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A Phase I/Ib Study of NIZ985 in Combination With PDR001 in Adults With Metastatic Cancers

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ClinicalTrials.gov Identifier: NCT02452268
Recruitment Status : Completed
First Posted : May 22, 2015
Last Update Posted : March 23, 2022
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
Phase I/Ib multicenter clinical trial. Single agent dose escalation of NIZ985 followed by expansion. Second escalation of NIZ985 in combination with PDR001 followed by expansion

Condition or disease Intervention/treatment Phase
Metastatic and Advanced Solid Tumors Drug: NIZ985 Drug: PDR001 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 74 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of Subcutaneous Recombinant Human NIZ985 ((hetIL-15) (IL15/sIL-15Ra)) Alone and in Combination With PDR001 in Adults With Metastatic Cancers
Actual Study Start Date : May 8, 2017
Actual Primary Completion Date : March 7, 2022
Actual Study Completion Date : March 7, 2022

Arm Intervention/treatment
Experimental: NIZ985
  • Single treatment arm, dose escalation administered subcutaneously (SC) on MWF for 2 consecutive weeks.
  • Cycle length 28 days.
  • Occurrence of a dose-limiting toxicity (DLT) leads to the expansion to 6 subjects.
  • MTD is the dose prior to the dose level where ≥ 2/6 subjects have a DLT.
  • Following identification of the MTD / RDE, dose expansion will follow.
Drug: NIZ985
Subcutaneous administration of hetIL-15 three times a week for two consecutive weeks
Other Name: IL-15/sIL-15Ra, heterodimeric IL-15

Experimental: NIZ985 + PDR001
  • The phase Ib dose escalation portion of the study will consist of a fixed dose (400 mg, IV infusion, Q4W) of PDR001 and escalating doses of NIZ985 (hetIL-15) to evaluate safety, tolerability and determine the MTD and/or RDE of the combination to be used in expansion cohorts.
  • On days when PDR001 and NIZ985 are administered on the same day, PDR001 will be administered first. NIZ985 will be administered after the PDR001 infusion has been completed.
  • Information on the preparation and administration of PDR001 is found in the PDR001 pharmacy manual.
Drug: PDR001
• PDR001 is a human monoclonal antibody (MAb) administered day 1 of each cycle

Primary Outcome Measures :
  1. Assess the dose-limiting toxicity of the single agent NIZ985 and the combination of PDR001 [ Time Frame: 28 days ]

Secondary Outcome Measures :
  1. Determine the maximum tolerated dose (MTD) of hetIL-15 as determined by DLTs during Cycle 1. [ Time Frame: 28 days ]
  2. Determine the pharmacokinetic (PK) profile of hetIL-15, including T½ [ Time Frame: 28 days ]
  3. Determine the pharmacokinetic (PK) profile of hetIL-15, including Cmax. [ Time Frame: 28 Days ]
  4. Determine the preliminary anti-tumor activity of hetIL-15 [ Time Frame: 8 weeks ]
    Best overall response (BOR) per RECIST and irRC

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histologically confirmed solid tumor malignancy that is metastatic or unresectable and have progressed on at least 1 prior therapy and for whom standard curative or palliative measures do not exist or are associated with minimal subject survival benefit.

    Evaluable or measurable disease, defined as by Response Evaluation Criteria in Solid Tumors (RECIST).

  2. Recovered to ≤ grade 1 NCI CTCAE version 4.0 from toxicity of prior chemotherapy or biologic therapy administered more than 4 weeks earlier.
  3. Subjects on bisphosphonates for any cancer or on hormone therapy for prostate cancer may continue this therapy. However, subjects with prostate cancer must have confirmed metastatic disease that has progressed despite hormonal therapy producing castrate levels of testosterone.
  4. Age ≥18 years.
  5. ECOG performance status ≤1 (Karnofsky ≥70%).
  6. Normal organ and marrow function:

    • leukocytes ≥3,000/mcL
    • absolute neutrophil count (ANC) ≥1,500/mcL
    • platelets ≥100,000/mcL
    • total bilirubin within normal institutional limits
    • AST/ALT ≤2.5 × ULN
    • creatinine <1.5 × institutional ULN OR
    • creatinine clearance ≥60 mL/min/1.73 m2 for subjects with serum creatinine levels >1.5 × higher than ULN.
  7. DLCO/VA and FEV1 ≥ 50% of predicted on PFTs.
  8. Subjects with inactive central nervous system (CNS) metastasis are eligible..
  9. Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, during the treatment portion of the study and for 4 months after completion of hetIL-15 administration.
  10. Able to provide written informed consent.
  11. Life expectancy > 3 months.

Exclusion Criteria:

  1. Prior IL-15 treatment or cytotoxic therapy, immunotherapy, radiotherapy, major surgery, antitumor vaccines or monoclonal antibodies in the 4 weeks prior or for checkpoint inhibitors such as anti-CTLA-4 or anti PD1/PD-L1 or nitrosoureas or mitomycin C for 6 weeks prior to C1D1.
  2. Primary brain cancers or active CNS metastases should be excluded from this clinical trial
  3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to hetIL-15.
  4. Concurrent anticancer therapy (including other investigational agents) with the exception of hormone therapy for prostate cancer.
  5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, cognitive impairment, active substance abuse, or psychiatric illness/social situations that, in the view of the Investigator, would preclude safe treatment or the ability to give informed consent and limit compliance with study requirements.
  6. HIV positive patients.
  7. Positive hepatitis B or C serology.
  8. History of severe asthma or absolute requirement for chronic inhaled corticosteroid medications.
  9. History of autoimmune disease, with the exception of an autoimmune event associated with prior ipilimumab (anti-CTLA-4) therapy that has been completely resolved for more than 4 weeks prior to C1D1.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02452268

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United States, Maryland
National Cancer Institute National Cancer Institute
Bethesda, Maryland, United States, 20892
United States, Missouri
Washington University School of Medicine SC
Saint Louis, Missouri, United States, 63110
United States, Ohio
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43212
United States, Oregon
Providence Portland Medical Center SC
Portland, Oregon, United States, 97123
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98105
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Novartis Pharmaceuticals
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02452268    
Other Study ID Numbers: CNIZ985X2102J
NIZ985X2102J ( Other Identifier: Novartis )
First Posted: May 22, 2015    Key Record Dates
Last Update Posted: March 23, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents