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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03172936
Recruitment Status : Active, not recruiting
First Posted : June 1, 2017
Last Update Posted : November 6, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 106 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 Ib, Open Label, Multicenter Study of the Safety and Efficacy of MIW815 (ADU-S100) Administered by Intratumoral Injection With PDR001 to Patients With Advanced/Metastatic Solid Tumors or Lymphomas
Actual Study Start Date : September 8, 2017
Estimated Primary Completion Date : December 18, 2020
Estimated Study Completion Date : December 18, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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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


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

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

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

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

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

  7. 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.

  8. 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

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

  10. Duration of Response (DOR [ Time Frame: 36 months ]
    The duration of response is calculated from the assessment date of the first overall lesion response of CR/PR until one of the following: Date of Death, Date of Progression, Date of last adequate tumor assessment or Date of next scheduled assessment

  11. 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.

  12. 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.


Eligibility Criteria
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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

Contacts and Locations
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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


Locations
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United States, California
The Angeles Clinic and Research Institute
Los Angeles, California, United States, 90025
United States, Illinois
Novartis Investigative Site
Chicago, Illinois, United States, 60637
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98105
Australia, New South Wales
Novartis Investigative Site
North Sydney, New South Wales, Australia, 2060
Australia, Victoria
Novartis Investigative Site
Melbourne, Victoria, Australia, 3000
Canada, Ontario
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 2M9
Germany
Novartis Investigative Site
Essen, Germany, 45147
Japan
Novartis Investigative Site
Chuo ku, Tokyo, Japan, 104 0045
Netherlands
Novartis Investigative Site
Amsterdam, Netherlands, 1066 CX
Spain
Novartis Investigative Site
Hospitalet de LLobregat, Catalunya, Spain, 08907
Switzerland
Novartis Investigative Site
Zuerich, Switzerland, 8091
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Nancy Lewis, MD Novartis
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03172936    
Other Study ID Numbers: CMIW815X2102J
2017-000707-25 ( EudraCT Number )
First Posted: June 1, 2017    Key Record Dates
Last Update Posted: November 6, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
 Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases