Non-small Cell Lung Cancer (NSCLC)Phase 1AdenONCONCT02403193
Trial of PBF-509 and PDR001 in Patients With Advanced Non-small Cell Lung Cancer (NSCLC)
A Phase 1 study testing PBF-509_80 mg, PBF-509_160 mg and PBF-509_320 mg in people with Non-small Cell Lung Cancer (NSCLC), run by Palobiofarma SL at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer (NSCLC)
- What is being tested?
- PBF-509_80 mg, PBF-509_160 mg and PBF-509_320 mg
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2015to 24 Nov 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/Ib Trial of Single Agent PBF-509 and in Combination With PDR001 for Patients With Advanced NSCLC
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.
Read the detailed description
A single institution phase I/Ib (dose escalation plus expansion) clinical trial of PBF-509 and combination treatment of PDR001 plus PBF-509 in Eastern Cooperative Oncology Group (ECOG) 0-1 patients with immunotherapy naïve and pretreated, advanced or metastatic NSCLC will be conducted to evaluate the safety, tolerability and preliminary efficacy of the combination.
The main objectives of the proposed Phase I trial will be:
Phase I Dose Escalation:
- To determine the safety and tolerability of PBF-509 during a phase I dose escalation trial
- Determine the pharmacokinetic profile of PBF-509
- Determine the safety profile of PBF-509
Phase 1 Dose Expansion:
- To further determine safety and tolerability of PBF-509 at the recommended phase II dose (RP2D)
Phase Ib Dose Escalation:
- To determine the dose limiting toxicities (DLT), maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of PBF-509 in combination with PDR001
- To determine the pharmacokinetics (PK) of PBF-509 in combination with PDR001
Phase Ib Expansion:
- To determine the safety and tolerability of PBF-509 in combination with PDR001, at the RP2D, in both immunotherapy naïve and pretreated advanced NSCLC
- To evaluate the response rate (ORR) of PBF-509 in combination with PDR001, at the RP2D, in both immunotherapy naïve and pretreated advanced NSCLC
- To evaluate the progression free (PFS) and overall survival (OS) of PBF-509 in combination with PDR001, at the RP2D, in both immunotherapy naïve and pretreated advanced NSCLC
- To determine the pharmacokinetics (PK) of PBF-509 in combination with PDR001
Correlative (Exploratory) Studies:
- To evaluate the biological activity of PBF-509 alone and in combination with PDR001 by assessment of potential pharmacodynamic (PD) biomarkers in tumor biopsy specimens of patients with advanced NSCLC
- To determine association of pre- or on-treatment expression of other immune checkpoints genes with resistance to single agent PBF-509 and dual immune inhibitory (PDR001+ PBF-509) treatment.
- Determine the pharmacokinetics of PDR001 in combination with PBF-509
The phase I and phase Ib dose escalations will be conducted utilizing the standard 3+3 dose escalation method. Pharmacokinetic (PK) data will be obtained for PBF-509 and PDR001.
The phase Ib dose expansion will consist of 2 independent groups of immunotherapy naïve and pretreated (previous immune checkpoint inhibitors; anti-CTLA-4, anti-PD-1, anti-PD-L1 and/or combinations) patients. Pharmacodynamic (PD) data will be obtained for potential biomarker analysis with pre-treatment and on-treatment tumor biopsies.
Number of Patients:
Phase I Dose escalation and safety expansion: 15-18 patients will be treated with single agent PBF-509 in escalation and up to 20 patients may be treated at the RP2D as a safety expansion group.
Phase Ib Dose escalation: 15-24 patients will be treated
The specific number of patients enrolled will vary depending on whether additional patients could be required during the escalation period if dose de-escalation cohorts or intermediate doses are enrolled, or when a dose-escalation cohort is expanded.
Phase Ib Dose Expansion: 20 patients per group will be enrolled for a total of 40 patients. Assuming 10-15% eligibility/screen failures, a maximum 50 patients will be enrolled.
Safety Assessments:
The maximun tolerated dose (MTD) evaluation will be based on the dose-limiting toxicity (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.
The safety evaluation will be based on the treated Population, which includes all patients who receive any dose of investigational product, and will include adverse events (AEs), serious adverse event (SAEs), laboratory evaluations and electrocardiogram (ECG) results.
AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 and described by system organ class and preferred tem using the Medical Dictionary for Regulatory Activities (MedDRA). Clinically relevant Laboratory abnormalities with toxicity grades according to the NCI CTCAE v4.03 will be derived and summarized.
Efficacy Assessments:
The efficacy analysis will be based on the treated Population which includes all patients who receive any dose of either investigational product. The following efficacy endpoints will be analyzed:
- Objective Response Rate (ORR) is defined as confirmed complete response (CR) or partial response (PR) based on modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Disease control rate (DCR) is defined as CR, PR, or stable disease (SD) based on modified RECIST v1.1.
- Duration of response (DoR) is defined as the duration from the first documentation of Objective response (OR) to the first documented disease progression or death due to any cause, whichever occurs first.
- Progression-free survival (PFS) will be measured from the start of treatment until the documentation of disease progression or death due to any cause, whichever occurs first.
- Overall survival (OS) will be determined as the time from the start of treatment with PDR001 and PBF-509 until death due to any cause
- Conditions
- Non-small Cell Lung Cancer (NSCLC)
- Being tested
- PBF-509_80 mg, PBF-509_160 mg, PBF-509_320 mg, PBF-509_640 mg, Combo PBF-509 (160 mg) + PDR001
- Keywords
- Adenosine A2a receptor antagonist, NSCLC, PBF-509, Immunotherapy, adenosine, PDR001, immune checkpoint inhibitors, Programmed Death-1 (PD-1) receptor, Adenosine A2a receptor (A2AR)
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PBF-509_80 mgDrug
PBF-509: 80 mg, PO, twice daily (BID)
PBF-509_160 mgDrug
PBF-509: 160 mg, PO, twice daily (BID)
PBF-509_320 mgDrug
PBF-509: 320 mg, PO, twice daily (BID)
PBF-509_640 mgDrug
PBF-509: 640 mg, PO, twice daily (BID)
Combo PBF-509 (160 mg) + PDR001Drug
Drug 1: PDR001 administered intravenously. Drug 2: PBF-509 administered orally
Combo PBF-509 (320 mg) + PDR001Drug
Drug 1: PDR001 administered intravenously. Drug 2: PBF-509 administered orally
Combo PBF-509 (640 mg) + PDR001Drug
Drug 1: PDR001 administered intravenously. Drug 2: PBF-509 administered orally
RP2D (PBF-509+PDR001)_immuno naïveDrug
Drug 1: PDR001 administered intravenously. Drug 2: PBF509 administered orally
Experimental: RP2D (PBF-509+PDR001)_immuno treatedDrug
Drug 1: PDR001 administered intravenously. Drug 2: PBF509 administered orally
| Study group | Role | What they receive |
|---|---|---|
| PBF-509_80 mg | Experimental | Not described Receives: Drug: PBF-509_80 mg |
| PBF-509_160 mg | Experimental | Not described Receives: Drug: PBF-509_160 mg |
| PBF-509_320 mg | Experimental | Not described Receives: Drug: PBF-509_320 mg |
| PBF-509_640 mg | Experimental | Not described Receives: Drug: PBF-509_640 mg |
| PBF509_160 mg +PDR001 | Experimental | Not described Receives: Drug: Combo PBF-509 (160 mg) + PDR001 |
| PBF509_320 mg+PDR001 | Experimental | Not described Receives: Drug: Combo PBF-509 (320 mg) + PDR001 |
| PBF509_640 mg +PDR001 | Experimental | Not described Receives: 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. Receives: 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. Receives: Drug: Experimental: RP2D (PBF-509+PDR001)_immuno treated |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 56 days
Secondary outcomes (16)
Time to PBF-509 peak concentration in plasma "Tmax"
The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration.
It will consist in the time (in minutes) to reach the maximum "PBF-509" concentration in plasma samples of patients after oral administration of PBF-509.
Measured: 8 days
Time to PBF-509 peak concentration in plasma at steady state "Tmax,ss"
The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration.
It will consist in the time (in minutes) to reach the maximum "PBF-509" concentration in plasma samples of patients during a dosing interval at steady state.
Measured: 8 days
PBF-509 peak concentration in plasma "Cmax"
The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration.
It will consist in the maximum plasma concentration (ng/mL) of PBF-509 observed after administration.
Measured: 8 days
PBF-509 peak concentration in plasma at steady state"Cmax,ss"
The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration.
It will consist in the maximum plasma concentration (ng/mL) of PBF-509 observed during a dosing interval at steady state.
Measured: 8 days
The area under PBF-509 plasma concentration-time curve to infinite time "AUC(0-inf)"
The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration.
It will consist in the area under the concentration-time curve from zero up to ∞ with extrapolation of the terminal phase. "AUC(0-inf)" will be given in Amount·time/ volume units
Measured: 8 days
The area under PBF-509 plasma concentration-time curve up to time 't' "AUC(0-t)"
The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration.
It will consist in the area under the concentration-time curve from zero up to a definite time t. "AUC(0-t)" will be given in Amount·time/ volume units.
Measured: 8 days
The area under PBF-509 plasma concentration-time curve over the dosing interval "AUC(0-τ)"
The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration.
It will consist in the area under the concentration-time curve over the dosing interval. "AUC(0-τ)" will be given in Amount·time/ volume units.
Measured: 8 days
PBF-509 half-life in plasma " t½"
The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration.
It will consist in the terminal half-life of PBF-509 in plasma. "t½" will be given in hours (h)
Measured: 8 days
PBF-509 apparent volume of distribution following extravascular administration"Vd/F"
The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration.
It will consist in the apparent volume of distribution during terminal phase after oral / extravascular administration. "Vd/F" will be given in Volume or volume/kg units.
Measured: 8 days
PBF-509 total body clearance following extravascular administration "Cl/F"
The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration.
It will consist in the apparent total plasma or serum clearance of drug after oral administration. "Cl/F" will be given in the Volume/ time or volume/ time/ kg units.
Measured: 8 days
The PBF 509 accumulation index "Rac"
The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration.
It will consist in the accumulation ratio calculated from Cmax,ss at steady state and Cmax after single dosing.
Measured: 8 days
Efficacy as measured by Objective response rate (ORR)
ORR: Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).
ORR is defined as confirmed complete response (CR) or partial response (PR) based on modified RECIST v1.1.
Measured: 3 years
Efficacy as measured by Disease control rate (DCR)
The disease control rate (DCR) will be estimated considering the following variables:
Complete response (CR), Partial response (PR) and stable disease (SD) as described by Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).
These variables will be assessed based on Imaging-based evaluation methods as chest x-ray, conventional computed tomography (CT) and magnetic resonance imaging (MRI) that will be performed every 2 cycles of 28 days administration
Measured: 3 years
Efficacy as measured by duration of response (DoR)
Duration of response (DoR) is defined as the duration from the first documentation of OR to the first documented disease progression or death due to any cause, whichever occurs first.
Measured: 3 years
Efficacy as measured by progression-free survival (PFS)
Progression-free survival (PFS) will be measured from the start of treatment until the documentation of disease progression or death due to any cause, whichever occurs first. For subjects who are alive and progression-free at the time of data cut-off for analysis, PFS will be censored at the last tumor assessment date.
Measured: 3 years
Efficacy as measured by overall survival (OS)
Overall survival (OS) will be determined as the time from the start of treatment until death due to any cause.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2015 (estimated)
- Study startOct 2015
- Primary completionOct 2021
- Study completion24 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-small Cell Lung Cancer (NSCLC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- Palobiofarma SL
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Novartis, H. Lee Moffitt Cancer Center and Research Institute
- Responsible party
- Sponsor
- Investigators
- Alberto Chiappori, MD, Principal investigator, Moffitt Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02403193
- Sponsor's protocol ID
- MC18321
- Acronym
- AdenONCO
- Status last verified
- Jan 2022
- First submitted
- 17 Mar 2015
- Last updated
- 12 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 35254415
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/Ib Trial of Single Agent PBF-509 and in Combination With PDR001 for Patients With Advanced NSCLC
- ClinicalTrials.gov ID
- NCT02403193
- Acronym / sponsor ID
- AdenONCO / MC18321
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- Palobiofarma SLIndustry (pharma, biotech, devices)
- Collaborators
- Novartis, H. Lee Moffitt Cancer Center and Research Institute
- Study start
- Oct 2015
- Primary completion
- Oct 2021 (actual)
- Study completion
- 24 Nov 2021 (actual)
- First posted
- 31 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
A single institution phase I/Ib (dose escalation plus expansion) clinical trial of PBF-509 and combination treatment of PDR001 plus PBF-509 in Eastern Cooperative Oncology Group (ECOG) 0-1 patients with immunotherapy naïve and pretreated, advanced or metastatic NSCLC will be conducted to evaluate the safety, tolerability and preliminary efficacy of the combination.
The main objectives of the proposed Phase I trial will be:
Phase I Dose Escalation:
- To determine the safety and tolerability of PBF-509 during a phase I dose escalation trial
- Determine the pharmacokinetic profile of PBF-509
- Determine the safety profile of PBF-509
Phase 1 Dose Expansion:
- To further determine safety and tolerability of PBF-509 at the recommended phase II dose (RP2D)
Phase Ib Dose Escalation:
- To determine the dose limiting toxicities (DLT), maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of PBF-509 in combination with PDR001
- To determine the pharmacokinetics (PK) of PBF-509 in combination with PDR001
Phase Ib Expansion:
- To determine the safety and tolerability of PBF-509 in combination with PDR001, at the RP2D, in both immunotherapy naïve and pretreated advanced NSCLC
- To evaluate the response rate (ORR) of PBF-509 in combination with PDR001, at the RP2D, in both immunotherapy naïve and pretreated advanced NSCLC
- To evaluate the progression free (PFS) and overall survival (OS) of PBF-509 in combination with PDR001, at the RP2D, in both immunotherapy naïve and pretreated advanced NSCLC
- To determine the pharmacokinetics (PK) of PBF-509 in combination with PDR001
Correlative (Exploratory) Studies:
- To evaluate the biological activity of PBF-509 alone and in combination with PDR001 by assessment of potential pharmacodynamic (PD) biomarkers in tumor biopsy specimens of patients with advanced NSCLC
- To determine association of pre- or on-treatment expression of other immune checkpoints genes with resistance to single agent PBF-509 and dual immune inhibitory (PDR001+ PBF-509) treatment.
- Determine the pharmacokinetics of PDR001 in combination with PBF-509
The phase I and phase Ib dose escalations will be conducted utilizing the standard 3+3 dose escalation method. Pharmacokinetic (PK) data will be obtained for PBF-509 and PDR001.
The phase Ib dose expansion will consist of 2 independent groups of immunotherapy naïve and pretreated (previous immune checkpoint inhibitors; anti-CTLA-4, anti-PD-1, anti-PD-L1 and/or combinations) patients. Pharmacodynamic (PD) data will be obtained for potential biomarker analysis with pre-treatment and on-treatment tumor biopsies.
Number of Patients:
Phase I Dose escalation and safety expansion: 15-18 patients will be treated with single agent PBF-509 in escalation and up to 20 patients may be treated at the RP2D as a safety expansion group.
Phase Ib Dose escalation: 15-24 patients will be treated
The specific number of patients enrolled will vary depending on whether additional patients could be required during the escalation period if dose de-escalation cohorts or intermediate doses are enrolled, or when a dose-escalation cohort is expanded.
Phase Ib Dose Expansion: 20 patients per group will be enrolled for a total of 40 patients. Assuming 10-15% eligibility/screen failures, a maximum 50 patients will be enrolled.
Safety Assessments:
The maximun tolerated dose (MTD) evaluation will be based on the dose-limiting toxicity (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.
The safety evaluation will be based on the treated Population, which includes all patients who receive any dose of investigational product, and will include adverse events (AEs), serious adverse event (SAEs), laboratory evaluations and electrocardiogram (ECG) results.
AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 and described by system organ class and preferred tem using the Medical Dictionary for Regulatory Activities (MedDRA). Clinically relevant Laboratory abnormalities with toxicity grades according to the NCI CTCAE v4.03 will be derived and summarized.
Efficacy Assessments:
The efficacy analysis will be based on the treated Population which includes all patients who receive any dose of either investigational product. The following efficacy endpoints will be analyzed:
- Objective Response Rate (ORR) is defined as confirmed complete response (CR) or partial response (PR) based on modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Disease control rate (DCR) is defined as CR, PR, or stable disease (SD) based on modified RECIST v1.1.
- Duration of response (DoR) is defined as the duration from the first documentation of Objective response (OR) to the first documented disease progression or death due to any cause, whichever occurs first.
- Progression-free survival (PFS) will be measured from the start of treatment until the documentation of disease progression or death due to any cause, whichever occurs first.
- Overall survival (OS) will be determined as the time from the start of treatment with PDR001 and PBF-509 until death due to any cause
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| 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 | Drug: RP2D (PBF-509+PDR001)_immuno naïveImmunotherapy naïve patients will be treated at the combination RP2D previously determined in the phase Ib, dose escalation portion of the trial. |
| RP2D (PBF-509+PDR001)_immuno treated | Experimental | Drug: Experimental: RP2D (PBF-509+PDR001)_immuno treatedPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PBF-509_80 mgPBF-509: 80 mg, PO, twice daily (BID) | Drug | PBF-509_80 mg |
| PBF-509_160 mgPBF-509: 160 mg, PO, twice daily (BID) | Drug | PBF-509_160 mg |
| PBF-509_320 mgPBF-509: 320 mg, PO, twice daily (BID) | Drug | PBF-509_320 mg |
| PBF-509_640 mgPBF-509: 640 mg, PO, twice daily (BID) | Drug | PBF-509_640 mg |
| Combo PBF-509 (160 mg) + PDR001Drug 1: PDR001 administered intravenously. Drug 2: PBF-509 administered orally | Drug | PBF509_160 mg +PDR001 |
| Combo PBF-509 (320 mg) + PDR001Drug 1: PDR001 administered intravenously. Drug 2: PBF-509 administered orally | Drug | PBF509_320 mg+PDR001 |
| Combo PBF-509 (640 mg) + PDR001Drug 1: PDR001 administered intravenously. Drug 2: PBF-509 administered orally | Drug | PBF509_640 mg +PDR001 |
| RP2D (PBF-509+PDR001)_immuno naïveDrug 1: PDR001 administered intravenously. Drug 2: PBF509 administered orally | Drug | RP2D (PBF-509+PDR001)_immuno naïve |
| Experimental: RP2D (PBF-509+PDR001)_immuno treatedDrug 1: PDR001 administered intravenously. Drug 2: PBF509 administered orally | Drug | RP2D (PBF-509+PDR001)_immuno treated |
Primary outcome
Maximum Tolerated Dose (MTD) of PBF-509 as single agent
Time frame: 28 days
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.
Maximum Tolerated Dose (MTD) of the combination (PBF-509+PDR001) treatment
Time frame: 56 days
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.
16 secondary outcomes
Time to PBF-509 peak concentration in plasma "Tmax"
Time frame: 8 days
Time to PBF-509 peak concentration in plasma at steady state "Tmax,ss"
Time frame: 8 days
PBF-509 peak concentration in plasma "Cmax"
Time frame: 8 days
PBF-509 peak concentration in plasma at steady state"Cmax,ss"
Time frame: 8 days
The area under PBF-509 plasma concentration-time curve to infinite time "AUC(0-inf)"
Time frame: 8 days
The area under PBF-509 plasma concentration-time curve up to time 't' "AUC(0-t)"
Time frame: 8 days
The area under PBF-509 plasma concentration-time curve over the dosing interval "AUC(0-τ)"
Time frame: 8 days
PBF-509 half-life in plasma " t½"
Time frame: 8 days
PBF-509 apparent volume of distribution following extravascular administration"Vd/F"
Time frame: 8 days
PBF-509 total body clearance following extravascular administration "Cl/F"
Time frame: 8 days
The PBF 509 accumulation index "Rac"
Time frame: 8 days
Efficacy as measured by Objective response rate (ORR)
Time frame: 3 years
Efficacy as measured by Disease control rate (DCR)
Time frame: 3 years
Efficacy as measured by duration of response (DoR)
Time frame: 3 years
Efficacy as measured by progression-free survival (PFS)
Time frame: 3 years
Efficacy as measured by overall survival (OS)
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2022.
- Derived from this study: PubMed 35254415Chiappori 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.
- 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"Link provided by the sponsor.
- 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"Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alberto Chiappori, MD principal investigator
Moffitt Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PBF-509_80 mg, PBF-509_160 mg and PBF-509_320 mg in people with Non-small Cell Lung Cancer (NSCLC), run by Palobiofarma SL at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) of PBF-509 as single agent (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02403193, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2022.