Trial Outcomes & Findings for Sym004 in Combination With FOLFIRI in Metastatic Colorectal Cancer Patients (NCT NCT02568046)

Last Updated: 2019-03-26

Results Overview

AEs were coded according to the Medical Dictionary for Regulatory Activities (MedDRA) classification. The incidence and type of AEs (e.g., treatment-emergent AE \[TEAE\]) were summarized according to MedDRA system organ classes and preferred terms. An AE was considered as treatment-emergent if it occurred after the first treatment administration.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

10 participants

Primary outcome timeframe

15 months

Results posted on

2019-03-26

Participant Flow

The first patient was enrolled in March 2016. In January 2017, the trial was terminated early and enrollment was prematurely discontinued.

Participant milestones

Participant milestones
Measure	Dose Level 1: Sym004 12 mg/kg + FOLFIRI Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR). The standard FOLFIRI regimen consists of Irinotecan (180 mg/m\^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m\^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m\^2 IV bolus, then 2400 mg/m\^2 infused over 46 hours).	Dose Level -1: Sym004 9 mg/kg + FOLFIRI Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR). The standard FOLFIRI regimen consists of Irinotecan (180 mg/m\^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m\^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m\^2 IV bolus, then 2400 mg/m\^2 infused over 46 hours).
Overall Study STARTED	5	5
Overall Study COMPLETED	0	2
Overall Study NOT COMPLETED	5	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose Level 1: Sym004 12 mg/kg + FOLFIRI Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR). The standard FOLFIRI regimen consists of Irinotecan (180 mg/m\^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m\^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m\^2 IV bolus, then 2400 mg/m\^2 infused over 46 hours).	Dose Level -1: Sym004 9 mg/kg + FOLFIRI Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR). The standard FOLFIRI regimen consists of Irinotecan (180 mg/m\^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m\^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m\^2 IV bolus, then 2400 mg/m\^2 infused over 46 hours).
Overall Study Adverse Event	0	1
Overall Study Death	2	0
Overall Study Progressive Disease	1	0
Overall Study Withdrawal by Subject	2	1
Overall Study Other Events	0	1

Baseline Characteristics

Sym004 in Combination With FOLFIRI in Metastatic Colorectal Cancer Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Level 1: Sym004 12 mg/kg + FOLFIRI n=5 Participants Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR). The standard FOLFIRI regimen consists of Irinotecan (180 mg/m\^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m\^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m\^2 IV bolus, then 2400 mg/m\^2 infused over 46 hours).	Dose Level -1: Sym004 9 mg/kg + FOLFIRI n=5 Participants Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR). The standard FOLFIRI regimen consists of Irinotecan (180 mg/m\^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m\^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m\^2 IV bolus, then 2400 mg/m\^2 infused over 46 hours).	Total n=10 Participants Total of all reporting groups
Age, Continuous	69.3 years STANDARD_DEVIATION 8.55 • n=99 Participants	61.1 years STANDARD_DEVIATION 9.95 • n=107 Participants	65.2 years STANDARD_DEVIATION 9.76 • n=206 Participants
Sex: Female, Male Female	2 Participants n=99 Participants	2 Participants n=107 Participants	4 Participants n=206 Participants
Sex: Female, Male Male	3 Participants n=99 Participants	3 Participants n=107 Participants	6 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=99 Participants	2 Participants n=107 Participants	3 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=99 Participants	3 Participants n=107 Participants	7 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) White	5 Participants n=99 Participants	5 Participants n=107 Participants	10 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United States	3 Participants n=99 Participants	2 Participants n=107 Participants	5 Participants n=206 Participants
Region of Enrollment Spain	2 Participants n=99 Participants	3 Participants n=107 Participants	5 Participants n=206 Participants
Height	170.4 centimeters (cm) STANDARD_DEVIATION 8.57 • n=99 Participants	171.3 centimeters (cm) STANDARD_DEVIATION 4.47 • n=107 Participants	170.9 centimeters (cm) STANDARD_DEVIATION 6.46 • n=206 Participants
Weight	76.6 kilograms (kg) STANDARD_DEVIATION 11.97 • n=99 Participants	82.5 kilograms (kg) STANDARD_DEVIATION 16.10 • n=107 Participants	79.6 kilograms (kg) STANDARD_DEVIATION 13.73 • n=206 Participants
Body Mass Index (BMI)	26.5 kg/m^2 STANDARD_DEVIATION 4.20 • n=99 Participants	28.0 kg/m^2 STANDARD_DEVIATION 4.52 • n=107 Participants	27.3 kg/m^2 STANDARD_DEVIATION 4.19 • n=206 Participants
Body Surface Area (BSA)	1.9 m^2 STANDARD_DEVIATION 0.17 • n=99 Participants	2.0 m^2 STANDARD_DEVIATION 0.24 • n=107 Participants	1.9 m^2 STANDARD_DEVIATION 0.20 • n=206 Participants

PRIMARY outcome

Timeframe: 15 months

Population: All safety analyses were conducted using the Full Analysis Set (FAS) population, defined as all patients who received at least 1 dose of trial treatment.

Outcome measures

Outcome measures
Measure	Dose Level 1: Sym004 12 mg/kg + FOLFIRI n=5 Participants Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR). The standard FOLFIRI regimen consists of Irinotecan (180 mg/m\^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m\^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m\^2 IV bolus, then 2400 mg/m\^2 infused over 46 hours).	Dose Level -1: Sym004 9 mg/kg + FOLFIRI n=5 Participants Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR). The standard FOLFIRI regimen consists of Irinotecan (180 mg/m\^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m\^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m\^2 IV bolus, then 2400 mg/m\^2 infused over 46 hours).
Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). At least 1 TEAE	5 Participants	5 Participants
Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). At least 1 Serious TEAE	3 Participants	2 Participants
Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). At least 1 Serious TEAE related to Sym004 only	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). At least 1 TEAE leading to Sym004 dose reduction	1 Participants	2 Participants
Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). At least 1 TEAE leading to interruption of Sym004	3 Participants	5 Participants
Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). At least 1 TEAE leading to Sym004 withdrawal	2 Participants	2 Participants
Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). At least 1 TEAE leading to FOLFIRI withdrawal	1 Participants	2 Participants
Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). At least 1 TEAE leading to trial termination	0 Participants	1 Participants
Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). At least 1 TEAE related to Sym004 + FOLFIRI	4 Participants	3 Participants
Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). At least 1 TEAE related to Sym004 only	4 Participants	5 Participants
Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). At least 1 TEAE related to FOLFIRI only	4 Participants	4 Participants
Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). At least 1 TEAE Grade ≥3 related to Sym004+FOLFIRI	2 Participants	2 Participants
Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). At least 1 TEAE Grade ≥ 3 related to Sym004 only	0 Participants	2 Participants
Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). At least 1 TEAE Grade ≥ 3 related to FOLFIRI only	1 Participants	1 Participants
Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). At least 1 dermatologic toxicity	3 Participants	5 Participants
Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). At least 1 TEAE of hypomagnesaemia	3 Participants	0 Participants
Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). At least 1 Infusion related reaction TEAE	3 Participants	3 Participants
Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 4.03) (CTCAE v4.03). At least 1 TEAE resulting in death	0 Participants	0 Participants

Adverse Events

Dose Level 1: Sym004 12 mg/kg + FOLFIRI

Serious events: 3 serious events

Other events: 5 other events

Deaths: 2 deaths

Dose Level -1: Sym004 9 mg/kg + FOLFIRI

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dose Level 1: Sym004 12 mg/kg + FOLFIRI n=5 participants at risk Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR). The standard FOLFIRI regimen consists of Irinotecan (180 mg/m\^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m\^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m\^2 IV bolus, then 2400 mg/m\^2 infused over 46 hours).	Dose Level -1: Sym004 9 mg/kg + FOLFIRI n=5 participants at risk Sym004 is a 1:1 mixture of 2 monoclonal antibodies (mAbs), which bind to 2 non-overlapping epitopes of the epidermal growth factor receptor (EGFR). The standard FOLFIRI regimen consists of Irinotecan (180 mg/m\^2 IV, infused over 60-90 minutes) concurrently with Folinic Acid (400 mg/m\^2 IV, infused over 120 minutes) followed by 5-FU (400 mg/m\^2 IV bolus, then 2400 mg/m\^2 infused over 46 hours).
Gastrointestinal disorders Diarrhoea	40.0% 2/5 • The adverse event data collection period was 15 months. Adverse event data were collected beginning with the signing of informed consent and continued through 1 month (i.e., at least 28 days) after the last administration of treatment (i.e., after both Sym004 and FOLFIRI were discontinued). After the decision was made to prematurely discontinue the trial, collection of adverse event data continued through 1 month after the last administration of Sym004.	0.00% 0/5 • The adverse event data collection period was 15 months. Adverse event data were collected beginning with the signing of informed consent and continued through 1 month (i.e., at least 28 days) after the last administration of treatment (i.e., after both Sym004 and FOLFIRI were discontinued). After the decision was made to prematurely discontinue the trial, collection of adverse event data continued through 1 month after the last administration of Sym004.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/5 • The adverse event data collection period was 15 months. Adverse event data were collected beginning with the signing of informed consent and continued through 1 month (i.e., at least 28 days) after the last administration of treatment (i.e., after both Sym004 and FOLFIRI were discontinued). After the decision was made to prematurely discontinue the trial, collection of adverse event data continued through 1 month after the last administration of Sym004.	20.0% 1/5 • The adverse event data collection period was 15 months. Adverse event data were collected beginning with the signing of informed consent and continued through 1 month (i.e., at least 28 days) after the last administration of treatment (i.e., after both Sym004 and FOLFIRI were discontinued). After the decision was made to prematurely discontinue the trial, collection of adverse event data continued through 1 month after the last administration of Sym004.
Metabolism and nutrition disorders Hyponatraemia	20.0% 1/5 • The adverse event data collection period was 15 months. Adverse event data were collected beginning with the signing of informed consent and continued through 1 month (i.e., at least 28 days) after the last administration of treatment (i.e., after both Sym004 and FOLFIRI were discontinued). After the decision was made to prematurely discontinue the trial, collection of adverse event data continued through 1 month after the last administration of Sym004.	0.00% 0/5 • The adverse event data collection period was 15 months. Adverse event data were collected beginning with the signing of informed consent and continued through 1 month (i.e., at least 28 days) after the last administration of treatment (i.e., after both Sym004 and FOLFIRI were discontinued). After the decision was made to prematurely discontinue the trial, collection of adverse event data continued through 1 month after the last administration of Sym004.
Nervous system disorders Syncope	0.00% 0/5 • The adverse event data collection period was 15 months. Adverse event data were collected beginning with the signing of informed consent and continued through 1 month (i.e., at least 28 days) after the last administration of treatment (i.e., after both Sym004 and FOLFIRI were discontinued). After the decision was made to prematurely discontinue the trial, collection of adverse event data continued through 1 month after the last administration of Sym004.	20.0% 1/5 • The adverse event data collection period was 15 months. Adverse event data were collected beginning with the signing of informed consent and continued through 1 month (i.e., at least 28 days) after the last administration of treatment (i.e., after both Sym004 and FOLFIRI were discontinued). After the decision was made to prematurely discontinue the trial, collection of adverse event data continued through 1 month after the last administration of Sym004.

Other adverse events

Additional Information

Chief Scientific Officer

Symphogen A/S

Phone: +45 8838 2600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Publications shall not disclose any Sponsor confidential information and property (not including the trial results). The Sponsor reserves the right to review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The Sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER