PDR001 Plus LAG525 for Patients With Advanced Solid and Hematologic Malignancies

NCT ID: NCT03365791

Last Updated: 2022-05-27

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

76 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-01-24

Study Completion Date

2020-09-17

Brief Summary

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The purpose of this signal seeking study is to determine whether treatment with PDR001 and LAG525 demonstrates sufficient efficacy in advanced malignancies to warrant further study.

Detailed Description

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This was a phase II, open-label study to determine the efficacy and safety of treatment with the combination of PDR001+LAG525 across multiple tumor types that are relapsed and/or refractory to available standard of care therapies. There were 7 tumor cohorts assessed: 1) Small cell lung cancer, 2) Gastric/esophageal adenocarcinoma, 3) Castration resistant prostate adenocarcinoma (CRPC), 4) Soft tissue sarcoma, 5) Ovarian adenocarcinoma, 6) Advanced well-differentiated neuroendocrine tumors and 7) Diffuse large B cell lymphoma (DLBCL).

Participants were treated with the combination of PDR001 300 mg with LAG525 400 mg once every 3 weeks (Q3W) via intravenous (i.v.) infusion. Participants received study treatment for a maximum of 2 years, or until disease progression (assessed by investigator per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) or the Revised Response Criteria for Malignant Lymphoma criteria (Cheson et al 2007)), unacceptable toxicity, death or discontinuation from study treatment for any other reason.

Conditions

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Small Cell Lung Cancer Gastric Adenocarcinoma Esophageal Adenocarcinoma Castration Resistant Prostate Adenocarcinoma Soft Tissue Sarcoma Ovarian Adenocarcinoma Advanced Well-differentiated Neuroendocrine Tumors Diffuse Large B Cell Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

This is a phase II, open-label, study to determine the efficacy and safety of treatment with the combination of PDR001+LAG525 across multiple tumor types that are relapsed and/or refractory to available standard of care therapies. Patients will receive study treatment for a maximum of 2 years. All disease assessments will be performed locally by the investigator.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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PDR001+LAG525

PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001.

Group Type EXPERIMENTAL

PDR001

Intervention Type BIOLOGICAL

PDR001 is a high-affinity, ligand-blocking, humanized anti-programmed death-1 (PD-1) IgG4 antibody that blocks the binding of Programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2) to PD-1.

LAG525

Intervention Type BIOLOGICAL

LAG525 is a high-affinity, ligand-blocking, humanized anti-LAG-3 IgG4 antibody which blocks the binding of the known LAG-3 ligand MHC class II to LAG-3.

Interventions

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PDR001

PDR001 is a high-affinity, ligand-blocking, humanized anti-programmed death-1 (PD-1) IgG4 antibody that blocks the binding of Programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2) to PD-1.

Intervention Type BIOLOGICAL

LAG525

LAG525 is a high-affinity, ligand-blocking, humanized anti-LAG-3 IgG4 antibody which blocks the binding of the known LAG-3 ligand MHC class II to LAG-3.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

Patients eligible for inclusion in this study had to meet all of the following criteria:

* Patient must have had at least one prior line of therapy for their disease and must not be beyond 4th progression/relapse of disease (5 maximum prior lines).
* Patient has a pathology confirmed diagnosis of a solid tumor or lymphoma listed in the section "condition". Patients must have measurable disease as per appropriate guidelines (Solid Tumors by RECIST 1.1 and Diffuse Large B-cell Lymphoma by Revised Response Criteria for Malignant Lymphoma - Cheson et al 2007).

Exclusion Criteria

Patients eligible for this study must not meet any of the following criteria:

* History of severe hypersensitivity reactions to other monoclonal antibodies.
* Impaired cardiac function or clinically significant cardiac disease.
* Active, known or suspected autoimmune disease or a documented history of autoimmune disease within three years prior to screening with a few exceptions as per protocol.
* Patients previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash or with replacement therapy for endocrinopathies should not be excluded.
* Patient with second primary malignancy within \< 3 years of first dose of study treatment.
* Prior immunotherapy treatment with PD-1, PD-L1, CTLA-4, or LAG-3 antibodies.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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California Pacific Medical Center Drug Shipment (2)

San Francisco, California, United States

Site Status

Hematology Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida, United States

Site Status

University Cancer and Blood Center, LLC

Athens, Georgia, United States

Site Status

Northwestern University Medical School

Chicago, Illinois, United States

Site Status

University of Illinois Cancer Center at Chicago SC

Chicago, Illinois, United States

Site Status

Illinois Cancer Care P.C. Jesse Brown VA

Peoria, Illinois, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

University of Iowa Hospitals and Clinics Comprehensive Cancer Center

Iowa City, Iowa, United States

Site Status

The University of Kansas Clinical Research Center

Fairway, Kansas, United States

Site Status

Weinberg Cancer Institute at Franklin Square Hospital

Baltimore, Maryland, United States

Site Status

Billings Clinic Dept of Billings Clinic(2)

Billings, Montana, United States

Site Status

Oncology Hematology West Nebraska Cancer Specialists

Omaha, Nebraska, United States

Site Status

Comprehensive Cancer Centers

Las Vegas, Nevada, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Oncology Consultants Oncology Consultants

Houston, Texas, United States

Site Status

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Kadlec Clinic Hematology and Oncology

Kennewick, Washington, United States

Site Status

Providence Regional Cancer System SC

Lacey, Washington, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=974

A Plain Language Trial Summary is available on novctrd.com

Other Identifiers

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CPDR001XUS01

Identifier Type: -

Identifier Source: org_study_id

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