Sym022 (Anti-LAG-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas

NCT ID: NCT03489369

Last Updated: 2021-02-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-08
• Study Completion Date: 2020-01-06

Brief Summary

This is the first study to test Sym022 in humans. The primary purpose of this study is to see if Sym022 is safe and tolerable for patients with locally advanced/unresectable or metastatic solid tumor malignancies or lymphomas that are refractory to available therapy or for which no standard therapy is available.

Detailed Description

This study will evaluate the preliminary safety, tolerability, and dose-limiting toxicities (DLTs) of Sym022, an anti-lymphocyte activation gene 3 (anti-LAG-3) monoclonal antibody (mAb). The goal is to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of sequential escalating doses of Sym022 when administered once every 2 weeks (Q2W) by intravenous (IV) infusion to patient cohorts with locally advanced/ unresectable or metastatic solid tumor malignancies or lymphomas that are refractory to available therapy or for which no standard therapy is available. If an MTD is not identified, a maximum administered dose (MAD) will be determined. Sym022 will be given to patients in escalating dose cohorts; each patient will be given one fixed dose level.

Conditions

Metastatic Cancer; Solid Tumor; Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sym022

Sym022 will be administered at up to 4 planned dose levels.

Group Type: EXPERIMENTAL

Sym022

Intervention Type: DRUG

Sym022 is a recombinant, fully human antibody that binds LAG-3 and blocks the LAG-3/major histocompatibility complex class II (MHC-II) interaction, thus allowing for increased T-cell proliferation and cytokine production.

Interventions

Sym022

Sym022 is a recombinant, fully human antibody that binds LAG-3 and blocks the LAG-3/major histocompatibility complex class II (MHC-II) interaction, thus allowing for increased T-cell proliferation and cytokine production.

Intervention Type: DRUG

Other Intervention Names

Anti-LAG-3

Eligibility Criteria

Inclusion Criteria

• Male or female patients, ≥ 18 years of age at the time of obtaining informed consent.
• Documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic; patients with documented lymphomas.
• Malignancy (solid tumor or lymphoma) that is currently not amenable to surgical intervention due to either medical contraindications or nonresectability of the tumor.
• Refractory to or intolerant of existing therapy(ies) known to provide clinical benefit.
• Measurable or non-measurable disease according to RECIST v1.1 or RECIL 2017.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Not of childbearing potential or who agree to use a highly effective method of contraception during the study beginning within 2 weeks prior to the first dose and continuing until 6 months after the last dose of study drug.

Exclusion Criteria

• Women who are pregnant or lactating, or intending to become pregnant before, during, or within 6 months after the last dose of study drug. Women of childbearing potential (WOCBP) and fertile men with WOCBP partner(s), not using and not willing to use a highly effective method of contraception.
• Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression, patients with any of the above not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
• Hematologic malignancies other than lymphomas.
• Active thrombosis, or a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) within 4 weeks prior to Cycle 1/Day 1 (C1/D1) unless adequately treated and considered stable
• Active uncontrolled bleeding or a known bleeding diathesis
• Clinically significant cardiovascular disease or condition
• Significant pulmonary disease or condition
• Current or recent (within 6 months) significant gastrointestinal (GI) disease or condition.
• An active, known, or suspected autoimmune disease, or a documented history of autoimmune disease or syndrome, requiring systemic steroids or other immunosuppressive medications.
• History of organ transplantation (e.g. stem cell or solid organ transplant)
• History of significant toxicities associated with previous administration of immune checkpoint inhibitors that necessitated permanent discontinuation of that therapy
• Patients with unresolved > Grade 1 toxicity associated with any prior antineoplastic therapy, with exceptions.
• Inadequate recovery from any prior surgical procedure, or having undergone any major surgical procedure within 4 weeks prior to C1/D1.
• Known history of human immunodeficiency virus (HIV) or known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
• Other Inhibitors of LAG-3
• Any antineoplastic agent for the primary malignancy (standard or investigational) without delayed toxicity within 4 weeks or 5 plasma half-lives, whichever is shortest, prior to first administration of study drug and during study
• Any other investigational treatments within 4 weeks prior to and during study
• Radiotherapy for target lesions within 4 weeks prior to first administration of study drug unless PD has been documented in the lesion following treatment, and during study.
• Radiotherapy for non-target lesions within 1 week prior to first administration of study drug
• Immunosuppressive or systemic hormonal therapy
• Prophylactic use of hematopoietic growth factors within 1 week prior to first administration of study drug and during Cycle 1 of study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Symphogen A/S

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lillian Siu, MD, FRCPC

Role: PRINCIPAL_INVESTIGATOR

Princess Margaret Cancer Centre

Locations

South Texas Accelerated Research Therapeutics (START) Midwest

Grand Rapids, Michigan, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Countries

United States; Canada

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Sym022-01

Identifier Type: -

Identifier Source: org_study_id