IPINIVO - A Pharmacodynamics study of Nivolumab in Combination with Ipilimumab in Patients with Advanced or Metastatic Solid Tumours'

Phase 2

Completed

• Conditions: Advanced or Metastatic Solid Tumours; Cancer - Malignant melanoma; Cancer - Lung - Non small cell; Cancer - Hodgkin's; Cancer - Kidney; Cancer - Head and neck; Cancer - Bladder; Cancer - Prostate; Cancer - Bowel - Back passage (rectum) or large bowel (colon); Cancer - Brain

• Registration Number: ACTRN12617001059358
• Lead Sponsor: Clinical Network Services

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-07-20
• Study Completion: 2018-01-09
• Last Update Posted: 13 July 2020

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

1.Willing and able to give signed written informed consent.
2.Male or female subjects aged > 18 years.
3.Subjects must have a histologically or cytologically confirmed, metastatic or locally advanced solid tumor for which no standard therapy exists or standard therapy has failed.
4.Performance status score 0-1 (Eastern Cooperative Oncology Group Scale)
5.Estimated life expectancy > 3 months.
6.Subjects must have pretreatment clinical laboratory values meeting the following criteria during the Screening Phase (subjects may be retested during Screening Phase):
•Adequate hematological function defined by white blood cell count (WBC) > 3 x 109/L, absolute neutrophil count (ANC) > 1.5 x 109/L, lymphocyte count > 0.5 x 109/L, platelet count > 100 x 109/L, and hemoglobin > 9 g/dL (may be transfused). For subjects with gastric cancer only, acceptable parameters for WBC, ANC, and lymphocytes are as follows: WBC > 2 x 109/L, ANC > 1.0 x 109/L, and lymphocyte count > 0.5 x 109/L.
•Adequate hepatic function based by a total bilirubin level < 1.5 x the institutional upper limit of normal (IULN), and aspartate aminotransferase (AST) level < 2.5 x IULN, and an alanine aminotransferase (ALT) level < 2.5 x IULN. For subjects with documented metastatic disease to the liver, AST and ALT levels < 5 x IULN.
•Adequate renal function defined by an estimated clearance > 50 mL/min according to Cockcroft-Gault formula or measured 24-hour creatinine clearance (or local institutional standard method).
7.Effective contraception for both male and female subjects if risk of conception exists.
Note: Nivolumab and ipilimumab can cause fetal harm. Thus, women of childbearing potential and men must agree to use effective contraception, defined as 2 barrier methods, or 1 barrier method with an intrauterine device or use of oral female contraceptive. Subjects must confirm use of effective contraception at least 28 days before first study drug administration and for the duration of trial participation. Female subjects will be advised to maintain effective contraception for at least 5 months after the last treatment dose. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this trial, the treating physician should be informed immediately.

Exclusion Criteria

1.Prior therapy with any antibody/drug targeting T cell co-regulatory proteins (immune checkpoints), such as anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody.
2.Concurrent anticancer treatment (e.g., cytoreductive therapy, radiotherapy except for palliative bone-directed radiotherapy, immune therapy, or cytokine therapy except for erythropoietin) within 21 days or 5x (five times) their half-lives (whichever is shorter) before the first dose of trial treatment; major surgery within 28 days before start of trial treatment (excluding prior diagnostic biopsy); or use of hormonal agents within 7 days before start of trial treatment, except for subjects with castration-resistant prostate cancer (CRPC), who may remain on treatment with luteinizing hormone–releasing hormone agonists or antagonists.
Note: Subjects receiving bisphosphonate or denosumab are eligible provided that treatment was initiated equal to 14 days before first dose of treatment.
3.Use of any investigational drug within 21 days or 5x their half-lives (whichever is shorter) before the first dose of trial treatment.
4.Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs 14 days before initiation of trial treatment. Steroids with no or minimal systemic effect (topical, inhalation) are allowed.
Note: Use of inhaled or topical corticosteroid is permitted.
Note: Steroid pre-medication for radiographic imaging for dye allergies is permitted.
5.Rapidly progressive disease.
6.Active central nervous system metastases.
7.Receipt of any organ transplantation, including allogeneic stem-cell transplantation.
8.Significant acute or chronic infections, including:
•Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
•Positive test for hepatitis B virus (HBV) surface antigen and/or confirmatory hepatitis C virus (HCV) RNA (if anti-HCV antibody tested positive).
9.Active or history of any autoimmune disease (subjects with diabetes type 1, vitiligo, psoriasis, hypo-, or hyperthyroid disease not requiring immunosuppressive treatment are eligible) or immunodeficiencies.
10.Known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE grade equal to 3), any history of anaphylaxis, or uncontrolled asthma (i.e., equal to 3 features of partly controlled asthma).
11.Persisting toxicity related to prior therapy of NCI CTCAE grade greater than 1 severity. Sensory neuropathy of grade 2 is acceptable.
12.Pregnancy or breast feeding.
13.Known alcohol or drug abuse.
14.Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (less than 6 months before enrollment), myocardial infarction (less than 6 months before enrollment), unstable angina, congestive heart failure (New York Heart Association class is equal to II), or serious uncontrolled cardiac arrhythmia requiring medication.
15.All other significant diseases (e.g., inflammatory bowel disease) that, in the opinion of the investigator, might impair the subject’s tolerance of trial treatment.
16.Any psychiatric condition that would prohibit understanding or rendering of informed consent.
17.Legal incapacity or limited legal capacity.
18.Vaccination within 4 weeks of first dose of the combination nivolumab/ipilimumab and while on study except for administration of inactivated vaccines (e.g., inactiv

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To evaluate the change in Ki-67 expression in CD4+ peripheral blood T-cells as a pharmacodynamic biomarker for the effect of nivolumab in combination with ipilimumab on peripheral T-cells.[Change in Ki-67 expression from baseline in CD4+ peripheral blood T-cells at Cycle 1, Day 4 and Day 8 and from baseline to the end of the first 6-week cycle.]