First-in-Human Study of INT-1B3 in Patients With Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT04675996
• Recruitment Status: Recruiting
• First Posted: December 19, 2020
• Last Update Posted: February 7, 2022
• Sponsor: InteRNA
• Information provided by (Responsible Party): InteRNA

Tracking Information

• First Submitted Date: December 8, 2020
• First Posted Date: December 19, 2020
• Last Update Posted Date: February 7, 2022
• Actual Study Start Date: December 18, 2020
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 15, 2020)

• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 15, 2020)

• Area under the curve [ Time Frame: Up to 24 months ]
  Area under the plasma concentration time curve of INT-1B3
• Maximum plasma concentration [ Time Frame: Up to 24 months ]
  Highest observed plasma concentration of INT-1B3
• Time of maximum plasma concentration [ Time Frame: Up to 24 months ]
  Time to reach highest observed plasma concentration of INT-1B3
• Half-life [ Time Frame: Up to 24 months ]
  Plasma concentration half-life of INT-1B3
• Objective response rate of INT-1B3 [ Time Frame: Up to 24 months ]
  Objective response rate according to standard criteria by RECIST1.1

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumor

Intervention

Drug: INT-1B3

60-min i.v. infusions twice per week in 21-day cycles

Study Arms

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.

Intervention: Drug: INT-1B3

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 15, 2020): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2024
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Karlijn Kroon, MD; +31 30 760 76 20; kroon@interna-technologies.com

• Listed Location Countries: Belgium, Netherlands

Administrative Information

• NCT Number: NCT04675996
• Other Study ID Numbers: INT1B3-CLIN-101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: InteRNA
• Original Responsible Party: Same as current
• Current Study Sponsor: InteRNA
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Roel Schaapveld, PhD; InteRNA

• PRS Account: InteRNA
• Verification Date: February 2022