Isunakinra - a potent Interleukin-1 receptor inhibitor - will be given to patients with solid
tumors to determine safety and tolerability of three different doses. Isunakinra will then be
combined with a PD-(L)1 inhibitor. Pharmacokinetics and Pharmacodynamic effects of
monotherapy treatment as well as the combination will be evaluated.
1. Subjects must have:
- Metastatic or unresectable locally advanced malignant solid tumor.
- Histologic confirmation.
2. The study patients are required to have measurable disease by radiographic criteria
(RECIST 1.1) and irRC.
3. Prior therapy: Patients must have completed or had disease progression on at least one
prior line of disease-appropriate therapy for metastatic disease (with or without PD-1
inhibitors), with no available therapy likely to convey clinical benefit, or not be
candidates for therapy of proven efficacy for their disease.
4. There should be a minimum of 2 weeks from any prior chemotherapy, immunotherapy and/or
radiation and 4 weeks washout period for immunotherapy. Patients with prostate cancer
on hormone deprivation therapy may continue that therapy while on study.
5. Patients must have recovered (grade 1 or baseline) from any clinically significant
toxicity associated with prior therapy (for example, alopecia is not clinically
significant). Typically, this approximates 3-4 weeks for patients who most recently
received cytotoxic therapy, except for the nitrosoureas and mitomycin C, for which 6
weeks is needed for recovery.
6. Age ≥ 18 years. Because no dosing or adverse event data are currently available on the
use of this agent in patients < 18 years of age, children are excluded from this study
but will be eligible for future pediatric trials.
7. ECOG performance status ≤ 1
8. Patients must have normal organ and hematologic function as defined below:
- Serum creatinine ≤ 1.5 x upper limit of normal OR creatinine clearance and a 24-h
urine collection of ≥ 60 mL/min.
- ALT and AST ≤ 3x the upper limits of normal.
- Total bilirubin ≤ 1.5 x upper limit of normal OR in patients with Gilbert's
syndrome, a total bilirubin ≤ 3.0.
- Hematological eligibility parameters (within 16 days of starting therapy):
- Granulocyte count ≥ 1,500/mm3
- Platelet count ≥ 75.000/mm3
9. Patients must have baseline pulse oximetry > 90% on room air.
1. Pregnant women or women presently breast-feeding their children are excluded due to
unknown risks to a developing fetus or infant, confirmed by negative pre-treatment
serum pregnancy test.
2. Concurrent treatment for cancer, with specific exceptions noted in inclusion criteria.
3. Any significant disease that, in the opinion of the investigator, may impair the
patient's tolerance of study treatment.
4. Significant dementia, altered mental status, or any psychiatric condition that would
prohibit the understanding or rendering of informed consent.
5. Active autoimmune diseases requiring treatment. However, patients with vitiligo,
alopecia, or clinically stable autoimmune endocrine disease who are on appropriate
replacement therapy (if such therapy is indicated) are eligible.
6. Concurrent use of systemic steroids, except for physiologic doses of systemic steroid
replacement or local (topical, nasal, or inhaled) steroid use. Limited pharmacologic
doses of systemic steroids (e.g., in patients with exacerbations of reactive airway
disease or to prevent iv contrast allergic reaction or anaphylaxis in patients who
have known contrast allergies) are allowed.
7. Patients who are receiving any other investigational agents within 28 days before
start of study treatment.
8. Patients with untreated central nervous system metastases or local treatment of brain
metastases within the last 6 months. Patients with stable brain metastasis for 6
months post-intervention are eligible.
9. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to the agents used in study.
10. Serious or uncontrolled intercurrent illness including, but not limited to, ongoing or
active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of
the investigator, would limit compliance with study requirements.
11. HIV-positive patients are ineligible because of the potential for decreased immune
12. Patients unwilling to use adequate contraception (defined as hormonal or barrier
method or abstinence) prior to study entry are excluded. If the patient needs to be on
adequate contraception, contraception must start before study entry and continue for 3
months after completion of study therapy.