Clinical trial NCT03786484: Study of PBF-999 in Solid Tumour Advanced Cancer
Official title: Phase I/Ib Trial of Single Agent PBF-999 in Solid Tumour Advanced Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: solid tumors
PDE10 inhibitors
Immunoncology
Lead sponsor: Palobiofarma SL
Sponsor class: INDUSTRY
Collaborators: name: Vall d'Hebron institute of oncology (VHIO), Catalan institute of oncology (Hospitalet) (ICO)
First posted: 2018-12-26
Enrollment: 54
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Multicentric phase I (dose escalation plus expansion) clinical trial of PBF-999 in patients with immunotherapy naïve and pretreated solid tumors to evaluate the safety, tolerability and preliminary efficacy of the compound

Detailed description: The phase I dose escalations will be conducted utilizing the standard 3+3 dose escalation method. Pharmacokinetic (PK) data will be obtained for PBF-999.

The phase I dose expansion will consist of 1 group including immunotherapy naïve and pretreated (previous immune checkpoint inhibitors; anti-CTLA-4, anti-PD-1, anti-PD-L1 and/or combinations) solid tumors cancer patients. Pharmacodynamic (PD) data will be obtained for potential biomarker analysis with pre-treatment and on-treatment tumor biopsies.

Phase I Dose Escalation (3+3 Design):

1. The MTD will be defined as the highest dose level at which less than 2 out of 6 patients (\<33%) experience DLT in Cycle 1 (first 28 days).

Phase I Safety Expansion Once RP2D has been declared for PBF-999 using the standard 3+3 design, up to 20 additional solid tumor cancer patients may be treated at the RP2D to further explore safety and tolerability of the selected PBF-999 dose.

Patients in this study will be males or females 18 years of age or older. Patients must have histologically or cytologically confirmed cancer with at least one measurable lesion, with adequate organ and marrow function, and with ECOG performance status of 0-1. Eligible patients must have received at least one prior line of therapy for their disease.

Eligibility criteria: Inclusion Criteria:

* Advanced/metastatic histologically confirmed solid tumor
* At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
* Patients who has progressed to the standard therapy
* ECOG performance status of 0/1
* Age greater than 18 years.
* Adequate bone marrow, renal and hepatic function
* Able and willing to give valid written consent for available archival tumor samples (not mandatory) and tumor biopsies before and during protocol (immune)therapy (not mandatory but highly recommended).
* Prior immunotherapy is allowed

Exclusion Criteria:

* Participation in another clinical study with an investigational product during the last 4 weeks or 5 half-lifes prior to starting on treatment.
* 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
* 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.

Primary outcomes:
measure: Number of Adverse Events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03
timeFrame: 28 Days
measure: The Maximun Tolerated Dose (MTD) of PBF-999
timeFrame: 28 Days
Secondary outcomes:
measure: Time to PBF-999 peak concentration in plasma "Tmax
timeFrame: Day 1, Day 8 and Day 29
measure: PBF-999 peak concentration in plasma "Cmax"
timeFrame: Day 1, Day 8 and Day 29
measure: The area under PBF-999 plasma concentration-time curve to infinite time "AUC(0-inf)
timeFrame: Day 1, Day 8 and Day 29
measure: PBF-999 half-life in plasma " t½"
timeFrame: Day 1, Day 8 and Day 29
measure: Efficacy of PBF-999 treatment as measured by Objective response rate (ORR
timeFrame: 2 years
measure: Efficacy of PBF-999 as measured by Disease control rate (DCR)
timeFrame: 2 years
measure: Efficacy of PBF-999 as measured by duration of response (DoR)
timeFrame: 2 years
measure: Efficacy of PBF-999 as measured by progression-free survival (PFS)
timeFrame: 2 years
measure: Efficacy of PBF-999 as measured by overall survival (OS)
timeFrame: 2 years
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Vall d'Hebron institute of oncology (VHIO)
Study officials:
References: