History of Changes for Study: NCT04675996
First-in-Human Study of INT-1B3 in Patients With Advanced Solid Tumors
Latest version (submitted February 4, 2022) on
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Study Record Versions
Version A B Submitted Date Changes
1 December 15, 2020 None (earliest Version on record)
2 February 12, 2021 Recruitment Status, Study Status and Contacts/Locations
3 December 15, 2021 Contacts/Locations and Study Status
4 February 4, 2022 Study Status
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Study NCT04675996
Submitted Date:  December 15, 2020 (v1)

Open or close this module Study Identification
Unique Protocol ID: INT1B3-CLIN-101
Brief Title: First-in-Human Study of INT-1B3 in Patients With Advanced Solid Tumors
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
Secondary IDs:
Open or close this module Study Status
Record Verification: December 2020
Overall Status: Not yet recruiting
Study Start: December 2020
Primary Completion: December 2023 [Anticipated]
Study Completion: December 2024 [Anticipated]
First Submitted: December 8, 2020
First Submitted that
Met QC Criteria:
December 15, 2020
First Posted: December 19, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
December 15, 2020
Last Update Posted: December 19, 2020 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: InteRNA
Responsible Party: Sponsor
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module 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.
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.

Open or close this module Conditions
Conditions: Solid Tumor
Keywords: MicroRNA
Solid Tumor
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 80 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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
2. 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
Secondary Outcome Measures:
1. Area under the curve
[ Time Frame: Up to 24 months ]

Area under the plasma concentration time curve of INT-1B3
2. Maximum plasma concentration
[ Time Frame: Up to 24 months ]

Highest observed plasma concentration of INT-1B3
3. Time of maximum plasma concentration
[ Time Frame: Up to 24 months ]

Time to reach highest observed plasma concentration of INT-1B3
4. Half-life
[ Time Frame: Up to 24 months ]

Plasma concentration half-life of INT-1B3
5. Objective response rate of INT-1B3
[ Time Frame: Up to 24 months ]

Objective response rate according to standard criteria by RECIST1.1
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No

Inclusion Criteria:

  1. Patient provided a signed written informed consent before any screening procedure
  2. Patient is male or female, ≥18 years of age (adult patients)
  3. 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
  4. Patient with evaluable disease per RECIST v1.1, iRECIST
  5. Patient with a predicted life expectancy of > 12 weeks
  6. Patient with Eastern Cooperative Oncology Group performance status of grade 0 - 1
  7. Patient with hemoglobin ≥ 9.0 g/dL, platelet count ≥ 75×109/L, and absolute neutrophil count ≥ 1.0×109/L
  8. Patient with adequate renal function
  9. Patient with adequate liver function
  10. Patient with adequate coagulation tests
  11. Female patient of childbearing potential and males should use effective contraception
  12. Patient is able and willing to comply with the protocol and the restrictions and assessments therein

Exclusion Criteria:

  1. 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.
  2. 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)
  3. 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
  4. Patient with major surgery within 5 weeks before initiating treatment or with minor surgical procedure within 7 days before initiating treatment
  5. 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)
  6. 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
  7. Patient with any active neuropathy > Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0)
  8. 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
  9. Patient with evidence of active infection that requires systemic antibacterial, antiviral, or antifungal therapy ≤ 7 days before the first dose of study medication
  10. Patient with uncontrolled or significant cardiovascular disease
  11. Patient with known active or chronic hepatitis B or C (unless treated with no detectable virus)
  12. Patient with known history of exposure to human immunodeficiency virus (HIV)
  13. 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
  14. Patient with history of allergy to the study medication or any of its excipients
  15. Patient that received packed red blood cells or platelet transfusion within 2 weeks of the first dose of study medication
  16. Female patient: pregnant or breastfeeding
Open or close this module Contacts/Locations
Central Contact Person: Karlijn Kroon, MD
Telephone: +31645708338
Study Officials: Roel Schaapveld, PhD
Study Director
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Available IPD/Information:

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