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

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ClinicalTrials.gov Identifier: NCT03172936
Recruitment Status : Recruiting
First Posted : June 1, 2017
Last Update Posted : August 24, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

Condition or disease Intervention/treatment Phase
Solid Tumors and Lymphomas Drug: MIW815 Biological: PDR001 Phase 1

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. .


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

The study is comprised of two treatment arms.

Group A will include patients with accessible solid tumors and lymphomas. This group will receive a fixed dose of PDR001 intravenous 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 intravenous on day 1 of every cycle and an intratumoral injection of MIW815 (ADU-S100) on day 1 of every cycle.

Once the maximum tolerated dose and/or recommended dose for expansion is determined, the expansion part of the study will open.

Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 8, 2017
Estimated Primary Completion Date : May 30, 2019
Estimated Study Completion Date : December 29, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Dosing Schedule A
Patients 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
Drug: MIW815
MIW 815 (ADU-S100) is a STING agonist

Biological: PDR001
PDR001 is an anti-PD-1 antibody

Experimental: Dosing Schedule B
Patients 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
Drug: MIW815
MIW 815 (ADU-S100) is a STING agonist

Biological: PDR001
PDR001 is an anti-PD-1 antibody




Primary Outcome Measures :
  1. Incidence of dose limiting toxicities (DLTs) [ Time Frame: 24 months ]
    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 :
  1. AUC last [ Time Frame: 36 months ]
    The area under the concentration (AUC) -time curve calculated to the last quantifiable concentration point (mass* time/volume)

  2. AUC tau [ Time Frame: 36 months ]
    Area under the concentration-time curve calculated to the end of the dosing interval (tau) (mass* time/volume)

  3. AUC inf [ Time Frame: 36 months ]
    The area under the concentration-time curve extrapolated to infinity (mass*time/volume)

  4. Cmax [ Time Frame: 36 months ]
    The maximum observed concentration (Cmax) following dose administration (mass/volume)

  5. Tmax [ Time Frame: 36 months ]
    The time to reach the maximum observed concentration (time)

  6. Cmin [ Time Frame: 36 months ]
    Minimum observed plasma concentration (mass/volume)

  7. Lambda_z [ Time Frame: 36 months ]
    Terminal elimination rate constant (1/time)

  8. T1/2 [ Time Frame: 36 months ]
    Elimination half-life, determined as 0.693/Lambda_z (time)

  9. CL/F [ Time Frame: 36 months ]
    Apparent systemic clearance of drug from the plasma (volume x time -1)

  10. Vz/F [ Time Frame: 36 months ]
    Apparent volume of distribution during the terminal elimination phase (volume)

  11. Best overall response (BOR) [ Time Frame: 36 months ]
    Best overall response will be summarized with accompanying 90% exact binomial confidence interval.

  12. Overall response rate (ORR) [ Time Frame: 36 months ]
    Overall response rate will be summarized with accompanying 90% exact binomial confidence interval.

  13. Progression free survival (PFS) [ Time Frame: 36 months ]
    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.

  14. Disease control rate (DCR) [ Time Frame: 36 months ]
    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

  15. Time to response (TTR) [ Time Frame: 36 months ]
    Kaplan-Meier estimates may be provided if sufficient numbers of patients respond.

  16. Tumor infiltrating lymphocytes (TIL) [ Time Frame: 36 months ]
    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.

  17. Cytokines [ Time Frame: 36 months ]
    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.


Other Outcome Measures:
  1. Change in mutation burden in tumor and in circulation [ Time Frame: 36 months ]
    Changes from baseline in DNA tumor sample in injected and distal lesions and in cell free (cf) DNA at end of study treatment.



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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:

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


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): NCT03172936


Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
United States, California
Novartis Investigative Site Recruiting
Los Angeles, California, United States, 90025
United States, Illinois
Novartis Investigative Site Recruiting
Chicago, Illinois, United States, 60637
Contact: Matthew Weist    773-702-1835    mweist@medicine.bsd.uchicago.edu   
Principal Investigator: Jason Luke         
United States, Texas
Novartis Investigative Site Recruiting
Houston, Texas, United States, 77030
Contact: Nilza Biaggi Labiosa    +1 713 745 4453    NMBiaggi@mdanderson.org   
Principal Investigator: Funda Meric-Bernstam         
Australia, Victoria
Novartis Investigative Site Recruiting
Melbourne, Victoria, Australia, 3000
Canada, Ontario
Novartis Investigative Site Recruiting
Toronto, Ontario, Canada, M5G 2M9
Germany
Novartis Investigative Site Recruiting
Essen, Germany, 45147
Japan
Novartis Investigative Site Recruiting
Chuo-ku, Tokyo, Japan, 104-0045
Netherlands
Novartis Investigative Site Recruiting
Amsterdam, Netherlands, 1066 CX
Switzerland
Novartis Investigative Site Recruiting
Zuerich, Switzerland, 8091
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Nancy Lewis, MD Novartis

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03172936     History of Changes
Other Study ID Numbers: CMIW815X2102J
2017-000707-25 ( EudraCT Number )
First Posted: June 1, 2017    Key Record Dates
Last Update Posted: August 24, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
injected lesion
distal lesion
abscopal activity
intratumoral
checkpoint inhibitor
cyclic dinucleotide
programmed cell death

Additional relevant MeSH terms:
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases