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Study of the Safety and Efficacy of MIW815 With PDR001 in Patients With Advanced/Metastatic Solid Tumors or Lymphomas

NCT03172936

Description:

The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics and antitumor activity of MIW815 (ADU-S100) in combination with PDR001.

Related Conditions:
  • Lymphoma
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of the Safety and Efficacy of MIW815 With PDR001 to Patients With Advanced/Metastatic Solid Tumors or Lymphomas
  • Official Title: A Phase I, Open Label, Multicenter Study of the Safety and Efficacy of MIW815 (ADU-S100) Administered by Intratumoral Injection to Patients With Advanced/Metastatic Solid Tumors or Lymphomas

Clinical Trial IDs

  • ORG STUDY ID: CMIW815X2102J
  • SECONDARY ID: 2017-000707-25
  • NCT ID: NCT03172936

Conditions

  • Solid Tumors and Lymphomas

Interventions

DrugSynonymsArms
MIW815Dosing Schedule A
PDR001Dosing Schedule A

Purpose

The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics and antitumor activity of MIW815 (ADU-S100) in combination with PDR001.

Detailed Description

      This is a Phase Ib, multi-center, open-label study to characterize the safety, tolerability,
      pharmacokinetics, pharmacodynamics and preliminary antitumor activity of MIW815(ADU-S100) in
      combination with the PD-1 checkpoint inhibitor PDR001. Two different schedules will be
      explored in two dose escalation groups in accessible cutaneous or subcutaneous lesions, as
      well as an optional dose confirmation group exploring intratumoral injection of viscerally
      located lesions.

      Group A will include patients with accessible solid tumors and lymphomas. This group will
      receive a fixed dose of PDR001 i.v. on day 1 of every 28 day cycle and intratumoral
      injections of MIW815 (ADU-S100) on days 1, 8 and 15 of every 28 day cycle. Group B will
      include patients with accessible solid tumors and lymphomas. This group will receive a fixed
      dose of PDR001 i.v. on day 1 of every cycle and an intratumoral injection of MIW815
      (ADU-S100) on day 1 of every cycle.

      Once the dose and dose schedule has been confirmed, the dose expansion part of the study will
      open. The main purpose of the expansion part is to further assess the safety and
      tolerability, as well as preliminary anti-tumor activity, of the study treatment at the
      maximum tolerated dose and/or recommended dose for expansion. .
    

Trial Arms

NameTypeDescriptionInterventions
Dosing Schedule AExperimentalPatients will be treated with MIW815 (ADU-S100) via intratumoral injection for 3 weeks on followed by one week off in combination with a fixed intravenous dose of PDR001 given once per month
  • MIW815
  • PDR001
Dosing Schedule BExperimentalPatients will be treated with MIW815 (ADU-S100) via intratumoral injection given once a month in combination with a fixed intravenous dose of PDR001 given once per month
  • MIW815
  • PDR001

Eligibility Criteria

        Inclusion Criteria:

        ECOG ≤ 1 Willing to undergo tumor biopsies from injected and distal lesions

        Must have two biopsy accessible lesions:

        Exclusion Criteria:

        Symptomatic or untreated leptomeningeal disease. Presence of symptomatic central nervous
        system metastases Impaired cardiac function or clinically significant cardiac disease
        Active autoimmune disease or a documented history of autoimmune disease, except vitiligo or
        resolved childhood asthma/atopy.

        Active infection requiring systemic antibiotic therapy. Known history of human
        immunodeficiency virus infection. Active Epstein-Barr virus, hepatitis B virus or hepatitis
        C virus Malignant disease, other than that being treated in this study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose limiting toxicities (DLTs)
Time Frame:24 months
Safety Issue:
Description:A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment with the combination of MIW815 (ADU-S100) and PDR001

Secondary Outcome Measures

Measure:AUC last
Time Frame:36 months
Safety Issue:
Description:The area under the concentration (AUC) -time curve calculated to the last quantifiable concentration point (mass* time/volume)
Measure:AUC tau
Time Frame:36 months
Safety Issue:
Description:Area under the concentration-time curve calculated to the end of the dosing interval (tau) (mass* time/volume)
Measure:AUC inf
Time Frame:36 months
Safety Issue:
Description:The area under the concentration-time curve extrapolated to infinity (mass*time/volume)
Measure:Cmax
Time Frame:36 months
Safety Issue:
Description:The maximum observed concentration (Cmax) following dose administration (mass/volume)
Measure:Tmax
Time Frame:36 months
Safety Issue:
Description:The time to reach the maximum observed concentration (time)
Measure:Cmin
Time Frame:36 months
Safety Issue:
Description:Minimum observed plasma concentration (mass/volume)
Measure:Lambda_z
Time Frame:36 months
Safety Issue:
Description:Terminal elimination rate constant (1/time)
Measure:T1/2
Time Frame:36 months
Safety Issue:
Description:Elimination half-life, determined as 0.693/Lambda_z (time)
Measure:CL/F
Time Frame:36 months
Safety Issue:
Description:Apparent systemic clearance of drug from the plasma (volume x time -1)
Measure:Vz/F
Time Frame:36 months
Safety Issue:
Description:Apparent volume of distribution during the terminal elimination phase (volume)
Measure:Best overall response (BOR)
Time Frame:36 months
Safety Issue:
Description:Best overall response will be summarized with accompanying 90% exact binomial confidence interval.
Measure:Overall response rate (ORR)
Time Frame:36 months
Safety Issue:
Description:Overall response rate will be summarized with accompanying 90% exact binomial confidence interval.
Measure:Progression free survival (PFS)
Time Frame:36 months
Safety Issue:
Description:The survival function will be estimated using the Kaplan-Meier product limit method. Median duration, with a two-sided Brookmeyer-Crowley 90% confidence interval and Kaplan-Meier estimates of survival proportions will be provided at specified time points.
Measure:Disease control rate (DCR)
Time Frame:36 months
Safety Issue:
Description:The disease control rate is calculated as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease
Measure:Time to response (TTR)
Time Frame:36 months
Safety Issue:
Description:Kaplan-Meier estimates may be provided if sufficient numbers of patients respond.
Measure:Tumor infiltrating lymphocytes (TIL)
Time Frame:36 months
Safety Issue:
Description:Induction of TILs in the injected lesion (local PD effect) and in a non-injected lesion (distal PD effect) will be assessed using paired tumor samples at screening and on-treatment.
Measure:Cytokines
Time Frame:36 months
Safety Issue:
Description:Induction of cytokines in the injected lesion (local PD effect) and in a non-injected lesion (distal PD effect) will be assessed using paired tumor samples at screening and on-treatment.

Details

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

Trial Keywords

  • injected lesion
  • distal lesion
  • abscopal activity
  • intratumoral
  • checkpoint inhibitor
  • cyclic dinucleotide
  • programmed cell death

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