First-in-Human Study of INT-1B3 in Patients With Advanced Solid Tumors
Study Details
Study Description
Brief 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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
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
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Phase 1/1b 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. |
Drug: INT-1B3
60-min i.v. infusions twice per week in 21-day cycles
|
Outcome Measures
Primary Outcome Measures
- Incidence and severity of treatment-related adverse events and serious adverse events [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 [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
Secondary Outcome Measures
- Area under the curve [Up to 24 months]
Area under the plasma concentration time curve of INT-1B3
- Maximum plasma concentration [Up to 24 months]
Highest observed plasma concentration of INT-1B3
- Time of maximum plasma concentration [Up to 24 months]
Time to reach highest observed plasma concentration of INT-1B3
- Half-life [Up to 24 months]
Plasma concentration half-life of INT-1B3
- Objective response rate of INT-1B3 [Up to 24 months]
Objective response rate according to standard criteria by RECIST1.1
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patient provided a signed written informed consent before any screening procedure
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Patient is male or female, ≥18 years of age (adult patients)
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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
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Patient with evaluable disease per RECIST v1.1, iRECIST
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Patient with a predicted life expectancy of > 12 weeks
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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
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Patient with adequate renal function
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Patient with adequate liver function
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Patient with adequate coagulation tests
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Female patient of childbearing potential and males should use effective contraception
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Patient is able and willing to comply with the protocol and the restrictions and assessments therein
Exclusion Criteria:
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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.
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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)
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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
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Patient with major surgery within 5 weeks before initiating treatment or with minor surgical procedure within 7 days before initiating treatment
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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)
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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)
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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
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Patient with evidence of active infection that requires systemic antibacterial, antiviral, or antifungal therapy ≤ 7 days before the first dose of study medication
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Patient with uncontrolled or significant cardiovascular disease
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Patient with known active or chronic hepatitis B or C (unless treated with no detectable virus)
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Patient with known history of exposure to human immunodeficiency virus (HIV)
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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
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Patient with history of allergy to the study medication or any of its excipients
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Patient that received packed red blood cells or platelet transfusion within 2 weeks of the first dose of study medication
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Female patient: pregnant or breastfeeding
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Institut Jules Bordet | Brussels | Wallonie | Belgium | 1000 |
2 | GZA (Gasthuiszusters Antwerpen) | Antwerp | Belgium | ||
3 | The Netherlands Cancer Institute | Amsterdam | Netherlands | ||
4 | Erasmus MC | Rotterdam | Netherlands |
Sponsors and Collaborators
- InteRNA
Investigators
- Study Director: Roel Schaapveld, PhD, InteRNA
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- INT1B3-CLIN-101