Phase I Study of PDR001 in Patients With Advanced Malignancies.

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Malignancies
• Intervention / Treatment: Drug: PDR001

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Nagoya, Aichi, Japan, 466-8560
      • Novartis Investigative Site
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • Novartis Investigative Site
  • Hyogo
    • Kobe-city, Hyogo, Japan, 650-0017
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose limiting toxicities (DLTs)	cycle = 28 days	28 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2016
• Primary Completion (Actual): September 1, 2017
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: January 21, 2016
• First Submitted That Met QC Criteria: February 4, 2016
• First Posted (Estimate): February 9, 2016

Study Record Updates

• Last Update Posted (Actual): June 8, 2018
• Last Update Submitted That Met QC Criteria: June 6, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: PDR001; Japanese patients; adults; Advanced malignancies
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immune Checkpoint Inhibitors; Spartalizumab
• Other Study ID Numbers: CPDR001X1101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No