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

• Sponsor: Symphogen A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03489343
• Collaborator: (none)
• Enrollment: 24
• Locations: 4
• Arms: 7
• Actual Duration (Months): 24.3
• Patients Per Site: 6
• Patients Per Site Per Month: 0.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Cancer; Solid Tumor; Lymphoma	Drug: Sym023	Phase 1

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

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 24, 2018
• Actual Primary Completion Date: Jun 3, 2020
• Actual Study Completion Date: Jun 3, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sym023 0.03 mg/kg Sym023 was administered at a dose of 0.03 mg/kg by intravenous infusion	Drug: Sym023; Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.; Other Names: Anti-TIM-3
Experimental: Sym023 0.1 mg/kg Sym023 was administered at a dose of 0.1 mg/kg by intravenous infusion	Drug: Sym023; Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.; Other Names: Anti-TIM-3
Experimental: Sym023 0.3 mg/kg Sym023 was administered at a dose of 0.3 mg/kg by intravenous infusion	Drug: Sym023; Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.; Other Names: Anti-TIM-3
Experimental: Sym023 1.0 mg/kg Sym023 was administered at a dose of 1.0 mg/kg by intravenous infusion	Drug: Sym023; Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.; Other Names: Anti-TIM-3
Experimental: Sym023 3.0 mg/kg Sym023 was administered at a dose of 3.0 mg/kg by intravenous infusion	Drug: Sym023; Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.; Other Names: Anti-TIM-3
Experimental: Sym023 10.0 mg/kg Sym023 was administered at a dose of 10.0 mg/kg by intravenous infusion	Drug: Sym023; Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.; Other Names: Anti-TIM-3
Experimental: Sym023 20.0 mg/kg Sym023 was administered at a dose of 20.0 mg/kg by intravenous infusion	Drug: Sym023; Sym023 is a recombinant, fully human antibody that binds TIM-3 and induces activation of immune cells.; Other Names: Anti-TIM-3

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

1. Evaluation of the Immunogenicity of Sym023. [Baseline up to 6-months follow-up, approximately 1 year]

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

2. Evaluation of Objective Response (OR) or Stable Disease (SD) by RECIST v1.1 [24 months]

   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.

3. Evaluation of Objective Response (OR) or Stable Disease (SD) by iRECIST [24 months]

   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.

4. Evaluation of Objective Response (OR) or Stable Disease (SD) by RECIL 2017. [24 months]

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

5. Time to Progression (TTP) of Disease. [24 months]

   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.

6. Area Under the Concentration-time Curve in a Dosing Interval (AUC). [From before the start of the infusion to 168 hours after the end of the infusion]

   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.

7. Maximum Concentration (Cmax) [From before the start of the infusion to 168 hours after the end of the infusion]

   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.

8. Time to Reach Maximum Concentration (Tmax) [From before the start of the infusion to 168 hours after the end of the infusion]

   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.

9. Trough Concentration (Ctrough) [From before the start of the infusion to 168 hours after the end of the infusion]

   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.

10. Terminal Elimination Half-life (T½) [From before the start of the infusion to 168 hours after the end of the infusion]

    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.

11. Clearance (CL) [From before the start of the infusion to 168 hours after the end of the infusion]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	South Texas Accelerated Research Therapeutics (START) Midwest	Grand Rapids	Michigan	United States	49503
2	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
3	NEXT Oncology	San Antonio	Texas	United States	78240
4	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2M9

Sponsors and Collaborators

• Symphogen A/S

Investigators

• Principal Investigator: Lillian Siu, MD, FRCPC, Princess Margaret Cancer Centre

Study Documents (Full-Text)

• Study Protocol - May 2, 2019
• Statistical Analysis Plan - Jun 26, 2020

More Information

Publications

None provided.

• Responsible Party: Symphogen A/S
• ClinicalTrials.gov Identifier: NCT03489343
• Other Study ID Numbers: Sym023-01
• First Posted: Apr 5, 2018
• Last Update Posted: Oct 12, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Symphogen A/S: Locally advanced/unresectable; Metastatic solid tumor; Lymphoma; Anti-TIM-3; TIM-3; TIM3
• Additional relevant MeSH terms: Lymphoma

Study Results

Participant Flow

Arm/Group Title	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/Group Description	Sym023 0.03 mg/kg intravenous infusion once every 2 weeks	Sym023 0.1 mg/kg intravenous infusion once every 2 weeks	Sym023 0.3 mg/kg intravenous infusion once every 2 weeks	Sym023 1.0 mg/kg intravenous infusion once every 2 weeks	Sym023 3.0 mg/kg intravenous infusion once every 2 weeks	Sym023 10.0 mg/kg intravenous infusion once every 2 weeks	Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Period Title: Overall Study
STARTED	1	1	3	3	3	7	6
COMPLETED	0	0	0	0	0	0	0
NOT COMPLETED	1	1	3	3	3	7	6

Baseline Characteristics

Arm/Group Title	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	Total
Arm/Group Description	Sym023 0.03 mg/kg intravenous infusion once every 2 weeks	Sym023 0.1 mg/kg intravenous infusion once every 2 weeks	Sym023 0.3 mg/kg intravenous infusion once every 2 weeks	Sym023 1.0 mg/kg intravenous infusion once every 2 weeks	Sym023 3.0 mg/kg intravenous infusion once every 2 weeks	Sym023 10.0 mg/kg intravenous infusion once every 2 weeks	Sym023 20.0 mg/kg intravenous infusion once every 2 weeks	Total of all reporting groups
Overall Participants	1	1	3	3	3	7	6	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	1 100%	1 100%	2 66.7%	1 33.3%	1 33.3%	5 71.4%	5 83.3%	16 66.7%
>=65 years	0 0%	0 0%	1 33.3%	2 66.7%	2 66.7%	2 28.6%	1 16.7%	8 33.3%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64	64	62	66	71	54	61	63
Sex: Female, Male (Count of Participants)
Female	0 0%	1 100%	2 66.7%	2 66.7%	3 100%	4 57.1%	4 66.7%	16 66.7%
Male	1 100%	0 0%	1 33.3%	1 33.3%	0 0%	3 42.9%	2 33.3%	8 33.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	1 100%	1 100%	3 100%	3 100%	2 66.7%	7 100%	6 100%	23 95.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%	1 4.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	3 42.9%	0 0%	3 12.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	2 28.6%	1 16.7%	3 12.5%
White	1 100%	1 100%	3 100%	3 100%	2 66.7%	2 28.6%	5 83.3%	17 70.8%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%	1 4.2%
Region of Enrollment (participants) [Number]
Canada	0 0%	0 0%	0 0%	1 33.3%	1 33.3%	2 28.6%	1 16.7%	5 20.8%
United States	1 100%	1 100%	3 100%	2 66.7%	2 66.7%	5 71.4%	5 83.3%	19 79.2%
ECOG PS (Count of Participants)
1	1 100%	1 100%	2 66.7%	2 66.7%	3 100%	6 85.7%	4 66.7%	19 79.2%
0	0 0%	0 0%	1 33.3%	1 33.3%	0 0%	1 14.3%	2 33.3%	5 20.8%

Outcome Measures

1. Primary Outcome

Title	Assessment of Treatment Emergent Adverse Events (AEs) Meeting Dose-limiting Toxicity (DLT) Criteria.
Description	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.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

DLT analysis set of patients who completed treatment dosing in a 4-week (28 day) period that was Cycle 1. One patient out of 7 patients in Group 10mg/kg did not complete Cycle 1 and are not included in the "participants analyzed"

Arm/Group Title	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/Group Description	Sym023 0.03 mg/kg intravenous infusion once every 2 weeks	Sym023 0.1 mg/kg intravenous infusion once every 2 weeks	Sym023 0.3 mg/kg intravenous infusion once every 2 weeks	Sym023 1.0 mg/kg intravenous infusion once every 2 weeks	Sym023 3.0 mg/kg intravenous infusion once every 2 weeks	Sym023 10.0 mg/kg intravenous infusion once every 2 weeks	Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Measure Participants	1	1	3	3	3	6	6
Number [Number of DLTs]	0	0	0	0	0	0	0

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Full analysis set of all randomised and treated patients

Arm/Group Title	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/Group Description	Sym023 0.03 mg/kg intravenous infusion once every 2 weeks	Sym023 0.1 mg/kg intravenous infusion once every 2 weeks	Sym023 0.3 mg/kg intravenous infusion once every 2 weeks	Sym023 1.0 mg/kg intravenous infusion once every 2 weeks	Sym023 3.0 mg/kg intravenous infusion once every 2 weeks	Sym023 10.0 mg/kg intravenous infusion once every 2 weeks	Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Measure Participants	1	1	3	3	3	7	6
Cycle 1 days 1 and 15	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Cycle 2 day 1	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Cycle 3 days 1 and 15	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Cycle 4 days 1 and 15	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Cycle 5 day 1	0 0%	1 100%	0 0%	1 33.3%	0 0%	0 0%	0 0%
Cycle 6 day 1	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Cycle 7 day 1	0 0%	1 100%	0 0%	0 0%	0 0%	0 0%	0 0%
End of treatment	0 0%	1 100%	1 33.3%	1 33.3%	0 0%	0 0%	0 0%
1-month follow up	0 0%	1 100%	1 33.3%	1 33.3%	0 0%	0 0%	0 0%
3-month follow up	0 0%	0 0%	0 0%	1 33.3%	0 0%	0 0%	0 0%

3. Secondary Outcome

Title	Evaluation of Objective Response (OR) or Stable Disease (SD) by RECIST v1.1
Description	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.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Full analysis set of randomised and treated patients who was evaluable for response. One patient out of 7 in group 10mg/kg was not evaluable for response

Arm/Group Title	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/Group Description	Sym023 0.03 mg/kg intravenous infusion once every 2 weeks	Sym023 0.1 mg/kg intravenous infusion once every 2 weeks	Sym023 0.3 mg/kg intravenous infusion once every 2 weeks	Sym023 1.0 mg/kg intravenous infusion once every 2 weeks	Sym023 3.0 mg/kg intravenous infusion once every 2 weeks	Sym023 10.0 mg/kg intravenous infusion once every 2 weeks	Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Measure Participants	1	1	3	3	3	6	6
OR rate	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
SD >16 weeks	0 0%	1 100%	0 0%	0 0%	0 0%	0 0%	2 33.3%
SD ≤16 weeks	0 0%	0 0%	0 0%	2 66.7%	2 66.7%	0 0%	3 50%

4. Secondary Outcome

Title	Evaluation of Objective Response (OR) or Stable Disease (SD) by iRECIST
Description	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.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Full analysis set of randomised and treated patients who were evaluable for response. One patient out of 7 in group 10mg/kg was not evaluable for response

Arm/Group Title	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/Group Description	Sym023 0.03 mg/kg intravenous infusion once every 2 weeks	Sym023 0.1 mg/kg intravenous infusion once every 2 weeks	Sym023 0.3 mg/kg intravenous infusion once every 2 weeks	Sym023 1.0 mg/kg intravenous infusion once every 2 weeks	Sym023 3.0 mg/kg intravenous infusion once every 2 weeks	Sym023 10.0 mg/kg intravenous infusion once every 2 weeks	Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Measure Participants	1	1	3	3	3	6	6
OR rate	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
iSD >16 weeks	0 0%	1 100%	0 0%	1 33.3%	1 33.3%	0 0%	1 16.7%
iSD ≤16 weeks	0 0%	0 0%	0 0%	2 66.7%	1 33.3%	0 0%	4 66.7%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

No lymphomas were recorded in this trial, therefore it was not possible to do the RECIL evaluation.

Arm/Group Title	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/Group Description	Sym023 0.03 mg/kg intravenous infusion once every 2 weeks	Sym023 0.1 mg/kg intravenous infusion once every 2 weeks	Sym023 0.3 mg/kg intravenous infusion once every 2 weeks	Sym023 1.0 mg/kg intravenous infusion once every 2 weeks	Sym023 3.0 mg/kg intravenous infusion once every 2 weeks	Sym023 10.0 mg/kg intravenous infusion once every 2 weeks	Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Measure Participants	0	0	0	0	0	0	0

6. Secondary Outcome

Title	Time to Progression (TTP) of Disease.
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.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

The full analysis set of randomized and treated patients who were evaluable for response. One patient out of 7 in group 10mg/kg was not evaluable for response or time to progression (TTP) as the patient left trial due to Adverse Event

Arm/Group Title	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/Group Description	Sym023 0.03 mg/kg intravenous infusion once every 2 weeks	Sym023 0.1 mg/kg intravenous infusion once every 2 weeks	Sym023 0.3 mg/kg intravenous infusion once every 2 weeks	Sym023 1.0 mg/kg intravenous infusion once every 2 weeks	Sym023 3.0 mg/kg intravenous infusion once every 2 weeks	Sym023 10.0 mg/kg intravenous infusion once every 2 weeks	Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Measure Participants	1	1	3	3	3	6	6
Median (Full Range) [months]	1.81	7.89	1.18	3.48	1.28	1.68	5.36

7. Secondary Outcome

Title	Area Under the Concentration-time Curve in a Dosing Interval (AUC).
Description	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.
Time Frame	From before the start of the infusion to 168 hours after the end of the infusion

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis set (same as the full analysis set) of all randomised and treated patients

Arm/Group Title	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/Group Description	Sym023 0.03 mg/kg intravenous infusion once every 2 weeks	Sym023 0.1 mg/kg intravenous infusion once every 2 weeks	Sym023 0.3 mg/kg intravenous infusion once every 2 weeks	Sym023 1.0 mg/kg intravenous infusion once every 2 weeks	Sym023 3.0 mg/kg intravenous infusion once every 2 weeks	Sym023 10.0 mg/kg intravenous infusion once every 2 weeks	Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Measure Participants	1	1	3	3	3	7	6
Mean (Full Range) [h*μg/mL]	70	176	878	3193	8062	30581	77262

8. Secondary Outcome

Title	Maximum Concentration (Cmax)
Description	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 Frame	From before the start of the infusion to 168 hours after the end of the infusion

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis set (same as the full analysis set) of all randomised and treated patients

Arm/Group Title	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/Group Description	Sym023 0.03 mg/kg intravenous infusion once every 2 weeks	Sym023 0.1 mg/kg intravenous infusion once every 2 weeks	Sym023 0.3 mg/kg intravenous infusion once every 2 weeks	Sym023 1.0 mg/kg intravenous infusion once every 2 weeks	Sym023 3.0 mg/kg intravenous infusion once every 2 weeks	Sym023 10.0 mg/kg intravenous infusion once every 2 weeks	Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Measure Participants	1	1	3	3	3	7	6
Mean (Full Range) [μg/mL]	0.85	1.98	7.94	23.71	68.03	232.11	470.24

9. Secondary Outcome

Title	Time to Reach Maximum Concentration (Tmax)
Description	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 Frame	From before the start of the infusion to 168 hours after the end of the infusion

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis set (same as the full analysis set) of all randomised and treated patients

Arm/Group Title	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/Group Description	Sym023 0.03 mg/kg intravenous infusion once every 2 weeks	Sym023 0.1 mg/kg intravenous infusion once every 2 weeks	Sym023 0.3 mg/kg intravenous infusion once every 2 weeks	Sym023 1.0 mg/kg intravenous infusion once every 2 weeks	Sym023 3.0 mg/kg intravenous infusion once every 2 weeks	Sym023 10.0 mg/kg intravenous infusion once every 2 weeks	Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Measure Participants	1	1	3	3	3	7	6
Mean (Full Range) [hours]	4.5	0.6	1.2	4.5	1.8	3.4	7.3

10. Secondary Outcome

Title	Trough Concentration (Ctrough)
Description	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 Frame	From before the start of the infusion to 168 hours after the end of the infusion

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis set (same as the full analysis set) of all randomized and treated patients. Data for cohort 0.03mg/kg: Ctrough at 168 hours were below the limit of quantification, hence no reported data

Arm/Group Title	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/Group Description	Sym023 0.03 mg/kg intravenous infusion once every 2 weeks	Sym023 0.1 mg/kg intravenous infusion once every 2 weeks	Sym023 0.3 mg/kg intravenous infusion once every 2 weeks	Sym023 1.0 mg/kg intravenous infusion once every 2 weeks	Sym023 3.0 mg/kg intravenous infusion once every 2 weeks	Sym023 10.0 mg/kg intravenous infusion once every 2 weeks	Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Measure Participants	1	1	3	3	3	5	6
Mean (Full Range) [μg/mL]	NA	0.16	1.26	6.39	12.88	74.33	146.96

11. Secondary Outcome

Title	Terminal Elimination Half-life (T½)
Description	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.
Time Frame	From before the start of the infusion to 168 hours after the end of the infusion

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis set (same as the full analysis set) of all randomised and treated patients. Data for cohort 0.03mg/kg: T½ could not be accurately calculated due to few datapoint within the elimination period

Arm/Group Title	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/Group Description	Sym023 0.03 mg/kg intravenous infusion once every 2 weeks	Sym023 0.1 mg/kg intravenous infusion once every 2 weeks	Sym023 0.3 mg/kg intravenous infusion once every 2 weeks	Sym023 1.0 mg/kg intravenous infusion once every 2 weeks	Sym023 3.0 mg/kg intravenous infusion once every 2 weeks	Sym023 10.0 mg/kg intravenous infusion once every 2 weeks	Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Measure Participants	1	1	3	0	2	2	1
Mean (Full Range) [hours]	NA	105.10	153.49	140.60	185.22	203.07

12. Secondary Outcome

Title	Clearance (CL)
Description	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.
Time Frame	From before the start of the infusion to 168 hours after the end of the infusion

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis set (same as the full analysis set) of all randomized and treated patients. Data for cohort 0.03mg/kg: Clearence could not be accurately calculated since too few datapoint within the elimination period

Arm/Group Title	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/Group Description	Sym023 0.03 mg/kg intravenous infusion once every 2 weeks	Sym023 0.1 mg/kg intravenous infusion once every 2 weeks	Sym023 0.3 mg/kg intravenous infusion once every 2 weeks	Sym023 1.0 mg/kg intravenous infusion once every 2 weeks	Sym023 3.0 mg/kg intravenous infusion once every 2 weeks	Sym023 10.0 mg/kg intravenous infusion once every 2 weeks	Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
Measure Participants	0	1	1	0	1	0	0
Mean (Full Range) [mL/h)/kg]	0.501	0.364	0.582

Adverse Events

Time Frame	24 months
Adverse Event Reporting Description	Only treatment-emergent adverse events (AEs) are presented in clinicaltrials.gov, defined as AEs with onset dates on or after the first dose of study medication or AEs that occurred before the first dose of study medication and increased in severity after the first dose of study medication up to the last dose of study drug plus 30 days.
Arm/Group Title	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/Group Description	Sym023 0.03 mg/kg intravenous infusion once every 2 weeks		Sym023 0.1 mg/kg intravenous infusion once every 2 weeks		Sym023 0.3 mg/kg intravenous infusion once every 2 weeks		Sym023 1.0 mg/kg intravenous infusion once every 2 weeks		Sym023 3.0 mg/kg intravenous infusion once every 2 weeks		Sym023 10.0 mg/kg intravenous infusion once every 2 weeks		Sym023 20.0 mg/kg intravenous infusion once every 2 weeks
All Cause Mortality
	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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)		3/3 (100%)		0/3 (0%)		2/3 (66.7%)		1/7 (14.3%)		1/6 (16.7%)
Serious Adverse Events
	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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		1/1 (100%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		2/7 (28.6%)		1/6 (16.7%)
Investigations
Lipase increased	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0
Musculoskeletal and connective tissue disorders
Immune-mediated arthritis	0/1 (0%)	0	1/1 (100%)	1	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0
Pathological fracture	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0
Back pain	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1
Nervous system disorders
Spinal cord compression	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1
Other (Not Including Serious) Adverse Events
	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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		1/1 (100%)		3/3 (100%)		3/3 (100%)		3/3 (100%)		7/7 (100%)		5/6 (83.3%)
Blood and lymphatic system disorders
Anemia	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	1/3 (33.3%)	1	1/7 (14.3%)	1	2/6 (33.3%)	3
Gastrointestinal disorders
Constipation	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	1/7 (14.3%)	1	1/6 (16.7%)	1
Nausea	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	1/6 (16.7%)	2
Diarrhoea	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	2/7 (28.6%)	2	0/6 (0%)	0
Pyrexia	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/7 (14.3%)	1	0/6 (0%)	0
General disorders
Fatigue	1/1 (100%)	1	1/1 (100%)	4	2/3 (66.7%)	3	1/3 (33.3%)	1	1/3 (33.3%)	2	2/7 (28.6%)	2	1/6 (16.7%)	1
Hepatobiliary disorders
Hyperbilirubinemia	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	3	1/3 (33.3%)	1	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0
Infections and infestations
Urinary tract infection	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	1	0/7 (0%)	0	1/6 (16.7%)	1
Pneumonia	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0
Investigations
Lipase increased	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	2	0/6 (0%)	0
Lymphocyte count decreased	1/1 (100%)	3	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0
Metabolism and nutrition disorders
Hypophosphatemia	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	2	1/3 (33.3%)	3	0/3 (0%)	0	1/7 (14.3%)	1	1/6 (16.7%)	1
Decreased appetite	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	1/6 (16.7%)	1
Hyponatremia	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	1/6 (16.7%)	1
Musculoskeletal and connective tissue disorders
Back pain	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1
Pain in extremity	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	1/6 (16.7%)	1
Psychiatric disorders
Anxiety	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	2/6 (33.3%)	2
Respiratory, thoracic and mediastinal disorders
Cough	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	2	0/3 (0%)	0	1/3 (33.3%)	1	2/7 (28.6%)	2	0/6 (0%)	0
Vascular disorders
Hypertension	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	2/7 (28.6%)	2	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.