Description:
The purpose of this study was to characterize the safety, tolerability, pharmacokinetics,
pharmacodynamics and antitumor activity of MIW815 (ADU-S100) in combination with PDR001.
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
CMIW815X2102J
- SECONDARY ID:
2017-000707-25
- NCT ID:
NCT03172936
Conditions
- Solid Tumors and Lymphomas
Interventions
| Drug | Synonyms | Arms |
|---|
| MIW815 | | Dosing Schedule A |
| PDR001 | | Dosing Schedule A |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Dosing Schedule A | Experimental | 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 | |
| Dosing Schedule B | Experimental | 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 | |
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Incidence of dose limiting toxicities (DLTs) |
| Time Frame: | 24 months |
| Safety Issue: | |
| Description: | 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
| Measure: | AUC inf |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | The area under the concentration-time curve extrapolated to infinity (mass*time/volume) |
| Measure: | AUC last |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | The area under the concentration (AUC) -time curve calculated to the last quantifiable concentration point (mass* time/volume) |
| Measure: | AUC tau |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | Area under the concentration-time curve calculated to the end of the dosing interval (tau) (mass* time/volume) |
| Measure: | Tmax |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | The time to reach the maximum observed concentration (time) |
| Measure: | Cmax |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | The maximum observed concentration (Cmax) following dose administration (mass/volume) |
| Measure: | Lambda_z |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | Terminal elimination rate constant (1/time) |
| Measure: | CL/F |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | Apparent systemic clearance of drug from the plasma (volume x time -1) |
| Measure: | T1/2 |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | Elimination half-life, determined as 0.693/Lambda_z (time) |
| Measure: | Vz/F |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | Apparent volume of distribution during the terminal elimination phase (volume) |
| Measure: | Best overall response (BOR) |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | Best overall response will be summarized |
| Measure: | Overall response rate (ORR) |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | Overall response rate will be summarized with accompanying 90% exact binomial confidence interval (CI). |
| Measure: | Progression free survival (PFS) |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Disease control rate (DCR) |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Time to response (TTR) |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | Time To Response is the time from first dose to first documented response (CR or PR). TTR will be summarized |
| Measure: | Duration of Response (DOR) |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Tumor infiltrating lymphocytes (TIL) |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | 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. |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- injected lesion
- distal lesion
- abscopal activity
- intratumoral
- checkpoint inhibitor
- cyclic dinucleotide
- programmed cell death
Last Updated
February 24, 2021
