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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 : Recruiting
First Posted : May 22, 2015
Last Update Posted : October 2, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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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

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 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 : July 13, 2015
Estimated Primary Completion Date : December 30, 2019
Estimated Study Completion Date : December 31, 2019
Arms and Interventions
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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


Outcome Measures
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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. Characterize the pharmacodynamic effects of hetIL-15 on the percentages of circulating T-cell subsets (naive, central, or effector memory subsets) by flow cytometry and the plasma levels of pro-inflammatory cytokines. [ Time Frame: 28 days ]
  4. Determine the pharmacokinetic (PK) profile of hetIL-15, including Cmax. [ Time Frame: 28 Days ]
  5. Characterize the pharmacodynamic effects of hetIL-15 on the absolute numbers of circulating lymphocytes by flow cytometry and the plasma levels of pro-inflammatory cytokines. [ Time Frame: 28 Days ]
  6. Characterize the pharmacodynamic effects of hetIL-15 on the absolute numbers of circulating T-cell subsets (naive, central, or effector memory subsets) by flow cytometry and the plasma levels of pro-inflammatory cytokines. [ Time Frame: 28 days ]
  7. Characterize the pharmacodynamic effects of hetIL-15 on the percentages of circulating lymphocytes by flow cytometry and the plasma levels of pro-inflammatory cytokines. [ Time Frame: 28 days ]
  8. Determine the preliminary anti-tumor activity of hetIL-15 [ Time Frame: 8 weeks ]
    Best overall response (BOR) per RECIST and irRC


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

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.
Contacts and Locations
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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


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals

Locations
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United States, Maryland
Novartis Investigative Site Recruiting
Bethesda, Maryland, United States, 20892
Contact    +1 301 402 29 13      
Principal Investigator: Kevin Conlon         
United States, Missouri
Novartis Investigative Site Recruiting
Saint Louis, Missouri, United States, 63110
United States, Ohio
Novartis Investigative Site Recruiting
Columbus, Ohio, United States, 43212
United States, Oregon
Novartis Investigative Site Recruiting
Portland, Oregon, United States, 97123
United States, Utah
Novartis Investigative Site Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Keisa Hales    801-585-3453    keisa.hales@hci.utah.edu   
Principal Investigator: Sunil Sharma         
United States, Washington
Novartis Investigative Site Recruiting
Seattle, Washington, United States, 98105
Contact: Erin Shaw    206-288-2056    eshaw@seattlecca.org   
Principal Investigator: John Thompson         
United States, Wisconsin
Novartis Investigative Site Recruiting
Madison, Wisconsin, United States, 53792
Contact: Monika Stankiewicz       monika.stankiewicz@wisc.edu   
Principal Investigator: Douglas McNeel         
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02452268     History of Changes
Other Study ID Numbers: CNIZ985X2102J
NIZ985X2102J ( Other Identifier: Novartis )
First Posted: May 22, 2015    Key Record Dates
Last Update Posted: October 2, 2018
Last Verified: October 2018
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
Neoplasms
Pathologic Processes