Phase I Study of PDR001 in Patients With Advanced Malignancies.

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT02678260

Collaborator

(none)

Enrollment

Locations

Arm

18.4

Actual Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to characterize the safety, tolerability, Pharmacokinetics (PK), and antitumor activity of PDR001 administered intravenous (i.v.) as a single agent to Japanese patients.

Condition or Disease	Intervention/Treatment	Phase
Advanced Malignancies	Drug: PDR001	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase-I Study of PDR001 Administered to Japanese Patients With Advanced Malignancies

Actual Study Start Date :

Feb 19, 2016

Actual Primary Completion Date :

Sep 1, 2017

Actual Study Completion Date :

Sep 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PDR001 PDR001 will be administered i.v. every two weeks until a patient experiences unacceptable toxicity, progressive disease as per irRC and/or treatment is discontinued at the discretion of the investigator or the patient. The treatment period will begin on Cycle 1 Day 1. For the purpose of scheduling and evaluations, a treatment cycle will consist of 28 days. During the study, cohorts of patients will be treated with PDR001 until the maximum tolerated dose (MTD) is reached or a lower recommended dose (RD) is established.	Drug: PDR001 PDR001 is a high-affinity, ligand-blocking, humanized anti-PD-1 IgG4 antibody that blocks the binding of PD-L1 and PD-L2 to PD-1.

Arm

Intervention/Treatment

Experimental: PDR001

PDR001 will be administered i.v. every two weeks until a patient experiences unacceptable toxicity, progressive disease as per irRC and/or treatment is discontinued at the discretion of the investigator or the patient. The treatment period will begin on Cycle 1 Day 1. For the purpose of scheduling and evaluations, a treatment cycle will consist of 28 days. During the study, cohorts of patients will be treated with PDR001 until the maximum tolerated dose (MTD) is reached or a lower recommended dose (RD) is established.

Drug: PDR001

PDR001 is a high-affinity, ligand-blocking, humanized anti-PD-1 IgG4 antibody that blocks the binding of PD-L1 and PD-L2 to PD-1.

Outcome Measures

Primary Outcome Measures

Incidence of dose limiting toxicities (DLTs) [28 days]
cycle = 28 days

Secondary Outcome Measures

PK parameter: AUC [Cycle 1 Day 1 (C1D1), Cycle 3 Day 1 (C3D1)]
To characterize the PK profile of PDR001; cycle = 28 days
Serum concentration vs. time profiles [C1D1, C3D1]
Serum concentration of PDR001 at the scheduled timepoints up to 336 hours after administration
Presence and/or concentration of anti-PDR001 antibodies [Day 1 on from C1 to C6]
To assess the emergence of anti-PDR001 antibodies following one or more intravenous infusions of PDR001.
Objective response rate (ORR) [up to cycle 11; every 2 cycles (8 weeks), after cycle 12; every 3 cycles (12 weeks)]
cycle = 28 days
Duration of response rate (DOR) [up to cycle 11; every 2 cycles (8 weeks), after cycle 12; every 3 cycles (12 weeks)]
cycle = 28 days
Disease control rate (DCR) [up to cycle 11; every 2 cycles (8 weeks), after cycle 12; every 3 cycles (12 weeks)]
cycle = 28 days
PK parameter: Cmax [Cycle 1 Day 1 (C1D1), Cycle 3 Day 1 (C3D1)]
To characterize the PK profile of PDR001; cycle = 28 days
PK parameter: Tmax [Cycle 1 Day 1 (C1D1), Cycle 3 Day 1 (C3D1)]
To characterize the PK profile of PDR001; cycle = 28 days
PK parameter: half-life [Cycle 1 Day 1 (C1D1), Cycle 3 Day 1 (C3D1)]
To characterize the PK profile of PDR001; cycle = 28 days

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by response evaluation criteria in solid tumors (RECIST) version 1.1, who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists
ECOG Performance Status ≤ 2

Exclusion Criteria:

Active autoimmune disease
Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
Prior PD-1- or PD-L1-directed therapy

Other protocol defined inclusion/exclusion may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Nagoya	Aichi	Japan	466-8560
2	Novartis Investigative Site	Kashiwa	Chiba	Japan	277-8577
3	Novartis Investigative Site	Kobe-city	Hyogo	Japan	650-0017