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

Phase 1

Terminated

• Conditions: Solid Tumors and Lymphomas
• Interventions: Drug: MIW815; Biological: PDR001

• Registration Number: NCT03172936
• Lead Sponsor: Novartis Pharmaceuticals

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.

Study Timeline

• Study First Submitted: 2017-05-30
• Study First Submitted QC: 2017-05-31
• Study First Posted: 2017-06-01
• Study Start: 2017-09-08
• Primary Completion: 2020-12-18
• Study Completion: 2020-12-18
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-27
• Last Update Posted: 2022-05-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 106

Inclusion Criteria

ECOG ≤ 1 Willing to undergo tumor biopsies from injected and distal lesions

Must have two biopsy accessible lesions:

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dosing Schedule A	PDR001	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	PDR001	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
Dosing Schedule A	MIW815	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	MIW815	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

Primary Outcome Measures

Name	Time	Method
Incidence of dose limiting toxicities (DLTs)	24 months	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

Name	Time	Method
Duration of Response (DOR)	36 months	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
AUC inf	36 months	The area under the concentration-time curve extrapolated to infinity (mass\*time/volume)
AUC tau	36 months	Area under the concentration-time curve calculated to the end of the dosing interval (tau) (mass\* time/volume)
T1/2	36 months	Elimination half-life, determined as 0.693/Lambda_z (time)
Overall response rate (ORR)	36 months	Overall response rate will be summarized with accompanying 90% exact binomial confidence interval (CI).
Tumor infiltrating lymphocytes (TIL)	36 months	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.
Progression free survival (PFS)	36 months	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.
AUC last	36 months	The area under the concentration (AUC) -time curve calculated to the last quantifiable concentration point (mass\* time/volume)
Tmax	36 months	The time to reach the maximum observed concentration (time)
Lambda_z	36 months	Terminal elimination rate constant (1/time)
CL/F	36 months	Apparent systemic clearance of drug from the plasma (volume x time -1)
Vz/F	36 months	Apparent volume of distribution during the terminal elimination phase (volume)
Best overall response (BOR)	36 months	Best overall response will be summarized
Disease control rate (DCR)	36 months	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
Time to response (TTR)	36 months	Time To Response is the time from first dose to first documented response (CR or PR). TTR will be summarized
Cmax	36 months	The maximum observed concentration (Cmax) following dose administration (mass/volume)

Trial Locations

Locations (4)

Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Novartis Investigative Site; 🇨🇭 Zurich, Switzerland

The Angeles Clinic and Research Institute; 🇺🇸 Los Angeles, California, United States