Phase I-II Study of Intratumoral Urelumab Combined With Nivolumab in Patients With Solid Tumors

NCT03792724 | Unknown Phase 1 FDA Drug

• 1 other identifier: INTRUST
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

Open label, phase I-II study to evaluate the safety and activity of intratumoral urelumab combined with systemic nivolumab in patients with advanced solid tumors. Serial tumor and blood samples will be obtained during the study to characterize the changes induced by treatment in the tumor microenvironment, as well as predictive biomarkers of response.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (3)

• Number of adverse events

  Number of adverse events

  27 months

• Recommended dose of intratumoral urelumab

  mg of intratumoral urelumab

  12 weeks

• Response rate

  Number of patients with partial response or complete response

  27 months

Secondary Outcomes (2)

• Overall survival (OS).

  27 months

• Progression-free survival (PFS)

  27 months

Study Arms (2)

Cohort A

EXPERIMENTAL

Three doses of intratumoral urelumab will be administered, every 4 weeks. after which Nivolumab will be given at a fixed dose of 240 mg for Cycle 2 and at a fixed dose of 480 mg every 4 weeks (Q4W) from Cycle 3 and beyond

Drug: Urelumab + Nivolumab

Cohort B

EXPERIMENTAL

Three doses of intratumoral urelumab will be administered, every 4 weeks. after which Nivolumab will be given at a fixed dose of 240 mg for Cycle 2 and at a fixed dose of 480 mg Q4W from Cycle 3 and beyond

Drug: Urelumab + Nivolumab

Interventions

Urelumab + Nivolumab DRUG

Treatment with intratumoral urelumab after which Nivolumab will be given.

Cohort A; Cohort B

Eligibility Criteria

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

You may qualify if:

• Written informed consent.
• Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing and other requirements of the study.
• Patients must present the following tumor types:
• For the phase I part, patients with any tumor type are eligible.
• For the phase II part, two cohorts will be established:
• i. Cohort A will include patients presenting tumor types with known sensitivity to Programmed cell death protein 1 (PD1)/ Programmed Death-ligand 1 (PDL1) blockade (e.g: melanoma, renal cancer, lung cancer, urothelial cancer, colorectal cancer presenting microsatellite instability (MSI), …). These patients must be naïve to PD1/PDL1 blockade.
• Patients must have received standard therapy, according to investigator´s criteria, or must be ineligible for standard therapy.
• Patients must present at least one tumor lesion that is amenable to perform sequential intratumoral therapy and biopsies.
• Measurable disease according to RECIST criteria. The measurable lesion(s) must be different than the lesion treated with intratumoral urelumab.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Life expectancy \>12 weeks.
• Adequate organ function defined by:
• 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).
• Hepatic: bilirubin \<1.5 times the upper limit of normality (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<3.0 x ULN (BR\< 3 x ULN for patients with Gilbert´s Syndrome).
• Renal: creatinine \<1.5 x ULN or estimated creatinine clearance \> 40 ml/min, using the Cokcroft-Gault formula.

You may not qualify if:

• 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.
• 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.
• 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.
• 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
• Active brain metastasis that may interfere with interpretation of results. Subjects with controlled metastasis will be allowed to enroll. Controlled brain metastases will be defined as no radiographic progression for at least 4 weeks following radiation and/or surgical treatment.
• Pregnant or breastfeeding patients.
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Routine testing is not required.
• History of allergy to study drug components or of severe hypersensitivity reactions to any monoclonal antibodies.
• Prisoners or subjects who are involuntarily incarcerated or who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
• 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.
• Known drug or alcohol abuse.

Sponsors & Collaborators

• Clinica Universidad de Navarra, Universidad de Navarra: lead

Study Sites (2)

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Clinica Universidad de Navarra

Madrid, 28022, Spain

Location

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MeSH Terms

Conditions

Neoplasms

Interventions

urelumab; Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Jose L Perz Gracia, MD PhD

CONTACT

+34948255400; jlgracias@unav.es

Mercedes Egaña, MD PhD

CONTACT

Study Design

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

Study Record Dates

• First Submitted: December 20, 2018
• First Posted: January 3, 2019
• Study Start: January 30, 2019
• Primary Completion: January 30, 2023
• Study Completion: January 30, 2023
• Last Updated: January 3, 2019

Record last verified: 2018-11

Locations

ES (2)