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

Phase 1TerminatedNCT03172936

Novartis Pharmaceuticals106 enrolled

Overview

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

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

106

Conditions

Solid Tumors and Lymphomas

Interventions

MIW815DRUG

MIW 815 (ADU-S100) is a STING agonist

PDR001BIOLOGICAL

PDR001 is an anti-PD-1 antibody

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (12)

The Angeles Clinic and Research Institute

Los Angeles, California, United States

Novartis Investigative Site

Chicago, Illinois, United States

MD Anderson Cancer Center

Houston, Texas, United States

Outcomes

Primary Outcomes

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

Time frame: 24 months

Secondary Outcomes

AUC inf

The area under the concentration-time curve extrapolated to infinity (mass\*time/volume)

Time frame: 36 months

AUC last

The area under the concentration (AUC) -time curve calculated to the last quantifiable concentration point (mass\* time/volume)

Time frame: 36 months

AUC tau

Area under the concentration-time curve calculated to the end of the dosing interval (tau) (mass\* time/volume)

Time frame: 36 months

Tmax

The time to reach the maximum observed concentration (time)

Time frame: 36 months

Cmax

The maximum observed concentration (Cmax) following dose administration (mass/volume)

Time frame: 36 months

Lambda_z

Terminal elimination rate constant (1/time)

Time frame: 36 months

CL/F

Apparent systemic clearance of drug from the plasma (volume x time -1)

Data from ClinicalTrials.gov

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