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
Overview
- Phase
- Phase 1
- Intervention
- INT-1B3
- Conditions
- Solid Tumor
- Sponsor
- InteRNA
- Enrollment
- 25
- Locations
- 4
- Primary Endpoint
- Recommended Phase 2 Dose of INT-1B3
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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-1B
- •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
Arms & Interventions
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: INT-1B3
Outcomes
Primary Outcomes
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
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
Secondary Outcomes
- Maximum plasma concentration(Up to 24 months)
- Area under the curve(Up to 24 months)
- Half-life(Up to 24 months)
- Time of maximum plasma concentration(Up to 24 months)
- Objective response rate of INT-1B3(Up to 24 months)