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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03172936




Registration number
NCT03172936
Ethics application status
Date submitted
30/05/2017
Date registered
1/06/2017
Date last updated
22/01/2020

Titles & IDs
Public title
Study of the Safety and Efficacy of MIW815 With PDR001 to Patients With Advanced/Metastatic Solid Tumors or Lymphomas
Scientific 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
Secondary ID [1] 0 0
2017-000707-25
Secondary ID [2] 0 0
CMIW815X2102J
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumors and Lymphomas 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MIW815
Other interventions - PDR001

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

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


Treatment: Drugs: MIW815
MIW 815 (ADU-S100) is a STING agonist

Other interventions: PDR001
PDR001 is an anti-PD-1 antibody

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of dose limiting toxicities (DLTs) - 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
Timepoint [1] 0 0
24 months
Secondary outcome [1] 0 0
AUC last - The area under the concentration (AUC) -time curve calculated to the last quantifiable concentration point (mass* time/volume)
Timepoint [1] 0 0
36 months
Secondary outcome [2] 0 0
AUC tau - Area under the concentration-time curve calculated to the end of the dosing interval (tau) (mass* time/volume)
Timepoint [2] 0 0
36 months
Secondary outcome [3] 0 0
AUC inf - The area under the concentration-time curve extrapolated to infinity (mass*time/volume)
Timepoint [3] 0 0
36 months
Secondary outcome [4] 0 0
Cmax - The maximum observed concentration (Cmax) following dose administration (mass/volume)
Timepoint [4] 0 0
36 months
Secondary outcome [5] 0 0
Tmax - The time to reach the maximum observed concentration (time)
Timepoint [5] 0 0
36 months
Secondary outcome [6] 0 0
Cmin - Minimum observed plasma concentration (mass/volume)
Timepoint [6] 0 0
36 months
Secondary outcome [7] 0 0
Lambda_z - Terminal elimination rate constant (1/time)
Timepoint [7] 0 0
36 months
Secondary outcome [8] 0 0
T1/2 - Elimination half-life, determined as 0.693/Lambda_z (time)
Timepoint [8] 0 0
36 months
Secondary outcome [9] 0 0
CL/F - Apparent systemic clearance of drug from the plasma (volume x time -1)
Timepoint [9] 0 0
36 months
Secondary outcome [10] 0 0
Vz/F - Apparent volume of distribution during the terminal elimination phase (volume)
Timepoint [10] 0 0
36 months
Secondary outcome [11] 0 0
Best overall response (BOR) - Best overall response will be summarized with accompanying 90% exact binomial confidence interval.
Timepoint [11] 0 0
36 months
Secondary outcome [12] 0 0
Overall response rate (ORR) - Overall response rate will be summarized with accompanying 90% exact binomial confidence interval.
Timepoint [12] 0 0
36 months
Secondary outcome [13] 0 0
Progression free survival (PFS) - 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.
Timepoint [13] 0 0
36 months
Secondary outcome [14] 0 0
Disease control rate (DCR) - 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
Timepoint [14] 0 0
36 months
Secondary outcome [15] 0 0
Time to response (TTR) - Kaplan-Meier estimates may be provided if sufficient numbers of patients respond.
Timepoint [15] 0 0
36 months
Secondary outcome [16] 0 0
Tumor infiltrating lymphocytes (TIL) - 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.
Timepoint [16] 0 0
36 months
Secondary outcome [17] 0 0
Cytokines - 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.
Timepoint [17] 0 0
36 months

Eligibility
Key inclusion criteria
ECOG = 1 Willing to undergo tumor biopsies from injected and distal lesions

Must have two biopsy accessible lesions:
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - North Sydney
Recruitment hospital [2] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
2060 - North Sydney
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
United States of America
State/province [4] 0 0
Washington
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario
Country [6] 0 0
Germany
State/province [6] 0 0
Essen
Country [7] 0 0
Japan
State/province [7] 0 0
Tokyo
Country [8] 0 0
Netherlands
State/province [8] 0 0
Amsterdam
Country [9] 0 0
Spain
State/province [9] 0 0
Catalunya
Country [10] 0 0
Switzerland
State/province [10] 0 0
Zuerich

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03172936
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Nancy Lewis, MD
Address 0 0
Novartis
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications