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

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02452268
Collaborator
(none)
74
Enrollment
7
Locations
2
Arms
58
Actual Duration (Months)
10.6
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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
Phase 1

Study Design

Study Type:
Interventional
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 :
Mar 7, 2022
Actual Study Completion Date :
Mar 7, 2022

Arms and Interventions

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 Names:
  • 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

    Primary Outcome Measures

    1. Assess the dose-limiting toxicity of the single agent NIZ985 and the combination of PDR001 [28 days]

    Secondary Outcome Measures

    1. Determine the maximum tolerated dose (MTD) of hetIL-15 as determined by DLTs during Cycle 1. [28 days]

    2. Determine the pharmacokinetic (PK) profile of hetIL-15, including T½ [28 days]

    3. Determine the pharmacokinetic (PK) profile of hetIL-15, including Cmax. [28 Days]

    4. Determine the preliminary anti-tumor activity of hetIL-15 [8 weeks]

      Best overall response (BOR) per RECIST and irRC

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    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).

    1. Recovered to ≤ grade 1 NCI CTCAE version 4.0 from toxicity of prior chemotherapy or biologic therapy administered more than 4 weeks earlier.

    2. 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.

    3. Age ≥18 years.

    4. ECOG performance status ≤1 (Karnofsky ≥70%).

    5. 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.

    1. DLCO/VA and FEV1 ≥ 50% of predicted on PFTs.

    2. Subjects with inactive central nervous system (CNS) metastasis are eligible..

    3. 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.

    4. Able to provide written informed consent.

    5. 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

    Locations

    Site City State Country Postal Code
    1 National Cancer Institute National Cancer Institute Bethesda Maryland United States 20892
    2 Washington University School of Medicine SC Saint Louis Missouri United States 63110
    3 The Ohio State University Comprehensive Cancer Center Columbus Ohio United States 43212
    4 Providence Portland Medical Center SC Portland Oregon United States 97123
    5 Huntsman Cancer Institute Salt Lake City Utah United States 84112
    6 Seattle Cancer Care Alliance Seattle Washington United States 98105
    7 University of Wisconsin Madison Wisconsin United States 53792

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT02452268
    Other Study ID Numbers:
    • CNIZ985X2102J
    • NIZ985X2102J
    First Posted:
    May 22, 2015
    Last Update Posted:
    Mar 23, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Neoplasm Metastasis
    Spartalizumab

    Study Results

    No Results Posted as of Mar 23, 2022