Description:
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.
Title
- Brief Title: Sym022 (Anti-LAG-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 Sym022 (Anti-LAG-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas
Clinical Trial IDs
- ORG STUDY ID:
Sym022-01
- NCT ID:
NCT03489369
Conditions
- Metastatic Cancer
- Solid Tumor
- Lymphoma
Interventions
Drug | Synonyms | Arms |
---|
Sym022 | Anti-LAG-3 | Sym022 |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Sym022 | Experimental | Sym022 will be administered at up to 4 planned dose levels. | |
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Assessment of Treatment Related Adverse Events (AEs). |
Time Frame: | 19 months |
Safety Issue: | |
Description: | Assess the safety, tolerability and dose-limiting toxicities of Sym022 on a Q2W schedule to establish the MTD and/or RP2D. |
Secondary Outcome Measures
Measure: | Evaluation of the Immunogenicity of Sym022. |
Time Frame: | 19 months |
Safety Issue: | |
Description: | Serum sampling and incidence (%) per dose level to assess the potential for anti-drug antibody (ADA) formation. Count of participants show the number of participants who were tested positive for anti-Sym022 ADA. |
Measure: | Evaluation of Objective Response (OR) or Stable Disease (SD). |
Time Frame: | 13 months |
Safety Issue: | |
Description: | Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), Response Evaluation Criteria in Lymphomas 2017 (RECIL 2017), or Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST), depending on tumor type. The numbers shown below correspond to the values related to RECIST v1.1. |
Measure: | Time to Progression (TTP) of Disease. |
Time Frame: | 13 months |
Safety Issue: | |
Description: | 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. |
Measure: | Area Under the Concentration-time Curve in a Dosing Interval (AUC). |
Time Frame: | 19 months |
Safety Issue: | |
Description: | Will be estimated using non-compartmental methods and actual timepoints. |
Measure: | Maximum Concentration (Cmax) |
Time Frame: | 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week) |
Safety Issue: | |
Description: | Will be derived from observed data. |
Measure: | Time to Reach Maximum Concentration (Tmax) |
Time Frame: | 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week) |
Safety Issue: | |
Description: | Will be derived from observed data. |
Measure: | Trough Concentration (Ctrough) |
Time Frame: | 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week) |
Safety Issue: | |
Description: | Will be derived from observed data. |
Measure: | Terminal Elimination Half-life (T½) |
Time Frame: | 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week) |
Safety Issue: | |
Description: | Will be estimated using non-compartmental methods and actual timepoints. |
Measure: | Clearance (CL) |
Time Frame: | 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week) |
Safety Issue: | |
Description: | Will be estimated using non-compartmental methods and actual timepoints. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Symphogen A/S |
Trial Keywords
- Locally advanced/unresectable
- Metastatic solid tumor
- Lymphoma
- Anti-LAG-3
- LAG-3
- LAG3
Last Updated
February 18, 2021