Clinical Trials /

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

NCT02452268

Description:

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

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase I/Ib Study of NIZ985 in Combination With PDR001 in Adults With Metastatic Cancers
  • 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

Clinical Trial IDs

  • ORG STUDY ID: CNIZ985X2102J
  • SECONDARY ID: NIZ985X2102J
  • NCT ID: NCT02452268

Conditions

  • Metastatic and Advanced Solid Tumors

Interventions

DrugSynonymsArms
NIZ985IL-15/sIL-15Ra, heterodimeric IL-15NIZ985
PDR001NIZ985 + PDR001

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
NIZ985ExperimentalSingle 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.
  • NIZ985
NIZ985 + PDR001ExperimentalThe 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.
  • PDR001

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Assess the dose-limiting toxicity of the single agent NIZ985 and the combination of PDR001
Time Frame:28 days
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Determine the maximum tolerated dose (MTD) of hetIL-15 as determined by DLTs during Cycle 1.
Time Frame:28 days
Safety Issue:
Description:
Measure:Determine the pharmacokinetic (PK) profile of hetIL-15, including T½
Time Frame:28 days
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Determine the pharmacokinetic (PK) profile of hetIL-15, including Cmax.
Time Frame:28 Days
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Determine the preliminary anti-tumor activity of hetIL-15
Time Frame:8 weeks
Safety Issue:
Description:Best overall response (BOR) per RECIST and irRC

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

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