- Signed and dated a REC-approved written informed consent form in accordance with
regulatory and institutional guidelines. Must be obtained before the performance of
any protocol-related procedures that are not part of normal patient care.
- Consent to provide tissue and blood samples for research
- Must be willing and able to comply with scheduled visits, treatment schedule,
laboratory tests, and other requirements of the study
- Histological confirmation of mesothelioma (any subtype, pleural or peritoneal).
- Must have received treatment with at least one prior line of treatment. Prior
maintenance therapy (e.g. avastin) is allowed and will not count as a line of therapy.
Prior lines of antineoplastic therapy, including chemotherapy, surgical resection of
lesions, radiation therapy, must be completed within 14 days of receiving nivolumab
- ECOG PS 0-1
- Age ≥18 years
- Expected survival of at least 12 weeks
- Radiologically assessable disease by modified RECIST (pleural mesothelioma) or RECIST
1.1 (non-pleural mesothelioma or where measurements for mRECIST cannot be obtained).
- Evidence of disease progression by CT scan
- Prior palliative radiotherapy must have been completed at least 14 days prior to study
- Screening laboratory values must meet the following criteria within 48 hours prior to
commencement of treatment:
i) White blood cells ≥ 2 x 10^9/L ii) Neutrophils ≥1.5 x 10^9/L iii) Platelets ≥ 100
X10^9/L iv) Haemoglobin ≥ 90 g/L v) Serum creatinine of ≤ 1.5 X ULN or creatinine
clearance (CrCl) > 50 mL/minute (using Cockcroft/Gault formula) vi) AST ≤ 3 X ULN vii)
ALT ≤ 3 X ULN viii) Total bilirubin ≤ 1.5 X ULN (except patients with Gilbert
Syndrome, who must have total bilirubin < 51.3 μmol/L) 2 x 10^9/L
- Reproductive status
1. Women of childbearing potential (WOCBP) must have a negative serum or urine
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) at
enrolment and within 24 hours prior to the start of study drug.
2. Women must not be breastfeeding.
3. WOCBP must agree to follow instructions for method(s) of contraception for the
duration of treatment with nivolumab plus 5 half-lives of nivolumab (5 x
half-life=125 days) plus 30 days (duration of ovulatory cycle) for a total of 5
months post- treatment completion.
4. 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 7 months after the last dose of investigational product. Women who are
not of childbearing potential (i.e., who are postmenopausal or surgically sterile
as well as azoospermic men do not require contraception.
- Expected surivial of at least 12 weeks.
- Target Disease Exceptions
1. Patients with untreated, symptomatic CNS metastases are excluded. Participants
are eligible if CNS metastases are adequately treated and participants are
neurologically returned to baseline (except for residual signs or symptoms
related to the CNS treatment) for at least 2 weeks prior to treatment assignment.
In addition, participants must be either off corticosteroids, or on a stable or
decreasing dose of <=10 mg daily prednisone (or equivalent) for at least 2 weeks
prior to treatment.
2. Patients with carcinomatous meningitis are excluded.
- Physical and Laboratory Test Findings
1. Known history of testing positive for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (AIDS).
2. Any positive test for hepatitis B virus or hepatitis C virus indicating acute or
- Allergies and Adverse Drug Reactions
a) History of severe hypersensitivity reactions to other monoclonal antibodies
- Medical History and Concurrent Diseases
1. Patients with active, known or suspected autoimmune disease.
2. Patients with a condition requiring systemic treatment with either
corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive
medications within 14 days of the first dose of study drug administration.
Inhaled or topical steroids and adrenal replacement steroid doses > 10 mg daily
prednisone or equivalent are permitted in the absence of active autoimmune
3. Other active malignancy requiring concurrent intervention.
4. Patients with previous malignancies (except non-melanoma skin cancers, and the
following in situ cancers: bladder, gastric, colon, endometrial,
cervical/dysplasia, melanoma or breast) are excluded unless a complete remission
was achieved at least 2 years prior to study entry AND no additional therapy is
required during the study period.
5. Any serious or uncontrolled medical disorder or active infection that, in the
opinion of the investigator, may increase the risk associated with study
participation, study drug administration, or would impair the ability of the
patient to receive protocol therapy.
6. All toxicities attributed to prior anti-cancer therapy other than alopecia and
fatigue not resolved to Grade 1 (NCI CTCAE version 4.03) or baseline before
administration of study drug.
7. Patients who have not recovered from the effects of major surgery or significant
traumatic injury at least 14 days before the first dose of study treatment.
8. Known alcohol or drug abuse.
9. Patients who have received prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2,
anti- CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody
or drug specifically targeting T-cell co-stimulation or checkpoint pathways) or
who have previously taken part in a randomised Bristol Myers Squibb (BMS)
clinical trial for nivolumab or ipilimumab including study CA209-743 (CheckMate
172) or in the CCTG trial of pembrolizumab (IND.227).