brain Metastases
• Pregnancy or breast feeding
• Serious uncontrolled medical disorder or active infection that in the investigator's opinion would impair the patient's ability to receive study treatment.
• Concurrent use of other anticancer approved or investigational agents is not allowed.
• 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.
• Prior malignancy in past 2 years or as identified in Section 7.2 of this protocol
• 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)
• Concurrent administration of strong inhibitors or moderate inducers of CYP1A2 is not permitted; administration must be discontinued at least 7 days prior to initiating study drug administration.

Sponsors & Collaborators

• Palobiofarma SL: lead
• Novartis: collaborator
• H. Lee Moffitt Cancer Center and Research Institute: collaborator

Study Sites (1)

H.Lee Moffitt Cancer center

Tampa, Florida, 33612, United States

Location

Related Publications (1)

• Chiappori AA, Creelan B, Tanvetyanon T, Gray JE, Haura EB, Thapa R, Barlow ML, Chen Z, Chen DT, Beg AA, Boyle TA, Castro J, Morgan L, Morris E, Aregay M, Hurtado FK, Manenti L, Antonia S. Phase I Study of Taminadenant (PBF509/NIR178), an Adenosine 2A Receptor Antagonist, with or without Spartalizumab (PDR001), in Patients with Advanced Non-Small Cell Lung Cancer. Clin Cancer Res. 2022 Jun 1;28(11):2313-2320. doi: 10.1158/1078-0432.CCR-21-2742.

  PMID: 35254415 DERIVED

Related Links

• Randomized, Double Blind, Placebo Controlled "first in-human" Study to Assess the Safety and Tolerability of Single Ascending Oral Doses of PBF-509 in Male Healthy Volunteers"
• Randomized, double blind, placebo controlled, parallel groups study to assess the safety, tolerability and pharmacokinetic profile of PBF-509 (80 mg, 160 mg and 240 mg) after multiple oral doses" in healthy volunteers"

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

spartalizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Alberto Chiappori, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 17, 2015
• First Posted: March 31, 2015
• Study Start: October 1, 2015
• Primary Completion: October 1, 2021
• Study Completion: November 24, 2021
• Last Updated: January 12, 2022

Record last verified: 2022-01

Locations

US (1)