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

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

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

Study Overview

• Status: Terminated
• Conditions: Solid Tumors and Lymphomas
• Intervention / Treatment: Drug: MIW815; Biological: PDR001

Detailed Description

This was 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 were explored in two dose escalation groups in accessible cutaneous or subcutaneous lesions. The optional dose confirmation group exploring intratumoral injection of viscerally located lesions was not opened due to the program's early termination.

Group A included patients with accessible solid tumors and lymphomas. This group received 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 included patients with accessible solid tumors and lymphomas. This group received a fixed dose of PDR001 i.v. on day 1 of every 28 day cycle and an intratumoral injection of MIW815 (ADU-S100) on day 1 of every 28 day cycle.

Once the dose and dose schedule had been confirmed, the plan was to open the dose expansion part of the study. However, the expansion phase of the study was not opened to enrollment due to the program's early termination.

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • North Sydney, New South Wales, Australia, 2060
      • Novartis Investigative Site
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Novartis Investigative Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Novartis Investigative Site
• Germany
  • Essen, Germany, 45147
    • Novartis Investigative Site
• Japan
  • Tokyo
    • Chuo ku, Tokyo, Japan, 104 0045
      • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Novartis Investigative Site
• Spain
  • Catalunya
    • Hospitalet de LLobregat, Catalunya, Spain, 08907
      • Novartis Investigative Site
• Switzerland
  • Zurich, Switzerland, 8091
    • Novartis Investigative Site
• United States
  • California
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Novartis Investigative Site
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dosing Schedule A; Patients were treated with MIW815 (ADU-S100) via intratumoral injection for 3 weeks 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 were 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC inf	The area under the concentration-time curve extrapolated to infinity (mass*time/volume)	36 months
AUC last	The area under the concentration (AUC) -time curve calculated to the last quantifiable concentration point (mass* time/volume)	36 months
AUC tau	Area under the concentration-time curve calculated to the end of the dosing interval (tau) (mass* time/volume)	36 months
Tmax	The time to reach the maximum observed concentration (time)	36 months
Cmax	The maximum observed concentration (Cmax) following dose administration (mass/volume)	36 months
Lambda_z	Terminal elimination rate constant (1/time)	36 months
CL/F	Apparent systemic clearance of drug from the plasma (volume x time -1)	36 months
T1/2	Elimination half-life, determined as 0.693/Lambda_z (time)	36 months
Vz/F	Apparent volume of distribution during the terminal elimination phase (volume)	36 months
Best overall response (BOR)	Best overall response will be summarized	36 months
Overall response rate (ORR)	Overall response rate will be summarized with accompanying 90% exact binomial confidence interval (CI).	36 months
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.	36 months
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	36 months
Time to response (TTR)	Time To Response is the time from first dose to first documented response (CR or PR). TTR will be summarized	36 months
Duration of Response (DOR)	Duration of response is defined as the time from the date of the first documented response (CR or PR), to the date of first documented progression, or death due to study indication. Estimates will use Kaplan-Meier method	36 months
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.	36 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Nancy Lewis, MD, Novartis

Publications and helpful links

General Publications

• Gogoi H, Mansouri S, Jin L. The Age of Cyclic Dinucleotide Vaccine Adjuvants. Vaccines (Basel). 2020 Aug 13;8(3):453. doi: 10.3390/vaccines8030453.

Helpful Links

• Study Results
• A Plain Language Trial Summary is available on novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2017
• Primary Completion (Actual): December 18, 2020
• Study Completion (Actual): December 18, 2020

Study Registration Dates

• First Submitted: May 30, 2017
• First Submitted That Met QC Criteria: May 31, 2017
• First Posted (Actual): June 1, 2017

Study Record Updates

• Last Update Posted (Actual): May 3, 2022
• Last Update Submitted That Met QC Criteria: April 27, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: checkpoint inhibitor; programmed cell death; intratumoral; injected lesion; distal lesion; abscopal activity; cyclic dinucleotide
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immune Checkpoint Inhibitors; Spartalizumab
• Other Study ID Numbers: CMIW815X2102J; 2017-000707-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No