Clinical trial NCT03172936: Study of the Safety and Efficacy of MIW815 With PDR001 in Patients With Advanced/Metastatic Solid Tumors or Lymphomas
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumors and Lymphomas
Keywords: injected lesion
distal lesion
abscopal activity
intratumoral
checkpoint inhibitor
cyclic dinucleotide
programmed cell death
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-06-01
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study was comprised of two treatment arms.

Group A included patients with accessible solid tumors and lymphomas. This group received 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 included patients with accessible solid tumors and lymphomas. This group received a fixed dose of PDR001 intravenous 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 maximum tolerated dose and/or recommended dose for expansion had been determined, the plan was to open the expansion part of the study. However, the dose expansion phase of the study was not opened to enrollment due to the program's early termination.
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Incidence of dose limiting toxicities (DLTs)
timeFrame: 24 months
Secondary outcomes:
measure: AUC inf
timeFrame: 36 months
measure: AUC last
timeFrame: 36 months
measure: AUC tau
timeFrame: 36 months
measure: Tmax
timeFrame: 36 months
measure: Cmax
timeFrame: 36 months
measure: Lambda_z
timeFrame: 36 months
measure: CL/F
timeFrame: 36 months
measure: T1/2
timeFrame: 36 months
measure: Vz/F
timeFrame: 36 months
measure: Best overall response (BOR)
timeFrame: 36 months
measure: Overall response rate (ORR)
timeFrame: 36 months
measure: Progression free survival (PFS)
timeFrame: 36 months
measure: Disease control rate (DCR)
timeFrame: 36 months
measure: Time to response (TTR)
timeFrame: 36 months
measure: Duration of Response (DOR)
timeFrame: 36 months
measure: Tumor infiltrating lymphocytes (TIL)
timeFrame: 36 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: North Sydney
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Zurich
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis
name: Nancy Lewis, MD
role: STUDY_DIRECTOR
References:
citation: 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.