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ITR-251 in Patients With Advanced Solid Tumors

ConditionsSolid Tumor CancerCastration Resistant Metastatic Prostate Cancer
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorITERIA BIOPHARMA, S.L.

About this trial

This is an open-label, Phase I/Ib trial including an initial dose-escalation phase in patients with advanced solid tumors and a dose-expansion phase at recommended phase 2 dose (RP2D) in combination with Androgen Receptor Pathway Inhibitors (ARPi) in patients with metastatic castration resistant prostate cancer (mCRPC).

The trial will enroll following a 3+3 design up to 6 patients with any type of solid tumors after progression to standard treatments at each dose level during the dose-escalation phase. Four dose levels are planned. If the first DL is deemed not safe, the next patients could be treated at a lower dose. If further reductions are required, the study will be stopped. After determining the RP2D, the trial will enroll up to 20 additional evaluable patients with mCRPC during the dose-expansion phase. The first six patients enrolled in the dose-expansion phase will be the safety lead in cohort for the combination and will be monitored for DLTs. The rest of patients will be enrolled afterwards at the RP2D if found safe or with a lower ITR-251 dose level if the combination shows unacceptable toxicity.

The study aims to determine the RP2D of ITR-251 and the safety in combination with ARPi in mCRPC. Secondary objectives includes duration of treatment, tolerability, pharmacokinetics, and preliminary signs of antitumoral activity and efficacy. Pharmacodynamics will be an exploratory objective.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients must be fully informed about the study and sign the informed consent form (ICF) before any study specific assessment.

Patients ≥18 years old at the time of signing the informed consent.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 prior to study entry.

Have measurable disease per RECIST v1.1 or PCWG4 criteria (for mCRPC).

Disqualifiers

For Dose-escalation phase only: women pregnant or breastfeeding.

For Dose-escalation phase only: Patients with glioblastoma, cholangiocarcinoma, gastric, liver, or nasopharyngeal carcinomas.

For dose-expansion phase only: patients with symptomatic or radiologic PD requiring or tributary for treatment with docetaxel or other concurrent anticancer therapies other than ADT and ARPi.

Patients with brain metastasis.

Trial design

Design model

Sequential

Treatments tested in this trial

  • ITR-251

    Drug

    ITR-251 is a potent and selective inhibitor of Monoamine Oxidase A (MAO-A) with reversible inhibition and limited capacity for blood brain barrier (BBB) crossing. Four dose levels will be tested. Dose could be also reduced to dose level -1.

  • ITR-251 at RP2D

    Drug

    ITR-251 is a potent and selective inhibitor of MAO-A with reversible inhibition and limited capacity for blood brain barrier (BBB) crossing. Dose at RP2D

  • ARPI therapy

    Drug

    ARPIs are blockers of the androgen receptor pathway, which play a pivotal role in treating prostate cancer, showing significant efficacy across different disease stages. ARPi will be given according to standard clinical practice

  • Androgen Deprivation Therapy (ADT)

    Drug

    ADTs reduce availability of male hormones (androgens like testosterone) that fuel cancer growth and it is the backbone for many standard treatment combinations in prostate cancer, including in the castration resistant setting in combination with ARPis. ADT will be given according to standard clinical practice.

Treatment groups

46 Participants
are divided into 2 treatment groups
Group A: Dose-EscalationExperimental treatment 1 intervention
Group B: Dose-ExpansionExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

RP2D of ITR-251

During dose-escalation phase, patients will be included sequentially into cohorts with escalating dose levels. RP2D is defined as the highest dose level at which \<33% of patients reported a dose limiting toxicities (DLT) (i.e. ≤ 1 DLT out of 6 patients) providing the safety profile is amenable. DLT is defined as any of the following events during the DLT reporting period: 1. Hematologic toxicities: 1. Grade (G) 3 febrile neutropenia lasting \> 7 days 2. G4 thrombocytopenia lasting \> 7 days 3. G3 thrombocytopenia with clinically significant bleeding 4. Gr ≥3 anemia requiring urgent transfusion support 2. Non-hematologic toxicities: 1. Any G ≥3 non-hematologic toxicity, excluding non relevant nausea, vomiting, or diarrhea, laboratory abnormalities or cutaneous events. 2. Hypertensive crisis 3. Severe serotonin syndrome 4. G ≥3 arrhythmia 5. QTcF prolongation \>500 ms or increase \>60 ms from baseline 3. Received \< 75% of the intended ITR-251 dose during the DLT period due to toxicity

Time frame
DLT period is 28 days since first dose of study treatment
2

Treatment-emergent adverse events

incidence of treatment-emergent adverse events (TEAEs) classified by grade and seriousness

Time frame
Throughout the study period, approximately 12 months

Secondary outcomes

1

Duration of treatment

Defined as the time from the first dose of ITR-251 to the permanent discontinuation of ITR-251 treatment for any reason. Patients with treatment ongoing will have their last administration date as the last date on treatment for timing calculation.

Time frame
Throughout the study period, approximately 12 months
2

Incidence of treatment modifications

number of patients requiring treatment dose reduction, interruptions and permanent discontinuations for management of TEAEs

Time frame
Throughout the study period, approximately 12 months
3

Pharmacokinetic (PK) profile

Cmax and Tmax of ITR-251 will be reported. The study will include analysis of patients in fasted and fed conditions

Time frame
Within the first months of treatment with ITR-251
4

Objective response rate (ORR)

Proportion of patient who achieved a complete response (CR) or partial response (PR) according to prostate cancer working group (PCWG4) (in case of prostate cancer) or RECIST V1.1 (all other tumors). ORR will be assessed by investigators using computed tomography (CT) or magnetic resonance imaging (MRI) scans.

Time frame
Throughout the study period, approximately 12 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

ITERIA BIOPHARMA, S.L.

Lead sponsor

MFAR

Collaborator

Source ClinicalTrials.gov

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