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

Solid Tumors and Lymphomas Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT03172936
• Other study ID #: CMIW815X2102J
• Secondary ID: 2017-000707-25
• Status: Terminated
• Phase: Phase 1
• Start date: September 8, 2017
• Est. completion date: December 18, 2020

Study information

• Verified date: April 2022
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 106
• Est. completion date: December 18, 2020
• Est. primary completion date: December 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Solid Tumors and Lymphomas

Intervention

Drug:
• MIW815
MIW 815 (ADU-S100) is a STING agonist

Biological:
• PDR001
PDR001 is an anti-PD-1 antibody

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Melbourne	Victoria
Australia	Novartis Investigative Site	North Sydney	New South Wales
Canada	Novartis Investigative Site	Toronto	Ontario
Germany	Novartis Investigative Site	Essen
Japan	Novartis Investigative Site	Chuo ku	Tokyo
Netherlands	Novartis Investigative Site	Amsterdam
Spain	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya
Switzerland	Novartis Investigative Site	Zurich
United States	Novartis Investigative Site	Chicago	Illinois
United States	MD Anderson Cancer Center	Houston	Texas
United States	The Angeles Clinic and Research Institute	Los Angeles	California
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Germany,  Japan,  Netherlands,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	AUC inf	The area under the concentration-time curve extrapolated to infinity (mass*time/volume)	36 months
Secondary	AUC last	The area under the concentration (AUC) -time curve calculated to the last quantifiable concentration point (mass* time/volume)	36 months
Secondary	AUC tau	Area under the concentration-time curve calculated to the end of the dosing interval (tau) (mass* time/volume)	36 months
Secondary	Tmax	The time to reach the maximum observed concentration (time)	36 months
Secondary	Cmax	The maximum observed concentration (Cmax) following dose administration (mass/volume)	36 months
Secondary	Lambda_z	Terminal elimination rate constant (1/time)	36 months
Secondary	CL/F	Apparent systemic clearance of drug from the plasma (volume x time -1)	36 months
Secondary	T1/2	Elimination half-life, determined as 0.693/Lambda_z (time)	36 months
Secondary	Vz/F	Apparent volume of distribution during the terminal elimination phase (volume)	36 months
Secondary	Best overall response (BOR)	Best overall response will be summarized	36 months
Secondary	Overall response rate (ORR)	Overall response rate will be summarized with accompanying 90% exact binomial confidence interval (CI).	36 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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