A Phase I/Ib Study of NIZ985 Alone and in Combination With Spartalizumab

Stopped early · Phase 1

Conditions studied: In Escalation: All Patients With Solid Tumors and Lymphoma, In Expansion: Melanoma, Non-small Cell Lung Cancer

In brief

The purpose of this phase I/Ib study was to determine the safety profile of NIZ985 (new formulation), and if it could be safely combined with spartalizumab or tislelizumab and to determine the appropriate dose and schedule for further study. Moreover, the study characterized the pharmacokinetic profiles of NIZ985 as a single agent and in combination with spartalizumab or tislelizumab and identified preliminary anti-tumor activity.

Key facts

Study ID

NCT04261439

Run by

Novartis Pharmaceuticals

People needed

60

Starts

2020-02-27

Expected to finish

2023-12-27

Last updated by the study team

2025-05-06

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Signed informed consent must be obtained prior to participation in the study.
• Male or female patients ≥ 18 years of age
• Histologically confirmed and documented advanced solid tumors and lymphoma (includes locally advanced malignancies that are not curable by surgery or radiotherapy, and those with metastatic disease) with documented progression following standard therapy, and for whom, no standard therapy is available, tolerated or appropriate. Disease must be measurable as determined by RECIST 1.1 (refer to Appendix 1) or Cheson et al (2014) (refer to Appendix 6).
• Escalation: Patients previously treated with CPI (anti PD-1/PD-L1 and/or anti CTLA-4) who have previously responded and progressed at any time prior to enrollment. Previous response is an initial radiographic CR/PR (a confirmatory scan is not required). If the most recent regimen included CPI, patients with SD lasting ≥ 6 months are also eligible.
• Expansion in melanoma: Patients with cutaneous melanoma previously treated with CPI (anti PD 1/ PD-L1 and/or anti CTLA-4) who have previously responded and progressed at any time prior to enrollment. Previous response is radiographic CR/PR (a confirmatory scan is not required). If the most recent regimen included CPI, patients with SD lasting ≥ 6 months are also eligible.
• Expansion in NSCLC: Patients with locally advanced or unresectable NSCLC who have been treated with up to 2 prior lines of therapies, at least one of which was a CPI-containing regimen (anti PD 1/ PD-L1 and/or anti CTLA-4). Patients must have previously responded to CPI and progressed at any time prior to enrollment. Previous response is radiographic CR/PR (a confirmatory scan is not required). If the most recent regimen included CPI, patients with SD lasting ≥ 6 months are also eligible. Patients with actionable mutations will be excluded.
• Patients must be willing and able to comply with the protocol for the duration of the study
• Patients must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at screening and during therapy on the study.
• ECOG performance status ≤1 and in the opinion of the investigator, likely to complete at least 28 days of treatment.

You may not qualify if…

• Patients that have received any prior IL-15 treatment.
• History of severe hypersensitivity reactions to any ingredient of study drug(s) and other mAbs and/or their excipients. In addition, patients with a history of immune mediated toxicities from CPI that led to permanent discontinuation of CPI treatment will be excluded.
• 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.
• 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.
• 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.
• 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:
• Absolute neutrophil count (ANC) <1.0 x 109/L
• Platelets <75 x 109/L
• Hemoglobin (Hgb) < 9 g/dL
• Serum creatinine > 1.5 x ULN or creatinine clearance < 60mL/min using Cockcroft-Gault formula (See Appendix 3)
• Total bilirubin > 1.5 x ULN, (except for patients with Gilbert's syndrome > 3.0 x ULN or direct bilirubin > 1.5 x ULN)
• Aspartate transaminase (AST) > 3 x ULN
• Alanine transaminase (ALT) > 3x ULN
• Serum electrolytes ≥ grade 2 despite adequate supplementation.
• Impaired cardiovascular function or clinically significant cardiovascular disease, including any of the following:
• Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA Grade ≥ 2), uncontrolled hypertension or clinically significant arrhythmia
• QTcF >470 msec on screening ECG or congenital long QT syndrome
• Acute myocardial infarction or unstable angina < 3 months prior to study entry
• Infection(s):
• HIV infection
• 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.
• Documented infection. Patients requiring systemic antibiotics for infection must have completed treatment before screening is initiated.
• 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.
• History of or current interstitial lung disease or pneumonitis grade ≥ 2.
• 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 study treatment, patients enrolled in the expansion must have remaining measurable disease that has not been irradiated.

Where it is running

• City of Hope National Medical — Duarte, California, United States
• Moores UCSD Cancer Center — La Jolla, California, United States
• Novartis Investigative Site — Leuven, Belgium
• Novartis Investigative Site — Essen, Germany
• Novartis Investigative Site — Naples, Italy
• Novartis Investigative Site — Chuo Ku, Tokyo, Japan
• Novartis Investigative Site — Barcelona, Catalonia, Spain
• Novartis Investigative Site — Madrid, Spain
• Novartis Investigative Site — Taipei, Taiwan

Full record on ClinicalTrials.gov

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