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Patients that have received any prior IL-15 treatment
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History of severe hypersensitivity reactions to any ingredient of study drug(s) and other mAbs and/or their excipients
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Patients with primary CNS tumors are excluded. Presence of symptomatic CNS metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids 2 weeks prior to study entry. Patients with treated symptomatic brain metastases should be neurologically stable (for 4 weeks post-treatment and prior to study entry) and at a dose of 10 mg per day prednisone or equivalent for at least 2 weeks before administration of any study treatment
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Systemic chronic steroid therapy (> 10mg/day prednisone or equivalent) or any immunosuppressive therapy, other than replacement-dose steroids in the setting of adrenal insufficiency, within 7 days of the first dose of study treatment. Topical, inhaled, nasal and ophthalmic steroids are allowed
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Malignant disease, other than that being treated in this study, that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or other tumors that will not affect life expectancy
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Patients having out of range lab values during screening and before the first dose of study treatment. Out of range lab values are defined as
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Absolute neutrophil count (ANC) <1.0 x 109/L
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Platelets <75 x 109/L
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Hemoglobin (Hgb) < 9 g/dL
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Serum creatinine > 1.5 x ULN or creatinine clearance < 40mL/min using Cockcroft-Gault formula
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Total bilirubin > 1.5 x ULN, (except for patients with Gilbert's syndrome > 3.0 x ULN or direct bilirubin > 1.5 x ULN)
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Aspartate transaminase (AST) > 3 x ULN
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Alanine transaminase (ALT) > 3x ULN
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Serum electrolytes grade 2 despite adequate supplementation
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Impaired cardiovascular function or clinically significant cardiovascular disease, including any of the following
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Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA Grade 2), uncontrolled hypertension or clinically significant arrhythmia
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QTcF >470 msec on screening ECG or congenital long QT syndrome
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Acute myocardial infarction or unstable angina < 3 months prior to study entry
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Infection(s)
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HIV infection
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Active HBV or HCV infection (per institutional guidelines). Patients with chronic HBV or HCV disease that is controlled under antiviral therapy are allowed in expansion but not in escalation
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Infection requiring systemic antibiotic therapy. Patients requiring systemic antibiotics for infection must have completed treatment before screening is initiated
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Active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur may be considered. Patients previously exposed to CPI treatment who were adequately treated for skin rash or with replacement therapy for endocrinopathies should not be excluded
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History of or current interstitial lung disease or pneumonitis grade 2
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Radiotherapy within 2 weeks of the first dose of study drug, except for palliative radiotherapy to a limited field. To allow evaluation for response to treatment, patients enrolled in the expansion must have remaining measurable disease that has not been irradiated
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Treatment with cytotoxic or targeted antineoplastics within 3 weeks of initiation of study treatment. For cytotoxic agents that have major delayed toxicities, a washout period of one cycle is indicated (examples are nitrosoureas and mitomycin C which typically require a 6 week washout). Prior antibodies or immunotherapies require a 4 week washout. Ongoing bisphosphonate therapy and growth hormone-releasing hormone (GHRH) agonist therapy is allowed. Supportive therapy with denosumab is allowed. For patients with lymphoma, the following washout criteria may be used
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Systemic antineoplastic therapy (including cytotoxic chemotherapy, alfa-
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interferon, kinase inhibitors or other targeted small molecules, and toxin
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immunoconjugates) or any experimental therapy within 14 days or 5 half-lives
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whichever is shorter, before the first dose of study treatment
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\. Presence of Grade 2 toxicity according to National Cancer Institute (NCI)
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Common Terminology Criteria for Adverse Events (CTCAE v5.0), from prior cancer
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therapy with the exception of neuropathy (inclusion of patients with
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neuropathy of Grade 2 or less is permitted), ototoxicity, and alopecia
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\. Two weeks since major surgery treatment (mediastinoscopy, insertion of a
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central venous access device and insertion of a feeding tube are not
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considered major surgery)
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\. Use of any live vaccines against infectious diseases within 4 weeks of
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initiation of study treatment
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\. Use of hematopoietic growth factors or transfusion support 2 weeks prior
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to start of study treatment. If growth factors were initiated more than 2
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weeks prior to the first dose of study treatment and the patient is on a
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stable dose, they can be maintained
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\. Any medical condition that would, in the investigator's judgement
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prevent the patient's participation in the clinical study due to safety
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concerns, compliance with clinical study procedures, or interpretation of
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study results
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\. Pregnant or nursing (lactating) women
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\. Women of child-bearing potential, defined as all women physiologically
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capable of becoming pregnant, unless they are using highly effective methods
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of contraception while taking study medication and for 150 days after stopping
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medication. Highly effective methods of contraception methods include
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Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
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Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking investigational drug(s). In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
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Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject
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Use of oral (estrogen and progesterone), injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example, hormone vaginal ring or transdermal hormone contraception
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In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment
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NOTE: Women are considered post-menopausal and not of child bearing potential
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if they have had over 12 months of natural (spontaneous) amenorrhea with an
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appropriate clinical profile (e.g. age appropriate [generally age from 40 to
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years], history of vasomotor symptoms [e.g. hot flush]) in the absence of
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other medical justification or have had surgical bilateral oophorectomy (with
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or without hysterectomy), total hysterectomy or tubal ligation at least six
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weeks ago. In the case of oophorectomy alone, only when the reproductive
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status of the woman has been confirmed by follow up hormone level assessment
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is she considered not of child bearing potential
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\. A condom is required for all sexually active male participants to prevent
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them from fathering a child AND to prevent delivery of study treatment via
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seminal fluid to their partner. Sexually active males receiving NIZ985 as a
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single agent or in combination with Spartalizumab must use a condom during
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intercourse for 30 days after their last dose of NIZ985. In addition, male
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participants must not donate sperm for 30 days after the last dose of NIZ985
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Patients should not father a child during this post treatment period. A condom
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is required to be used also by vasectomized men as well as during intercourse
|
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with a male partner in order to prevent delivery of the drug via semen
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