Sym023 (Anti-TIM-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas

NCT03489343 | Completed Phase 1 Results FDA Drug

• 1 other identifier: Sym023-01
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 4

Brief Summary

This was the first study to test Sym023 in humans. The primary purpose of this study was to see if Sym023 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.

Conditions

Metastatic Cancer; Solid Tumor; Lymphoma

Keywords

Locally advanced/unresectable; Metastatic solid tumor; Lymphoma; Anti-TIM-3; TIM-3; TIM3

Outcome Measures

Primary Outcomes (1)

• Assessment of Treatment Emergent Adverse Events (AEs) Meeting Dose-limiting Toxicity (DLT) Criteria.

  Assess the safety and tolerability of Sym023 on a Q2W (once every 2 weeks) schedule to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). Assessment based on the occurrence of AEs meeting DLT criteria measured during Cycle 1. The MTD was to be determined by those DLTs that occurred during C1 in either more than 1 patient in a 3 to 6 patient cohort or ≥33.3% of patients in the event of an expanded 7 to 12 patient cohort. One patient in the 10.0 mg/kg dose cohort was not evaluable for MTD as she did not complete C1 for a reason other than drug toxicity (i.e., discontinuation after 1 dose due to patient withdrawal of consent). However, this patient was included in the evaluation of other outcomes.

  28 days

Secondary Outcomes (11)

• Evaluation of the Immunogenicity of Sym023.

  Baseline up to 6-months follow-up, approximately 1 year

• Evaluation of Objective Response (OR) or Stable Disease (SD) by RECIST v1.1

  24 months

• Evaluation of Objective Response (OR) or Stable Disease (SD) by iRECIST

  24 months

• Evaluation of Objective Response (OR) or Stable Disease (SD) by RECIL 2017.

  24 months

• Time to Progression (TTP) of Disease.

  24 months

Study Arms (7)

Sym023 0.03 mg/kg

EXPERIMENTAL

Sym023 was administered at a dose of 0.03 mg/kg by intravenous infusion

Drug: Sym023

Sym023 0.1 mg/kg

EXPERIMENTAL

Sym023 was administered at a dose of 0.1 mg/kg by intravenous infusion

Drug: Sym023

Sym023 0.3 mg/kg

EXPERIMENTAL

Sym023 was administered at a dose of 0.3 mg/kg by intravenous infusion

Drug: Sym023

Sym023 1.0 mg/kg

EXPERIMENTAL

Sym023 was administered at a dose of 1.0 mg/kg by intravenous infusion

Drug: Sym023

Sym023 3.0 mg/kg

EXPERIMENTAL

Sym023 was administered at a dose of 3.0 mg/kg by intravenous infusion

Drug: Sym023

Sym023 10.0 mg/kg

EXPERIMENTAL

Sym023 was administered at a dose of 10.0 mg/kg by intravenous infusion

Drug: Sym023

Sym023 20.0 mg/kg

EXPERIMENTAL

Sym023 was administered at a dose of 20.0 mg/kg by intravenous infusion

Drug: Sym023

Interventions

Sym023 DRUG

Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.

Also known as: Anti-TIM-3

Sym023 0.03 mg/kg; Sym023 0.1 mg/kg; Sym023 0.3 mg/kg; Sym023 1.0 mg/kg; Sym023 10.0 mg/kg; Sym023 20.0 mg/kg; Sym023 3.0 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 ocular disease or condition, including history of autoimmune or inflammatory disorder.
• 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 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).

Sponsors & Collaborators

• Symphogen A/S: lead

Study Sites (4)

South Texas Accelerated Research Therapeutics (START) Midwest

Grand Rapids, Michigan, 49503, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78240, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Lymphoma

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Medical Director
• Organization: Symphogen AS

info@symphogen.com

0045 45265050

Study Officials

• Lillian Siu, MD, FRCPC

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2018
• First Posted: April 5, 2018
• Study Start: May 24, 2018
• Primary Completion: June 3, 2020
• Study Completion: June 3, 2020
• Last Updated: October 12, 2021
• Results First Posted: October 12, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (3)