Metastatic CancerPhase 1NCT03489343
Sym023 (Anti-TIM-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas
A Phase 1 study testing Sym023 in people with Metastatic Cancer and Solid Tumor, run by Symphogen A/S at 4 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Cancer, Solid Tumor, Lymphoma
- What is being tested?
- Sym023
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 24 May 2018to 3 Jun 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
United States3 sites
South Texas Accelerated Research Therapeutics (START) Midwest
Grand Rapids, Michigan, 49503
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
NEXT Oncology
San Antonio, Texas, 78240
About this study
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
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.
Read the 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.
- Conditions
- Metastatic Cancer, Solid Tumor, Lymphoma
- Being tested
- Sym023
- Keywords
- Locally advanced/unresectable, Metastatic solid tumor, Lymphoma, Anti-TIM-3, TIM-3, TIM3
- Medical subject headings
- Neoplasm Metastasis, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sym023Drug
Also called Anti-TIM-3
Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.
| Study group | Role | What they receive |
|---|---|---|
| Sym023 0.03 mg/kg | Experimental | Sym023 was administered at a dose of 0.03 mg/kg by intravenous infusion Receives: Drug: Sym023 |
| Sym023 0.1 mg/kg | Experimental | Sym023 was administered at a dose of 0.1 mg/kg by intravenous infusion Receives: Drug: Sym023 |
| Sym023 0.3 mg/kg | Experimental | Sym023 was administered at a dose of 0.3 mg/kg by intravenous infusion Receives: Drug: Sym023 |
| Sym023 1.0 mg/kg | Experimental | Sym023 was administered at a dose of 1.0 mg/kg by intravenous infusion Receives: Drug: Sym023 |
| Sym023 3.0 mg/kg | Experimental | Sym023 was administered at a dose of 3.0 mg/kg by intravenous infusion Receives: Drug: Sym023 |
| Sym023 10.0 mg/kg | Experimental | Sym023 was administered at a dose of 10.0 mg/kg by intravenous infusion Receives: Drug: Sym023 |
| Sym023 20.0 mg/kg | Experimental | Sym023 was administered at a dose of 20.0 mg/kg by intravenous infusion Receives: Drug: Sym023 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 days
Secondary outcomes (11)
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.
Measured: Baseline up to 6-months follow-up, approximately 1 year
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.
Measured: 24 months
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.
Measured: 24 months
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)
Measured: 24 months
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.
Measured: 24 months
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.
Measured: From before the start of the infusion to 168 hours after the end of the infusion
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.
Measured: From before the start of the infusion to 168 hours after the end of the infusion
Time to Reach Maximum Concentration (Tmax)
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.
Measured: From before the start of the infusion to 168 hours after the end of the infusion
Trough Concentration (Ctrough)
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.
Measured: From before the start of the infusion to 168 hours after the end of the infusion
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.
Measured: From before the start of the infusion to 168 hours after the end of the infusion
Clearance (CL)
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.
Measured: From before the start of the infusion to 168 hours after the end of the infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2018
- Study start24 May 2018
- Primary completion3 Jun 2020
- Study completion3 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Symphogen A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lillian Siu, MD, FRCPC, Principal investigator, Princess Margaret Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03489343
- Sponsor's protocol ID
- Sym023-01
- Status last verified
- Aug 2021
- First submitted
- 26 Mar 2018
- Last updated
- 12 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03489343
- Acronym / sponsor ID
- Sym023-01
- Conditions
- Metastatic Cancer, Solid Tumor, Lymphoma
- Keywords
- Locally advanced/unresectable, Metastatic solid tumor, Lymphoma, Anti-TIM-3, TIM-3, TIM3
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Symphogen A/SIndustry (pharma, biotech, devices)
- Study start
- 24 May 2018 (actual)
- Primary completion
- 3 Jun 2020 (actual)
- Study completion
- 3 Jun 2020 (actual)
- First posted
- 5 Apr 2018 (actual)
- Results
- Posted 12 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Sym023 0.03 mg/kg | Experimental | Drug: Sym023Sym023 was administered at a dose of 0.03 mg/kg by intravenous infusion |
| Sym023 0.1 mg/kg | Experimental | Drug: Sym023Sym023 was administered at a dose of 0.1 mg/kg by intravenous infusion |
| Sym023 0.3 mg/kg | Experimental | Drug: Sym023Sym023 was administered at a dose of 0.3 mg/kg by intravenous infusion |
| Sym023 1.0 mg/kg | Experimental | Drug: Sym023Sym023 was administered at a dose of 1.0 mg/kg by intravenous infusion |
| Sym023 3.0 mg/kg | Experimental | Drug: Sym023Sym023 was administered at a dose of 3.0 mg/kg by intravenous infusion |
| Sym023 10.0 mg/kg | Experimental | Drug: Sym023Sym023 was administered at a dose of 10.0 mg/kg by intravenous infusion |
| Sym023 20.0 mg/kg | Experimental | Drug: Sym023Sym023 was administered at a dose of 20.0 mg/kg by intravenous infusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sym023Also: Anti-TIM-3Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells. | Drug | 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 |
Primary outcome
Assessment of Treatment Emergent Adverse Events (AEs) Meeting Dose-limiting Toxicity (DLT) Criteria.
Time frame: 28 days
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.
11 secondary outcomes
Evaluation of the Immunogenicity of Sym023.
Time frame: Baseline up to 6-months follow-up, approximately 1 year
Evaluation of Objective Response (OR) or Stable Disease (SD) by RECIST v1.1
Time frame: 24 months
Evaluation of Objective Response (OR) or Stable Disease (SD) by iRECIST
Time frame: 24 months
Evaluation of Objective Response (OR) or Stable Disease (SD) by RECIL 2017.
Time frame: 24 months
Time to Progression (TTP) of Disease.
Time frame: 24 months
Area Under the Concentration-time Curve in a Dosing Interval (AUC).
Time frame: From before the start of the infusion to 168 hours after the end of the infusion
Maximum Concentration (Cmax)
Time frame: From before the start of the infusion to 168 hours after the end of the infusion
Time to Reach Maximum Concentration (Tmax)
Time frame: From before the start of the infusion to 168 hours after the end of the infusion
Trough Concentration (Ctrough)
Time frame: From before the start of the infusion to 168 hours after the end of the infusion
Terminal Elimination Half-life (T½)
Time frame: From before the start of the infusion to 168 hours after the end of the infusion
Clearance (CL)
Time frame: From before the start of the infusion to 168 hours after the end of the infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lillian Siu, MD, FRCPC principal investigator
Princess Margaret Cancer Centre
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sym023 in people with Metastatic Cancer and Solid Tumor, run by Symphogen A/S at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of Treatment Emergent Adverse Events (AEs) Meeting Dose-limiting Toxicity (DLT) Criteria. (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2021.