Clinical Trials /

Phase I/Ib Study of NIS793 in Combination With PDR001 in Patients With Advanced Malignancies.

NCT02947165

Description:

To characterize the safety and tolerability of NIS793 as single agent and in combination with PDR001 and to identify recommended doses for future studies.

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase I/Ib Study of NIS793 in Combination With PDR001 in Patients With Advanced Malignancies.
  • Official Title: A Phase I/Ib, Open-label, Multi-center Dose Escalation Study of NIS793 in Combination With PDR001 in Adult Patients With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: CNIS793X2101
  • SECONDARY ID: 2016-003044-36
  • NCT ID: NCT02947165

Conditions

  • Breast Cancer
  • Lung Cancer
  • Hepatocellular Cancer
  • Colorectal Cancer
  • Pancreatic Cancer
  • Prostate Cancer
  • Renal Cancer

Interventions

DrugSynonymsArms
NIS793NIS793
PDR001NIS793 + PDR001

Purpose

To characterize the safety and tolerability of NIS793 as single agent and in combination with PDR001 and to identify recommended doses for future studies.

Trial Arms

NameTypeDescriptionInterventions
NIS793Experimental
  • NIS793
NIS793 + PDR001Experimental
  • NIS793
  • PDR001

Eligibility Criteria

        Inclusion Criteria:

          1. Written informed consent must be obtained prior to any screening procedures.

          2. Patient (male or female) ≥ 18 years of age.

          3. Escalation: Patients with advanced/metastatic solid tumors, with measurable or
             non-measurable disease as determined by RECIST version 1.1 who have progressed despite
             standard therapy or are intolerant of standard therapy, or for whom no standard
             therapy exists.

          4. Expansion: Patients with advanced/metastatic solid tumors, with at least one
             measurable lesion as determined by RECIST version 1.1, who have progressed despite
             standard therapy following their last prior therapy or are intolerant to standard
             therapy and fit into one of the following groups: Group 1: NSCLC; Group 2: TNBC; Group
             3: HCC; Group 4: MSS-CRC; Group 5: pancreatic, prostate and ccRCC.

          5. ECOG Performance Status ≤ 2.

          6. Patients must have a site of disease amenable to biopsy, and be a candidate for tumor
             biopsy. Patient must be willing to undergo a new tumor biopsy at screening, and during
             therapy on this study. Exceptions may be made on a case by case basis after documented
             discussion with Novartis.

        Exclusion Criteria:

          1. History of severe hypersensitivity reactions to study treatment ingredients or other
             monoclonal antibodies and components of study drug.

          2. Patients with active, known or suspected autoimmune disease. Note: Patients with
             vitiligo, type I diabetes mellitus, residual hypothyroidism only requiring hormone
             replacement, psoriasis not requiring systemic treatment, or conditions not expected to
             recur in the absence of an external trigger are permitted to enroll.

          3. HIV infection.

          4. Active HBV or HCV infection.

        Other protocol-defined inclusion/exclusion criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of DLTs, AEs, SAEs and dose reductions / interruptions for NIS793
Time Frame:Up to 90 days after end of treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Best overall response (BOR)
Time Frame:37 months
Safety Issue:
Description:Evaluate the anti-tumor activity per RECIST as well as per immune related Response Criteria (irRC) of NIS793 as single agent and in combination with PDR001 every 6 weeks (1 cycle = 3 weeks) from start of treatment until cycle 9 then every 9 weeks until end of treatment (if applicable).
Measure:Disease control rate (DCR)
Time Frame:37 months
Safety Issue:
Description:Evaluate the anti-tumor activity per RECIST as well as per immune related Response Criteria (irRC) of NIS793 as single agent and in combination with PDR001every 6 weeks (1 cycle = 3 weeks) from start of treatment until cycle 9 then every 9 weeks until end of treatment (if applicable).
Measure:Overall response rate (ORR)
Time Frame:37 months
Safety Issue:
Description:Evaluate the anti-tumor activity per RECIST as well as per immune related Response Criteria (irRC) of NIS793 as single agent and in combination with PDR001 every 6 weeks (1 cycle = 3 weeks) from start of treatment until cycle 9 then every 9 weeks until end of treatment (if applicable).
Measure:Progression free survival (PFS)
Time Frame:37 months
Safety Issue:
Description:Evaluate the anti-tumor activity per RECIST as well as per immune related Response Criteria (irRC) of NIS793 as single agent and in combination with PDR001 every 6 weeks from start of treatment until cycle 9 then every 9 weeks until end of treatment. During disease progression f/u, every 8 weeks for 40 weeks, then every 12 weeks.
Measure:Duration of response (DOR)
Time Frame:37 months
Safety Issue:
Description:Evaluate the anti-tumor activity per RECIST as well as per immune related Response Criteria (irRC) of NIS793 as single agent and in combination with PDR001 every 6 weeks (1 cycle = 3 weeks) from start of treatment until cycle 9 then every 9 weeks until end of treatment (if applicable).
Measure:Serum concentration-time profiles of NIS793 single agent and NIS793 in combination with PDR001
Time Frame:37 months
Safety Issue:
Description:Evaluate serum concentration of NIS793 and PDR001 every 3 weeks up to 24 weeks after start of treatment and at end of treatment.
Measure:Presence of anti-NIS793 and anti-PDR001 antibodies
Time Frame:37 months
Safety Issue:
Description:Assess the emergence of anti-NIS793 and anti-PDR001 antibodies every 3 weeks up to 24 weeks after start of treatment and at end of treatment.
Measure:Concentration of anti-NIS793 and anti-PDR001 antibodies
Time Frame:37 months
Safety Issue:
Description:Assess the concentration of anti-NIS793 and anti-PDR001 antibodies every 3 weeks up to 24 weeks after start of treatment and at end of treatment.
Measure:Area under the curve (AUC) for NIS793 single agent and NIS793 in combination with PDR001.
Time Frame:37 months
Safety Issue:
Description:Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.
Measure:Cmax for NIS793 single agent and NIS793 in combination with PDR001.
Time Frame:37 months
Safety Issue:
Description:Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.
Measure:Tmax for NIS793 single agent and NIS793 in combination with PDR001.
Time Frame:37 months
Safety Issue:
Description:Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.
Measure:Half life of NIS793 as single agent and in combination with PDR001.
Time Frame:37 months
Safety Issue:
Description:Characterize the pharmacokinetic properties of NIS793 given alone and in combination with PDR001.
Measure:Characterization of tumor infiltrating lymphocytes (TILs) by H&E
Time Frame:37 months
Safety Issue:
Description:Assess change from baseline of immune infiltrates in tumor biopsies after 3 cycles of treatment.
Measure:Characterization of tumor infiltrating lymphocytes by immunohistochemistry (CD8, FOXP3, PD-L1, TIM-3, LAG-3)
Time Frame:37 months
Safety Issue:
Description:Assess change from baseline in immunological markers in tumor biopsies after 3 cycles of treatment.

Details

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

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