Advanced solid tumors
Conditions
Interventions
Product Name: Urelumab
Product Code: BMS-663513-01
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: URELUMAB
CAS Number: 934823-49-1
Concentration unit: mg/ml milligram(s)/millilitre
Co
Sponsors
Clínica Universidad de Navarra/Universidad de Navarra
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent. 2. Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing and other requirements of the study. 3. Patients must present the following tumor types: a. For the phase I part, patients with any tumor type are eligible. b. For the phase II part, two cohorts will be established: i. Cohort A will include patients presenting tumor types with low known sensitivity to PD1/PDL1 blockade (e.g: colorectal cancer -excluding tumors with known MSI-, sarcomas, prostate cancer, breast cancer …). These patients must be naïve to PD1/PDL1 blockade. ii. Cohort B will include patients with PD1/PDL1 sensitive tumors that have progressed following previous PD1/PDL1 blockade (e.g: melanoma, NSCLC, renal cancer, bladder cancer ..). Additional treatments may be administered between prior PD1/PDL1 blockade and inclusion in the study, but if administered immediately before a minimum wash-out period of four weeks must be observed between both treatments. The rationale to include such cohorts is to maximize the clinical significance of any response that is observed. 4. Patients must have received standard therapy, according to investigator´s criteria, or must be ineligible or refuse standard therapy. 5. Patients must present at least one tumor lesion that is amenable to perform sequential intratumoral therapy and biopsies. 6. Measurable disease according to RECIST criteria. The measurable lesion(s) must be different than the lesion treated with intratumoral urelumab. 7. There is no limit on previous treatment lines, as long as the other inclusion criteria are met. 8. ECOG performance status of 0-1. 9. Life expectancy >12 weeks. 10. Adequate organ function defined by: a. Bone Marrow Reserve: white blood cells (WBC): >2000/ mm3 absolute neutrophil count (ANC) >1500x 109/L; platelet count >100000/ mm3 100 x 109/L; hemoglobin > 9.0 g/dL). b. Hepatic: bilirubin 40 ml/min, using the Cokcroft-Gault formula. 11. Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab and urelumab to undergo five half-lives) after the last dose of investigational drug. 12. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of treatment 13. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product. Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception. 14. Patients must be at least 18 years old. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects
Exclusion criteria
Exclusion criteria: 1. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive the planned therapy or interfere with the interpretation of study results. Special care should be taken with conditions affecting the liver. 2. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. 3. The treatment wash-out period for other previous therapies, including radiation therapy will be determined by the investigators, depending on resolution of associated toxicity. Limited-field palliative radiotherapy will not require a wash-out period. If PD1/PDL1 blockade is the previous therapy, a minimum wash-out period of four weeks must be observed between both treatments. 4. Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease 5. Active brain metastasis that may interfere with interpretation of results. Subjects with controlled metastasis will be allowed to enrol. Controlled brain metastases will be defined as no radiographic progression for at least 4 weeks following radiation and/or surgical treatment. 6. Pregnant or breastfeeding patients. 7. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Routine testing is not required. 8. Positive tests for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating active or chronic infection. NOTE: subjects with positive hepatitis C antibody and negative quantitative hepatitis C by PCR are eligible. History of resolved hepatitis A virus infection is not an exclusion criteria. 9. History of allergy to study drug components or of severe hypersensitivity reactions to any monoclonal antibodies. 10. Prisoners or subjects who are involuntarily incarcerated or who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness. 11. Concomitant or prior malignancy that, in the opinion of the investigator can interfere with the results of the study, in the opinion of the investigator. 12. Known drug or alcohol abuse.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Phase I: to assess the safety and to establish the recommended dose of the combination of intratumoral urelumab administered in combination with systemic nivolumab in patients with advanced solid tumors. Three doses of intratumoral urelumab will be assessed, in combination with systemic nivolumab at standard doses. - Phase II: to detetermine the objective response rate of the recommended schedule determined by RECIST and immune response criteria.;Secondary Objective: - Tumor immune microenvironment changes in serial biopsies during treatment. - Tumor and peripheral blood biomarkers predictive of clinical activity, in baseline and follow-up samples. - Progression-free survival (PFS) and overall survival (OS). - Safety and tolerability of the combination. - Pharmacokinetics of urelumab administered intratumorally.;Primary end point(s): - Phase I: Criterios CTC (Common Toxicity criteria) V 4.0 - Phase II: Criterios RECIST;Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Molecular results of the study Survival variables Criterios CTC (Common Toxicity criteria) V 4.0 Pharmacokinetic results;Timepoint(s) of evaluation of this end point: 6 months | — |
Countries
Spain
Contacts
Public ContactUCEC
Clinica Universidad de Navarra
Outcome results
None listed