Solid TumorPhase 1NCT04675996
First-in-Human Study of INT-1B3 in Patients With Advanced Solid Tumors
A Phase 1 study testing INT-1B3 in people with Solid Tumor, run by InteRNA at 4 sites in 2 countries.
Trial summary
This is a 2 part, multi-center, open-label, First-in-Human clinical study to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of INT-1B3 in the treatment of patients with advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor
- What is being tested?
- INT-1B3
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 18 Dec 2020to 24 Mar 2023
- 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
- Patient provided a signed written informed consent before any screening procedure
- Patient is male or female, ≥18 years of age (adult patients)
- Patient with histologically or cytologically confirmed advanced and/or metastatic solid tumor, with progressive disease at baseline, for whom no standard treatment is available or who have declined standard therapy
- Patient with evaluable disease per RECIST v1.1, iRECIST
- Patient with a predicted life expectancy of > 12 weeks
- Patient with Eastern Cooperative Oncology Group performance status of grade 0 - 1
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- Patient with hemoglobin ≥ 9.0 g/dL, platelet count ≥ 75×109/L, and absolute neutrophil count ≥ 1.0×109/L
- Patient with adequate renal function
- Patient with adequate liver function
- Patient with adequate coagulation tests
- Female patient of childbearing potential and males should use effective contraception
- Patient is able and willing to comply with the protocol and the restrictions and assessments therein
Who cannot join
- Patients on any other anti-cancer therapy, unless at least 4 weeks (or 5 half-lives, whichever is shorter), have elapsed since the last dose before the first administration of INT-1B3. At least 2 weeks should have elapsed since receiving non-palliative radiotherapy.
- Patient with known central nervous system (CNS) metastases, unless previously treated and well-controlled for at least 1 month (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart)
- Patient with concomitant second malignancies unless curatively treated at least 2 years before study entry with no additional therapy required or anticipated to be required during the study period
- Patient with major surgery within 5 weeks before initiating treatment or with minor surgical procedure within 7 days before initiating treatment
- Patient with active autoimmune disease or persistent immune-mediated toxicity caused by immune checkpoint inhibitor therapy of Grade ≥ 2, except for residual endocrinopathy adequately substituted, vitiligo, Type 1 diabetes mellitus or psoriasis not requiring systemic therapy (>10mg prednisone equivalent)
- Patient with toxicity (except for alopecia) related to prior anti-cancer therapy and/or surgery, unless the toxicity is either resolved, returned to baseline or grade 1
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- Patient with any active neuropathy > Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0)
- Patient with any condition requiring concurrent use of systemic immunosuppressants or corticosteroids at a daily dose > 10 mg prednisone equivalent or other immunosuppressive medications within 14 days of study medication administration
- Patient with evidence of active infection that requires systemic antibacterial, antiviral, or antifungal therapy ≤ 7 days before the first dose of study medication
- Patient with uncontrolled or significant cardiovascular disease
- Patient with known active or chronic hepatitis B or C (unless treated with no detectable virus)
- Patient with known history of exposure to human immunodeficiency virus (HIV)
- Patient with any known or underlying medical, psychiatric condition, and/or social situations that, in the opinion of the investigator, would limit compliance with study requirements
- Patient with history of allergy to the study medication or any of its excipients
- Patient that received packed red blood cells or platelet transfusion within 2 weeks of the first dose of study medication
- Female patient: pregnant or breastfeeding
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Belgium2 sites
GZA (Gasthuiszusters Antwerpen)
Antwerp
Institut Jules Bordet
Brussels, Wallonia, 1000
Netherlands2 sites
The Netherlands Cancer Institute
Amsterdam
Erasmus MC
Rotterdam
About this study
Official title: Phase I/Ib, Open-label, Multiple Ascending Dose, First-in-Human Study, to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of INT-1B3 in Patients With Advanced Solid Tumors
This is a 2 part, multi-center, open-label, First-in-Human clinical study to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of INT-1B3 in the treatment of patients with advanced solid tumors.
Read the detailed description
The investigational medicinal product INT-1B3 is a lipid nanoparticle formulated microRNA (miR-193a-3p) mimic destined for therapeutic intervention in oncology. Preclinical work showed that INT-1B3 has a multi-target mechanism of action with an anti-proliferative, anti-metastatic, anti-migration, cell cycle disruption, induction of apoptosis effect and modulation on the tumor microenvironment leading to significant induction of T cell-mediated immune response.
The first part of the study (Phase I) is a dose-escalation phase to determine the maximal tolerated dose and the recommended Phase 2 dose, as well as the safety profile of INT-1B3 in patients with advanced malignancies.The subsequent expansion phase of the study (Phase Ib) will further explore safety, pharmacokinetics, pharmacodynamic responses, and antitumor activity of INT-1B3 in patients with selected cancer types treated at the recommended phase 2 dose.
- Conditions
- Solid Tumor
- Being tested
- INT-1B3
- Keywords
- MicroRNA, Solid Tumor, Lipid-nanoparticle
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INT-1B3Drug
60-min i.v. infusions twice per week in 21-day cycles
| Study group | Role | What they receive |
|---|---|---|
| Phase 1/1b | Experimental | Phase 1: dose escalation phase with a 'hybrid' 3+3 design in all-comers cancer patients. Approximately 30 patients will be included.
Phase 1b: dose expansion phase in selected tumor types at the recommended phase 2 dose. Approximately 50 patients will be included. Receives: Drug: INT-1B3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of treatment-related adverse events and serious adverse events
Incidence and severity of adverse events, serious adverse events, according to NCI-CTCAE criteria v 5.0, incidence of dose limiting toxicities (DLTs), adverse events leading to discontinuation and deaths
Measured: Up to 24 months
Recommended Phase 2 Dose of INT-1B3
Based on dose-limiting toxicities, the maximal tolerated dose and all other available safety, pharmacokinetic/pharmacodynamic data as assessed by the cohort review committee
Measured: Up to 24 months
Secondary outcomes (5)
Area under the curve
Area under the plasma concentration time curve of INT-1B3
Measured: Up to 24 months
Maximum plasma concentration
Highest observed plasma concentration of INT-1B3
Measured: Up to 24 months
Time of maximum plasma concentration
Time to reach highest observed plasma concentration of INT-1B3
Measured: Up to 24 months
Half-life
Plasma concentration half-life of INT-1B3
Measured: Up to 24 months
Objective response rate of INT-1B3
Objective response rate according to standard criteria by RECIST1.1
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2020
- Study start18 Dec 2020
- Primary completion24 Mar 2023
- Study completion24 Mar 2023
Why it stopped: insufficient funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- InteRNA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Roel Schaapveld, PhD, Study director, InteRNA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04675996
- Sponsor's protocol ID
- INT1B3-CLIN-101
- Status last verified
- Feb 2024
- First submitted
- 8 Dec 2020
- Last updated
- 8 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/Ib, Open-label, Multiple Ascending Dose, First-in-Human Study, to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of INT-1B3 in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT04675996
- Acronym / sponsor ID
- INT1B3-CLIN-101
- Conditions
- Solid Tumor
- Keywords
- MicroRNA, Solid Tumor, Lipid-nanoparticle
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: insufficient funding
- Enrolment
- 25 participants (actual)
- Lead sponsor
- InteRNAIndustry (pharma, biotech, devices)
- Study start
- 18 Dec 2020 (actual)
- Primary completion
- 24 Mar 2023 (actual)
- Study completion
- 24 Mar 2023 (actual)
- First posted
- 19 Dec 2020 (actual)
- 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.
This is a 2 part, multi-center, open-label, First-in-Human clinical study to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of INT-1B3 in the treatment of patients with advanced solid tumors.
Detailed description
The investigational medicinal product INT-1B3 is a lipid nanoparticle formulated microRNA (miR-193a-3p) mimic destined for therapeutic intervention in oncology. Preclinical work showed that INT-1B3 has a multi-target mechanism of action with an anti-proliferative, anti-metastatic, anti-migration, cell cycle disruption, induction of apoptosis effect and modulation on the tumor microenvironment leading to significant induction of T cell-mediated immune response.
The first part of the study (Phase I) is a dose-escalation phase to determine the maximal tolerated dose and the recommended Phase 2 dose, as well as the safety profile of INT-1B3 in patients with advanced malignancies.The subsequent expansion phase of the study (Phase Ib) will further explore safety, pharmacokinetics, pharmacodynamic responses, and antitumor activity of INT-1B3 in patients with selected cancer types treated at the recommended phase 2 dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase 1/1b | Experimental | Drug: INT-1B3Phase 1: dose escalation phase with a 'hybrid' 3+3 design in all-comers cancer patients. Approximately 30 patients will be included. Phase 1b: dose expansion phase in selected tumor types at the recommended phase 2 dose. Approximately 50 patients will be included. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patient provided a signed written informed consent before any screening procedure
- Patient is male or female, ≥18 years of age (adult patients)
- Patient with histologically or cytologically confirmed advanced and/or metastatic solid tumor, with progressive disease at baseline, for whom no standard treatment is available or who have declined standard therapy
- Patient with evaluable disease per RECIST v1.1, iRECIST
- Patient with a predicted life expectancy of > 12 weeks
Key exclusion criteria (16 listed)
- Patients on any other anti-cancer therapy, unless at least 4 weeks (or 5 half-lives, whichever is shorter), have elapsed since the last dose before the first administration of INT-1B3. At least 2 weeks should have elapsed since receiving non-palliative radiotherapy.
- Patient with known central nervous system (CNS) metastases, unless previously treated and well-controlled for at least 1 month (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart)
- Patient with concomitant second malignancies unless curatively treated at least 2 years before study entry with no additional therapy required or anticipated to be required during the study period
- Patient with major surgery within 5 weeks before initiating treatment or with minor surgical procedure within 7 days before initiating treatment
- Patient with active autoimmune disease or persistent immune-mediated toxicity caused by immune checkpoint inhibitor therapy of Grade ≥ 2, except for residual endocrinopathy adequately substituted, vitiligo, Type 1 diabetes mellitus or psoriasis not requiring systemic therapy (>10mg prednisone equivalent)
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 |
|---|---|---|
| INT-1B360-min i.v. infusions twice per week in 21-day cycles | Drug | Phase 1/1b |
Primary outcome
Incidence and severity of treatment-related adverse events and serious adverse events
Time frame: Up to 24 months
Incidence and severity of adverse events, serious adverse events, according to NCI-CTCAE criteria v 5.0, incidence of dose limiting toxicities (DLTs), adverse events leading to discontinuation and deaths
Recommended Phase 2 Dose of INT-1B3
Time frame: Up to 24 months
Based on dose-limiting toxicities, the maximal tolerated dose and all other available safety, pharmacokinetic/pharmacodynamic data as assessed by the cohort review committee
5 secondary outcomes
Area under the curve
Time frame: Up to 24 months
Maximum plasma concentration
Time frame: Up to 24 months
Time of maximum plasma concentration
Time frame: Up to 24 months
Half-life
Time frame: Up to 24 months
Objective response rate of INT-1B3
Time frame: Up to 24 months
Results and safety
The study was stopped early (reason given: insufficient funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2024.
- Individual participant dataSharing planned: No
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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.
Roel Schaapveld, PhD study director
InteRNA
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing INT-1B3 in people with Solid Tumor, run by InteRNA at 4 sites in 2 countries.
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 12 inclusion and 16 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: stopped early, as of the sponsor's last update on 8 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Belgium, Netherlands. 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 was stopped early (reason given: insufficient funding). Results are not available in the source record.
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?
Incidence and severity of treatment-related adverse events and serious adverse events (time frame: Up to 24 months). 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?
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 8 Feb 2024.