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

Primary Purpose

Metastatic Cancer, Solid Tumor, Lymphoma

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Sym023

About this trial

This is an interventional treatment trial for Metastatic Cancer focused on measuring Locally advanced/unresectable, Metastatic solid tumor, Lymphoma, Anti-TIM-3, TIM-3, TIM3

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

South Texas Accelerated Research Therapeutics (START) Midwest
The University of Texas MD Anderson Cancer Center
NEXT Oncology
Princess Margaret Cancer Centre

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Arm Label

Sym023 0.03 mg/kg

Sym023 0.1 mg/kg

Sym023 0.3 mg/kg

Sym023 1.0 mg/kg

Sym023 3.0 mg/kg

Sym023 10.0 mg/kg

Sym023 20.0 mg/kg

Arm Description

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

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Evaluation of the Immunogenicity of Sym023.

Serum sampling to assess the potential for anti-drug antibody (ADA) formation. The number of patients with positive samples at indicated visits is presented.

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

OR or SD Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). The number of patients with confirmed or unconfirmed OR (partial or complete response) is presented. Duration of SD for patients with best overall response = SD was defined as the time from the day of first study treatment to the start of radiologic disease progression or death. If the patient did not have a radiological disease progression or death, the duration of SD was defined as the time from the day of first study treatment to the date of the last SD assessment.

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

OR or SD Assessed by Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST). The number of patients with confirmed or unconfirmed OR (partial or complete response) is presented. Duration of SD for patients with best overall response = SD was defined as the time from the day of first study treatment to the start of radiologic disease progression or death. If the patient did not have a radiological disease progression or death, the duration of SD was defined as the time from the day of first study treatment to the date of the last SD assessment.

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

OR or SD Assessed by Response Evaluation Criteria in Lymphomas 2017 (RECIL 2017)

Time to Progression (TTP) of Disease.

Based on time of enrollment to first evidence of progression on imaging studies, as assessed by RECIST v1.1, RECIL 2017, or iRECIST, depending on tumor type. The numbers shown below correspond to the values related to RECIST v1.1.

Area Under the Concentration-time Curve in a Dosing Interval (AUC).

The AUC after first dose was estimated using non-compartmental methods. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.

Maximum Concentration (Cmax)

Outcome measure after first dose was derived from observed data. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.

Time to Reach Maximum Concentration (Tmax)

Trough Concentration (Ctrough)

Terminal Elimination Half-life (T½)

Outcome measure after first dose was estimated using non-compartmental methods. Blood samples for PK analysis were taken at the following timepoints: before the start of the infusion, at the end of the infusion and at 2, 4, 8, 24, 48 and 168 hours after the end of the infusion. Actual timepoints were recorded.

Clearance (CL)

Full Information

NCT ID

NCT03489343

First Posted

March 26, 2018

Last Updated

October 11, 2021

Sponsor

Symphogen A/S

1. Study Identification

Unique Protocol Identification Number

NCT03489343

Brief Title

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

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Completed

Study Start Date

May 24, 2018 (Actual)

Primary Completion Date

June 3, 2020 (Actual)

Study Completion Date

June 3, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Symphogen A/S

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Cancer, Solid Tumor, Lymphoma

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sym023 0.03 mg/kg

Arm Type

Experimental

Arm Description

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

Arm Title

Sym023 0.1 mg/kg

Arm Type

Experimental

Arm Description

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

Arm Title

Sym023 0.3 mg/kg

Arm Type

Experimental

Arm Description

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

Arm Title

Sym023 1.0 mg/kg

Arm Type

Experimental

Arm Description

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

Arm Title

Sym023 3.0 mg/kg

Arm Type

Experimental

Arm Description

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

Arm Title

Sym023 10.0 mg/kg

Arm Type

Experimental

Arm Description

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

Arm Title

Sym023 20.0 mg/kg

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Sym023

Other Intervention Name(s)

Anti-TIM-3

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame

28 days

Secondary Outcome Measure Information:

Title

Evaluation of the Immunogenicity of Sym023.

Description

Serum sampling to assess the potential for anti-drug antibody (ADA) formation. The number of patients with positive samples at indicated visits is presented.

Time Frame

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

Title

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

Description

Time Frame

24 months

Title

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

Description

Time Frame

24 months

Title

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

Description

OR or SD Assessed by Response Evaluation Criteria in Lymphomas 2017 (RECIL 2017)

Time Frame

24 months

Title

Time to Progression (TTP) of Disease.

Description

Time Frame

24 months

Title

Area Under the Concentration-time Curve in a Dosing Interval (AUC).

Description

Time Frame