Clinical trial NCT03489343: Sym023 (Anti-TIM-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas
Official title: A Phase 1, Open-Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Antineoplastic Activity of Sym023 (Anti-TIM-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Cancer
Solid Tumor
Lymphoma
Keywords: Locally advanced/unresectable
Metastatic solid tumor
Lymphoma
Anti-TIM-3
TIM-3
TIM3
Lead sponsor: Symphogen A/S
Sponsor class: INDUSTRY
First posted: 2018-04-05
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: This study evaluated the preliminary safety, tolerability, and dose-limiting toxicities (DLTs) of Sym023, a recombinant, fully human, anti-T-cell immunoglobulin and mucin-domain containing-3 (anti-TIM-3) monoclonal antibody (mAb). The goal was to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of sequential escalating doses of Sym023 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 was not identified, a maximum administered dose (MAD) was to be determined. Sym023 was given to patients in escalating dose cohorts; each patient was given one fixed dose level.

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 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).

Primary outcomes:
measure: Assessment of Treatment Emergent Adverse Events (AEs) Meeting Dose-limiting Toxicity (DLT) Criteria.
timeFrame: 28 days
Secondary outcomes:
measure: Evaluation of the Immunogenicity of Sym023.
timeFrame: Baseline up to 6-months follow-up, approximately 1 year
measure: Evaluation of Objective Response (OR) or Stable Disease (SD) by RECIST v1.1
timeFrame: 24 months
measure: Evaluation of Objective Response (OR) or Stable Disease (SD) by iRECIST
timeFrame: 24 months
measure: Evaluation of Objective Response (OR) or Stable Disease (SD) by RECIL 2017.
timeFrame: 24 months
measure: Time to Progression (TTP) of Disease.
timeFrame: 24 months
measure: Area Under the Concentration-time Curve in a Dosing Interval (AUC).
timeFrame: From before the start of the infusion to 168 hours after the end of the infusion
measure: Maximum Concentration (Cmax)
timeFrame: From before the start of the infusion to 168 hours after the end of the infusion
measure: Time to Reach Maximum Concentration (Tmax)
timeFrame: From before the start of the infusion to 168 hours after the end of the infusion
measure: Trough Concentration (Ctrough)
timeFrame: From before the start of the infusion to 168 hours after the end of the infusion
measure: Terminal Elimination Half-life (T½)
timeFrame: From before the start of the infusion to 168 hours after the end of the infusion
measure: Clearance (CL)
timeFrame: From before the start of the infusion to 168 hours after the end of the infusion
Other outcomes:
Locations:
city: Grand Rapids
country: United States
facility: South Texas Accelerated Research Therapeutics (START) Midwest
state: Michigan
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Lillian Siu, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: