Combination of Interferon-gamma and Nivolumab for Advanced Solid Tumors

NCT02614456 | Completed Phase 1 DMC

• 1 other identifier: GU-084
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I study of combination immunotherapy with IFN-γ and the PD-1 inhibitor nivolumab in patients with advanced solid tumors who have progressed on at least one prior systemic therapy, which may include prior immunotherapy.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Number of participants with treatment-related adverse events as assesses by CTCAE version 4.03.

  58 weeks

• Determine the recommended phase 2 dose (RP2D) based on Dose limiting toxicities

  6 weeks

Secondary Outcomes (9)

• To evaluate the investigator assessed ORR using standard response evaluation criteria in solid tumors (RECIST) version 1.1 for metastatic renal cell carcinoma.

  2 years

• To evaluate the investigator assessed ORR using standard response evaluation criteria in solid tumors (RECIST) version 1.1 for metastatic urothelial cancer.

  2 years

• To evaluate median progression free survival (PFS) using Kaplan-Meier curves for metastatic renal cell carcinoma.

  2 years

• To evaluate median progression free survival (PFS) using Kaplan-Meier curves for metastatic urothelial cancer.

  2 years

• To evaluate median overall survival (OS) using Kaplan-Meier curves for metastatic renal cell carcinoma.

  2 years

Study Arms (1)

Interferon-gamma and nivolumab

EXPERIMENTAL

Interferon-gamma (IFN-γ): starting dose 50 mcg/m2 subcutaneously Nivolumab: 3 mg/kg intravenously Induction phase: IFN-γ every other day alone for 1 week Combination phase: IFN-γ every other day \& Nivolumab every 2 weeks for 3 months Single agent phase: Nivolumab every 3 weeks up to 1 year

Drug: interferon-gamma and nivolumab

Interventions

interferon-gamma and nivolumab DRUG

Interferon-gamma and nivolumab

Eligibility Criteria

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

You may qualify if:

• Patients must have a histologically or cytologically confirmed metastatic solid tumor that has shown clinical or pre-clinical evidence of responding to anti-PD-1 therapy or the capacity to up-regulate PD-L1. These tumor types may include but may not be limited to: RCC, UC, melanoma, non small cell lung cancer (NSCLC), small cell lung cancer, squamous cell cancer of the head and neck (SCCHN), ovarian carcinoma, triple negative breast cancer, gastric cancer, microsatellite instability expressing (MSI-high) colon cancer, hepatocellular carcinoma, mesothelioma, gastrointestinal stromal tumors, endometrial carcinoma, liposarcomas, chondrosarcomas, and uterine sarcomas. Patients with solid tumor types not listed above may be enrolled at the discretion of the Principal Investigator.
• All patients must have received at least one line of systemic therapy in the metastatic setting. Prior immunotherapy is allowed, including prior treatment with nivolumab or another PD-1 inhibitor, as long as the reason for discontinuation of a prior PD-1 inhibitor was not for drug-related toxicity.
• Patients must have measurable disease per RECIST criteria v. 1.1 as described in detail in section 11.0.
• Patients must have a site of disease that is amenable to pretreatment and on-treatment core biopies. At least 3 formalin fixed, paraffin embedded (FFPE) slides at five microns each may be collected at each biopsy. Determination of tissue accessibility and quantity will be made by the consenting clinician. Patients must consent to the two study-required biopsy procedures.
• Age \> 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Patients must have normal organ and marrow function as defined below:
• Absolute neutrophil count \> 1,500/mcL
• Platelets \> 100,000/mcL
• Total bilirubin \< 1.5 times the upper limit of normal (ULN), except patients with Gilbert's syndrome in whom total bilirubin must be \<3.0 mg/dL
• AST/ALT (SGOT/SGPT) \< 3 times institutional normal limits
• Creatinine \< 1.5 times the ULN OR Creatinine clearance \> 40 mL/min (as measured or calculated by Cockroft-Gault formula)
• Ability to understand and willingness to sign a written informed consent and HIPAA consent document.

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study.
• Patients may not have any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids or immunosuppressive medications, except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo, type I diabetes mellitus, or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll.
• Any condition requiring systemic treatment with corticosteroids (\> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled or topical steroids and adrenal replacement steroid doses \> 10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease.
• Patients may not be receiving any other investigational agents.
• Patients with known active or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. Asymptomatic, treated, and/or stable brain metastases, as measured by subsequent radiologic evaluations at least two months apart, are permitted.
• History of allergic reactions attributed to compound of similar chemical or biologic composition to the agent(s) used in this study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension or psychiatric illness/social situations that would limit compliance with study requirements.
• Known human immunodeficiency virus (HIV) positive or history of acquired immune deficiency syndrome (AIDS) or AIDS-defining illness.
• Known current or a history of hepatitis B or C virus, including chronic and dormant states, unless disease has been treated and confirmed cleared.
• Any medical condition that in the investigator's opinion could interfere with interpretation of study or toxicity, or increase the risk to the patient related to potential toxicity.
• Major surgery within 4 weeks of initiation of study drug.
• Pregnant or breast feeding. Refer to section 4.4 for further detail.
• A second invasive malignancy requiring active treatment.

Sponsors & Collaborators

• Fox Chase Cancer Center: lead
• Horizon Pharma Ireland, Ltd., Dublin Ireland: collaborator

Study Sites (1)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Related Publications (1)

• Zibelman M, MacFarlane AW 4th, Costello K, McGowan T, O'Neill J, Kokate R, Borghaei H, Denlinger CS, Dotan E, Geynisman DM, Jain A, Martin L, Obeid E, Devarajan K, Ruth K, Alpaugh RK, Dulaimi EA, Cukierman E, Einarson M, Campbell KS, Plimack ER. A phase 1 study of nivolumab in combination with interferon-gamma for patients with advanced solid tumors. Nat Commun. 2023 Jul 27;14(1):4513. doi: 10.1038/s41467-023-40028-z.

  PMID: 37500647 DERIVED

MeSH Terms

Interventions

Interferon-gamma; Nivolumab

Intervention Hierarchy (Ancestors)

Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Macrophage-Activating Factors; Lymphokines; Proteins; Biological Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Study Officials

• Matthew Zibelman, MD

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 23, 2015
• First Posted: November 25, 2015
• Study Start: December 11, 2015
• Primary Completion: June 12, 2019
• Study Completion: June 12, 2019
• Last Updated: November 29, 2019

Record last verified: 2019-11

Locations

US (1)