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

NCT04675996 | Terminated Phase 1 DMC

• 1 other identifier: INT1B3-CLIN-101
• Study Type: interventional
• Target: 25
• Locations: 2 countries
• Sites: 4

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.

Conditions

Solid Tumor

Keywords

MicroRNA; Solid Tumor; Lipid-nanoparticle

Outcome Measures

Primary Outcomes (2)

• 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

  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

  Up to 24 months

Secondary Outcomes (5)

• Area under the curve

  Up to 24 months

• Maximum plasma concentration

  Up to 24 months

• Time of maximum plasma concentration

  Up to 24 months

• Half-life

  Up to 24 months

• Objective response rate of INT-1B3

  Up to 24 months

Study Arms (1)

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.

Drug: INT-1B3

Interventions

INT-1B3 DRUG

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

Phase 1/1b

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• InteRNA: lead

Study Sites (4)

Institut Jules Bordet

Brussels, Wallonia, 1000, Belgium

Location

GZA (Gasthuiszusters Antwerpen)

Antwerp, Belgium

Location

The Netherlands Cancer Institute

Amsterdam, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

Study Officials

• Roel Schaapveld, PhD

  InteRNA

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2020
• First Posted: December 19, 2020
• Study Start: December 18, 2020
• Primary Completion: March 24, 2023
• Study Completion: March 24, 2023
• Last Updated: February 8, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2); NL (2)