Advanced solid tumors
Conditions
Interventions
The patients will receive INT-1B3 via an intravenous infusion for 120 minutes
per treatment. They will receive treatment once or twice per week, in 21-day
cycles.
Sponsors
InteRNA Technologies B.V.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Patient provided a signed written informed consent before any screening procedure 2. Patient with (a) lesion(s) assessable for sequential biopsies (baseline and on treatment) 3. Patient is male or female, >=18 years of age (adult patients) 4. 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 5. Patient with evaluable disease per RECIST v1.1, iRECIST or mRECIST (for HCC patients) 6. Patient with a predicted life expectancy of * 12 weeks 7. Patient with Eastern Cooperative Oncology Group (ECOG) performance status of Grade 0 - 1 8. Patient with hemoglobin >= 9.0 g/dL, platelet count >= 75×109/L, and absolute neutrophil count >= 1.0×109/L 9. Patient with adequate renal function (creatinine level within normal institutional limit defined as CrCl (corrected for body surface area (BSA)) or calculated creatinine clearance >= 50 mL/min/1.73 m2 (CKD-EPI calculation, see Appendix 11.1) 10. Patient with adequate liver function (aspartate transaminase and/or alanine transaminase <3 times institutional upper limit of normal (ULN) (or <= 5 times ULN for patients with liver metastases), total bilirubin <= 1.5 times ULN (or <= 3 x ULN for patients with Gilbert*s disease) 11. Patient with adequate coagulation tests: international normalized ratio or prothrombin time (PT) and activated partial thromboplastin time (aPTT) within 1.5 times ULN 12. Female patient of childbearing potential (defined as < 12 continuous months of amenorrhea with no identified cause other than menopause or not surgically sterile), must have a negative pregnancy test within 7 days before first administration of study medication and agree to use highly effective methods of contraception during the treatment until 60 days after the last administration of the study medication. Examples of highly effective contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. Hormonal contraceptive methods must be supplemented by a barrier method The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptom-thermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception 13. Male patients with a female partner of childbearing potential must agree to remain sexually abstinent or use adequate contraception (agreement to use a barrier method of contraception) during the treatment phase and 60 days after the last dose of the study medication. In addition, male patients must be willing to stop sperm donation during this time 14. Patient is able and willing to comply with the protocol and the restrictions and assessments therein. Additional inclusion criteria for dose-expansion phase (Phase Ib): 15. Patient with measurable disease per RECIST v1.1, iRECIST or mRECIST (for HCC) and at least 1 (additional) lesion accessible for sequential biopsies (baseline and on-treatment) 16. Patient ha
Exclusion criteria
Exclusion criteria: 1. Patient on any other anti-cancer therapy (cytotoxic, biologic or investigational agents), unless at least 4 weeks (or 5 half-lives, whichever is shorter, 6 weeks for mitomycin-C or nitrosoureas), 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. Chronic treatment with non-investigational gonadotropin-releasing hormone analogs or other hormonal or supportive care is permitted 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 (except for port-a-cath placement or biopsy) 5. Patient with active autoimmune disease or persistent immunemediated toxicity caused by immune checkpoint inhibitor therapy of grade >= 2 (patients with autoimmune-related hyperthyroidism, autoimmune-related hypothyroidism in remission, or with a stable dose of hormone-replacement, vitiligo, or psoriasis not requiring systemic therapy (>10mg prednisone equivalent) or controlled Type 1 diabetes mellitus, may be included) 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 (or are allowed according to other in/exclusion criteria) 7. Patient with any active neuropathy > Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events [CTCAE] v5.0) 8. Patient with a history of life-threatening (Grade 4) toxicity related to prior immune therapy or severe (Grade 3) toxicity that resulted in permanent discontinuation after rechallenge with immune therapy 9. 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 (permitted: premedication for i.v. contrast, treatment with a short course of steroids (< 5 days) up to 7 days before initiating study medication, and topical glucocorticoids, or steroid replacement doses for adrenal or pituitary insufficiency) 10. Patient with evidence of active infection that requires systemic antibacterial, antiviral, or antifungal therapy <= 7 days before the first dose of study medication 11. Patient with uncontrolled or significant cardiovascular disease including, but not limited to, any of the following: a) Left ventricular ejection fraction (LVEF) <= 50 % determined by echocardiogram or multi-gated acquisition (MUGA) scan b) High risk or uncontrolled clinically significant arrhythmias (such as atrial fibrillation and conduction disorders, ventricular tachycardia, ventricular fibrillation, or torsade de pointes) c) Treatment with drugs that are generally considered to have a high risk of causing torsade de pointes (it will b
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary End Points: • Incidence of adverse events (AEs) and serious AEs (SAEs) according to National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE) criteria v5.0, dose limiting toxicities (DLTs), AEs leading to discontinuation, deaths, electrocardiogram (ECG) abnormalities, and clinically significant laboratory abnormalities) • RP2D will be based on DLTs, the Maximum Tolerated Dose (MTD), and all available safety, PK/PD, and efficacy parameters | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary End Point: • The plasma concentration-time profile of INT-1B3 and the derived PK parameters (e.g., area under the curve [AUC], peak plasma concentration [Cmax], time to reach Cmax [tmax], terminal elimination rate constant [Lambda z]) • Objective response rate (ORR), duration of response (DOR), and clinical benefit rate (CBR), Progression Free Survival (PFS) Exploratory endpoints: • Correlation/measure of association of plasma PK and various PD biomarkers in the peripheral blood • Change from baseline in expression of target mRNAs in white blood cells and other pharmacodynamic biomarkers in blood samples at each dose level • Change from baseline in exploratory biomarkers in tumor biopsies and in plasma samples • Summary measures of antitumor activity by pre-treatment level of biomarkers of interest; correlation/measure of association of antitumor activity and change (or percent change) from baseline in biomarkers of interest • Anti-PEG antibodies • ORR, DOR, CBR, PFS (iRECIST) | — |
Countries
Netherlands
Outcome results
None listed