Trial Outcomes & Findings for Sym015 (Anti-MET) in Patients With Advanced Solid Tumor Malignancies (NCT NCT02648724)
NCT ID: NCT02648724
Last Updated: 2022-06-22
Results Overview
The primary objective of Part 1 was to assess the safety and tolerability of Sym015 on a Q2W schedule. This was assessed by evaluating the occurrence of dose-limiting toxicities (DLTs) during Cycle 1 of Sym015 administration. Q2W = every second week.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
57 participants
Primary outcome timeframe
Cycle 1, the initial 28-day period of Q2W dosing
Results posted on
2022-06-22
Participant Flow
Participant milestones
| Measure |
Part 1: Dose-Escalation; Period 1: 6 mg/kg
Patients received 6 mg/kg Symp015.
Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
Patients received 12 mg/kg Symp015.
Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 3:18mg/kg
Patients received 18 mg/kg Symp015.
Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
Patients received 24 mg/kg Symp015-.
Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 2: Dose-Expansion, Basket Cohort
During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:
Basket Cohort:
Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 2: Dose-Expansion, NSCLC MET-Amplified Cohort
During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:
NSCLC MET-Amplified Cohort:
Patients with advanced NSCLC with MET-amplification were to receive Sym015 at the RP2D. Patients may have received prior therapy with METtargeting and/or EGFR-targeting agents.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 2: Dose-Expansion, NSCLC METEx14Del Cohort
During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:
NSCLC METex14del Cohort:
Patients with advanced NSCLC with METex14del were to receive Sym015 at the RP2D. Tumors need not be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents. mutation.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
3
|
3
|
25
|
8
|
12
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
3
|
3
|
25
|
8
|
12
|
Reasons for withdrawal
| Measure |
Part 1: Dose-Escalation; Period 1: 6 mg/kg
Patients received 6 mg/kg Symp015.
Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
Patients received 12 mg/kg Symp015.
Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 3:18mg/kg
Patients received 18 mg/kg Symp015.
Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
Patients received 24 mg/kg Symp015-.
Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 2: Dose-Expansion, Basket Cohort
During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:
Basket Cohort:
Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 2: Dose-Expansion, NSCLC MET-Amplified Cohort
During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:
NSCLC MET-Amplified Cohort:
Patients with advanced NSCLC with MET-amplification were to receive Sym015 at the RP2D. Patients may have received prior therapy with METtargeting and/or EGFR-targeting agents.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 2: Dose-Expansion, NSCLC METEx14Del Cohort
During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:
NSCLC METex14del Cohort:
Patients with advanced NSCLC with METex14del were to receive Sym015 at the RP2D. Tumors need not be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents. mutation.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
1
|
0
|
1
|
0
|
0
|
|
Overall Study
Progressive disease
|
2
|
2
|
2
|
3
|
22
|
7
|
8
|
|
Overall Study
Other reason (unknown)
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
Protocol Violation
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
Death
|
0
|
0
|
0
|
0
|
0
|
0
|
3
|
|
Overall Study
Physician Decision
|
0
|
0
|
0
|
0
|
1
|
0
|
1
|
|
Overall Study
Transferred to named patient program
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
Baseline Characteristics
BMI was not evaluable for all participants
Baseline characteristics by cohort
| Measure |
Part 1: Dose-Escalation, 6 mg/kg
n=3 Participants
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation, 12 mg/kg
n=3 Participants
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation 18 mg/kg
n=3 Participants
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation 24 mg/kg
n=3 Participants
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 2: Dose-Expansion, Basket Cohort
n=25 Participants
Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 2: Dose-Expansion, NSCLC MET-Amplified Cohort
n=8 Participants
Patients with advanced NSCLC with MET-amplification received Sym015 at the RP2D. Patients may have received prior therapy with METtargeting and/or EGFR-targeting agents.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 2: Dose-Expansion, NSCLC METex14del Cohort
n=12 Participants
Patients with advanced NSCLC with METex14del received Sym015 at the RP2D. Tumors need not be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Total
n=57 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
55.7 years
STANDARD_DEVIATION 14.57 • n=5 Participants
|
62.0 years
STANDARD_DEVIATION 11.79 • n=7 Participants
|
55.3 years
STANDARD_DEVIATION 11.24 • n=5 Participants
|
67.3 years
STANDARD_DEVIATION 7.23 • n=4 Participants
|
56.6 years
STANDARD_DEVIATION 11.87 • n=21 Participants
|
65.6 years
STANDARD_DEVIATION 8.91 • n=10 Participants
|
68.5 years
STANDARD_DEVIATION 9.82 • n=115 Participants
|
61.1 years
STANDARD_DEVIATION 11.73 • n=6 Participants
|
|
Age, Customized
18-65 years
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
20 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
6 Participants
n=115 Participants
|
34 Participants
n=6 Participants
|
|
Age, Customized
65 to <75 years
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
5 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
15 Participants
n=6 Participants
|
|
Age, Customized
75 to <85 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
6 Participants
n=115 Participants
|
8 Participants
n=6 Participants
|
|
Age, Customized
85 years or older
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=6 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
5 Participants
n=10 Participants
|
6 Participants
n=115 Participants
|
25 Participants
n=6 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
18 Participants
n=21 Participants
|
3 Participants
n=10 Participants
|
6 Participants
n=115 Participants
|
32 Participants
n=6 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
4 Participants
n=6 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
24 Participants
n=21 Participants
|
8 Participants
n=10 Participants
|
11 Participants
n=115 Participants
|
53 Participants
n=6 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=6 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=6 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
14 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
17 Participants
n=6 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=6 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
2 Participants
n=6 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
6 Participants
n=10 Participants
|
11 Participants
n=115 Participants
|
35 Participants
n=6 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
2 Participants
n=6 Participants
|
|
Region of Enrollment
South Korea
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
12 participants
n=21 Participants
|
2 participants
n=10 Participants
|
0 participants
n=115 Participants
|
14 participants
n=6 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
3 participants
n=4 Participants
|
6 participants
n=21 Participants
|
3 participants
n=10 Participants
|
8 participants
n=115 Participants
|
29 participants
n=6 Participants
|
|
Region of Enrollment
Taiwan
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
1 participants
n=21 Participants
|
0 participants
n=10 Participants
|
0 participants
n=115 Participants
|
1 participants
n=6 Participants
|
|
Region of Enrollment
Denmark
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
0 participants
n=21 Participants
|
1 participants
n=10 Participants
|
1 participants
n=115 Participants
|
2 participants
n=6 Participants
|
|
Region of Enrollment
Spain
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
6 participants
n=21 Participants
|
2 participants
n=10 Participants
|
3 participants
n=115 Participants
|
11 participants
n=6 Participants
|
|
Body weight
|
82.2 kg
STANDARD_DEVIATION 17.86 • n=5 Participants
|
62.5 kg
STANDARD_DEVIATION 12.03 • n=7 Participants
|
89.0 kg
STANDARD_DEVIATION 18.29 • n=5 Participants
|
69.7 kg
STANDARD_DEVIATION 8.05 • n=4 Participants
|
67.1 kg
STANDARD_DEVIATION 10.73 • n=21 Participants
|
60.3 kg
STANDARD_DEVIATION 11.58 • n=10 Participants
|
72.1 kg
STANDARD_DEVIATION 15.54 • n=115 Participants
|
69.1 kg
STANDARD_DEVIATION 13.86 • n=6 Participants
|
|
Body mass index (BMI)
|
28.10 kg per square meter
STANDARD_DEVIATION 1.132 • n=5 Participants • BMI was not evaluable for all participants
|
23.65 kg per square meter
STANDARD_DEVIATION 3.978 • n=7 Participants • BMI was not evaluable for all participants
|
29.84 kg per square meter
STANDARD_DEVIATION 7.452 • n=5 Participants • BMI was not evaluable for all participants
|
25.89 kg per square meter
STANDARD_DEVIATION 5.363 • n=4 Participants • BMI was not evaluable for all participants
|
23.58 kg per square meter
STANDARD_DEVIATION 3.776 • n=21 Participants • BMI was not evaluable for all participants
|
22.15 kg per square meter
STANDARD_DEVIATION 4.590 • n=10 Participants • BMI was not evaluable for all participants
|
25.19 kg per square meter
STANDARD_DEVIATION 4.081 • n=115 Participants • BMI was not evaluable for all participants
|
24.44 kg per square meter
STANDARD_DEVIATION 4.405 • n=6 Participants • BMI was not evaluable for all participants
|
|
ECOG-PS
0
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
11 Participants
n=6 Participants
|
|
ECOG-PS
1
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
21 Participants
n=21 Participants
|
6 Participants
n=10 Participants
|
9 Participants
n=115 Participants
|
44 Participants
n=6 Participants
|
|
ECOG-PS
2
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
2 Participants
n=115 Participants
|
2 Participants
n=6 Participants
|
|
Site of primary tumor
Breast
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
2 Participants
n=6 Participants
|
|
Site of primary tumor
Colon
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
5 Participants
n=6 Participants
|
|
Site of primary tumor
Genitourinary
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
5 Participants
n=6 Participants
|
|
Site of primary tumor
Hepatic (including gallbladder)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Site of primary tumor
Liver
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
3 Participants
n=6 Participants
|
|
Site of primary tumor
Neck
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Site of primary tumor
Other locally advanced sites
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
5 Participants
n=6 Participants
|
|
Site of primary tumor
Other metastatic sites
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
3 Participants
n=6 Participants
|
|
Site of primary tumor
Pancreas
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Site of primary tumor
Respiratory
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
7 Participants
n=10 Participants
|
12 Participants
n=115 Participants
|
19 Participants
n=6 Participants
|
|
Site of primary tumor
Skin/soft tissue
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Site of primary tumor
Gastrointestinal
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
11 Participants
n=6 Participants
|
|
Histopathologic diagnosis
Adenocarcinoma
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
22 Participants
n=21 Participants
|
7 Participants
n=10 Participants
|
11 Participants
n=115 Participants
|
47 Participants
n=6 Participants
|
|
Histopathologic diagnosis
Missing
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
10 Participants
n=6 Participants
|
|
Anatomic based cancer type
Adenocarcinoma of Parotid Gland
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Anatomic based cancer type
Adenocarcinoma of Thymus
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Anatomic based cancer type
BRCA (breast cancer gene)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
2 Participants
n=6 Participants
|
|
Anatomic based cancer type
CRC (colorectal cancer)
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
6 Participants
n=6 Participants
|
|
Anatomic based cancer type
Cholangiocarcinoma
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Anatomic based cancer type
GC (gastric cancer)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
13 Participants
n=6 Participants
|
|
Anatomic based cancer type
GU (genitourinary cancer)
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
5 Participants
n=6 Participants
|
|
Anatomic based cancer type
HCC (hepatocellular carcinoma)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
2 Participants
n=6 Participants
|
|
Anatomic based cancer type
HCC-MIXED
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Anatomic based cancer type
HCC-Neuroendocrine
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Anatomic based cancer type
Lung-Neuroendocrine
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Anatomic based cancer type
NSCLC (non-small-cell lung carcinoma)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
7 Participants
n=10 Participants
|
11 Participants
n=115 Participants
|
18 Participants
n=6 Participants
|
|
Anatomic based cancer type
NSCLC- Sq type
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
2 Participants
n=6 Participants
|
|
Anatomic based cancer type
Nasopharyngeal carcinoma
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Anatomic based cancer type
Pancreatic cancer
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Anatomic based cancer type
SCC (squamous cell carcinoma) of skin/soft tissue
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Time since initial diagnosis
|
4.7 years
STANDARD_DEVIATION 2.52 • n=5 Participants • Data were not available for all patients in Part 2
|
2.3 years
STANDARD_DEVIATION 1.53 • n=7 Participants • Data were not available for all patients in Part 2
|
10.3 years
STANDARD_DEVIATION 9.29 • n=5 Participants • Data were not available for all patients in Part 2
|
2.0 years
STANDARD_DEVIATION 2.0 • n=4 Participants • Data were not available for all patients in Part 2
|
2.1 years
STANDARD_DEVIATION 2.20 • n=21 Participants • Data were not available for all patients in Part 2
|
0 years
STANDARD_DEVIATION 0 • n=10 Participants • Data were not available for all patients in Part 2
|
0 years
STANDARD_DEVIATION 0 • n=115 Participants • Data were not available for all patients in Part 2
|
3.5 years
STANDARD_DEVIATION 4.57 • n=6 Participants • Data were not available for all patients in Part 2
|
|
Previous debulking surgery
No
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
16 Participants
n=21 Participants
|
7 Participants
n=10 Participants
|
12 Participants
n=115 Participants
|
44 Participants
n=6 Participants
|
|
Previous debulking surgery
Yes
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
13 Participants
n=6 Participants
|
|
Sites with metastasis
Abdomen, pelvis
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Sites with metastasis
Abdominal cavity, diaphragm, subcutis, para- renal mass, Sub-Hepatic Mass
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Sites with metastasis
Adrenal gland
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
4 Participants
n=115 Participants
|
10 Participants
n=6 Participants
|
|
Sites with metastasis
Bone
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
7 Participants
n=115 Participants
|
20 Participants
n=6 Participants
|
|
Sites with metastasis
Both ovaries, peritoneum, colon
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Sites with metastasis
Brain
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
5 Participants
n=6 Participants
|
|
Sites with metastasis
Duodenum
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Sites with metastasis
Effusion
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Sites with metastasis
Kidney
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
2 Participants
n=115 Participants
|
2 Participants
n=6 Participants
|
|
Sites with metastasis
Liver
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
2 Participants
n=115 Participants
|
17 Participants
n=6 Participants
|
|
Sites with metastasis
Lungs
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
7 Participants
n=10 Participants
|
9 Participants
n=115 Participants
|
31 Participants
n=6 Participants
|
|
Sites with metastasis
Lymph nodes
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
20 Participants
n=21 Participants
|
6 Participants
n=10 Participants
|
7 Participants
n=115 Participants
|
41 Participants
n=6 Participants
|
|
Sites with metastasis
Lymph nodes and Lymphangitis Carcinomatoses
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Sites with metastasis
Muscle
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Sites with metastasis
Pelvis, abdominal wall, spleen
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Sites with metastasis
Peritoneal
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
2 Participants
n=6 Participants
|
|
Sites with metastasis
Peritoneum, peribiliary
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Sites with metastasis
Pleura
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
2 Participants
n=115 Participants
|
2 Participants
n=6 Participants
|
|
Sites with metastasis
Pleural based metastases
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Sites with metastasis
Primary gastric cancer
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Sites with metastasis
Rectum
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Sites with metastasis
Skin
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
2 Participants
n=6 Participants
|
|
Sites with metastasis
Soft tissue
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
3 Participants
n=115 Participants
|
8 Participants
n=6 Participants
|
|
Sites with metastasis
Spleen, pelvis, abdomen, left ovary
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Sites with metastasis
Subpleura
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Sites with metastasis
Thyroid gland
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=6 Participants
|
|
Number of sites with metastasis
0
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=6 Participants
|
|
Number of sites with metastasis
1
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
12 Participants
n=6 Participants
|
|
Number of sites with metastasis
2
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
3 Participants
n=115 Participants
|
13 Participants
n=6 Participants
|
|
Number of sites with metastasis
3
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
3 Participants
n=10 Participants
|
4 Participants
n=115 Participants
|
17 Participants
n=6 Participants
|
|
Number of sites with metastasis
More than 3
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
4 Participants
n=115 Participants
|
15 Participants
n=6 Participants
|
PRIMARY outcome
Timeframe: Cycle 1, the initial 28-day period of Q2W dosingPopulation: For evaluation of DLTs, the DLT analysis set was used. This comprised all patients enrolled in Part 1 who had received at least one dose of Sym015, except patients who did not complete Cycle 1 (i.e., the initial 28-day period of Q2W dosing) for reasons other than drug toxicity.
The primary objective of Part 1 was to assess the safety and tolerability of Sym015 on a Q2W schedule. This was assessed by evaluating the occurrence of dose-limiting toxicities (DLTs) during Cycle 1 of Sym015 administration. Q2W = every second week.
Outcome measures
| Measure |
Part 1: Dose-Escalation; Period 1, 6 mg/kg
n=3 Participants
Patients received 6 mg/kg Sym015.
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
n=3 Participants
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET
|
Part 1: Dose-Escalation; Period 3:18mg/kg
n=3 Participants
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
n=3 Participants
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|
|
Part 1: Occurrence of DLTs During Cycle 1 of Sym015 Administration
|
0 Number of DLTs
|
0 Number of DLTs
|
0 Number of DLTs
|
0 Number of DLTs
|
PRIMARY outcome
Timeframe: 24 monthsPopulation: The Full Analysis Set (FAS) comprised all enrolled patients who had received at least one dose of Sym015.
The primary objective of Part 2 was to evaluate the antitumor activity of Sym015 when administered at the Q2W RP2D to patients in the different cohorts. Documented OR was defined as partial response \[PR\] or complete response \[CR\]) as assessed by CT or MRI using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at any time during trial participation by Investigator assessment. PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; CR = Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). Q2W = every second week. RP2D = recommended phase 2 dose.
Outcome measures
| Measure |
Part 1: Dose-Escalation; Period 1, 6 mg/kg
n=25 Participants
Patients received 6 mg/kg Sym015.
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
n=8 Participants
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET
|
Part 1: Dose-Escalation; Period 3:18mg/kg
n=12 Participants
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|
|
Part 2: Documented, Confirmed Objective Response (OR)
|
0 Participants
|
2 Participants
|
3 Participants
|
—
|
SECONDARY outcome
Timeframe: 12 MonthsPopulation: It was not possible to determine this endpoint as no DLTs were observed. The RP2D combination was not established and was instead chosen based on other safety findings as well as pharmacokinetic data, as described in the protocol.
Determination based on an evaluation of the patient data for DLTs from Part 1. Q2W = every second week. RP2D = recommended phase 2 dose.
Outcome measures
| Measure |
Part 1: Dose-Escalation; Period 1, 6 mg/kg
n=12 Participants
Patients received 6 mg/kg Sym015.
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET
|
Part 1: Dose-Escalation; Period 3:18mg/kg
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|
|
Part 1: Determine a Q2W RP2D of Sym015.
|
NA mg/kg
RP2D was not established as no DLTs were observed.
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day (D) 1, Cycle 3, 5, 7: D1 (+-2), End of treatment: At or by D10, Follow-up: 1 month after last dose of study treatment (30+7D)Population: The Full Analysis Set (FAS) comprised all enrolled patients who had received at least one dose of Sym015.
Serum sampling was done to assess the potential for anti-drug antibody (ADA) formation.
Outcome measures
| Measure |
Part 1: Dose-Escalation; Period 1, 6 mg/kg
n=3 Participants
Patients received 6 mg/kg Sym015.
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
n=3 Participants
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET
|
Part 1: Dose-Escalation; Period 3:18mg/kg
n=3 Participants
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
n=3 Participants
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|
|
Immunogenicity of Sym015: Part 1.
Cycle 1 - day 1 · Not done
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Immunogenicity of Sym015: Part 1.
Cycle 1 - day 1 · Negative
|
3 Participants
|
3 Participants
|
3 Participants
|
3 Participants
|
|
Immunogenicity of Sym015: Part 1.
Cycle 1 - day 1 · Patient withdrawn
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Immunogenicity of Sym015: Part 1.
Cycle 3 - day 1 · Not done
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Immunogenicity of Sym015: Part 1.
Cycle 3 - day 1 · Negative
|
1 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
|
Immunogenicity of Sym015: Part 1.
Cycle 3 - day 1 · Patient withdrawn
|
2 Participants
|
3 Participants
|
1 Participants
|
3 Participants
|
|
Immunogenicity of Sym015: Part 1.
End of treatment · Not done
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Immunogenicity of Sym015: Part 1.
End of treatment · Negative
|
3 Participants
|
2 Participants
|
1 Participants
|
2 Participants
|
|
Immunogenicity of Sym015: Part 1.
End of treatment · Patient withdrawn
|
0 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
|
Immunogenicity of Sym015: Part 1.
1-month follow-up · Not done
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Immunogenicity of Sym015: Part 1.
1-month follow-up · Negative
|
2 Participants
|
1 Participants
|
0 Participants
|
2 Participants
|
|
Immunogenicity of Sym015: Part 1.
1-month follow-up · Patient withdrawn
|
1 Participants
|
1 Participants
|
3 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Cycle 1: Day (D) 1, Cycle 2, 3, 5, 7: D1 (+-2), End of treatment: At or by D10, Follow-up: 1 month after last dose of study treatment (30+7D)Population: The Full Analysis Set (FAS) comprised all enrolled patients who had received at least one dose of Sym015.
Serum sampling was done to assess the potential for anti-drug antibody (ADA) formation.
Outcome measures
| Measure |
Part 1: Dose-Escalation; Period 1, 6 mg/kg
n=25 Participants
Patients received 6 mg/kg Sym015.
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
n=8 Participants
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET
|
Part 1: Dose-Escalation; Period 3:18mg/kg
n=12 Participants
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|
|
Immunogenicity of Sym015: Part 2.
Cycle 1 - day 1 · Not done
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
Cycle 1 - day 1 · Negative
|
25 Participants
|
8 Participants
|
12 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
Cycle 1 - day 1 · Positive
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
Cycle 1 - day 1 · Patient withdrawn
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
Cycle 2 - day 1 · Not done
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
Cycle 2 - day 1 · Negative
|
21 Participants
|
8 Participants
|
11 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
Cycle 2 - day 1 · Positive
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
Cycle 2 - day 1 · Patient withdrawn
|
3 Participants
|
0 Participants
|
1 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
Cycle 3 - day 1 · Not done
|
1 Participants
|
1 Participants
|
0 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
Cycle 3 - day 1 · Negative
|
8 Participants
|
7 Participants
|
8 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
Cycle 3 - day 1 · Positive
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
Cycle 3 - day 1 · Patient withdrawn
|
16 Participants
|
0 Participants
|
4 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
Cycle 5 - day 1 · Not done
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
Cycle 5 - day 1 · Negative
|
6 Participants
|
6 Participants
|
5 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
Cycle 5 - day 1 · Positive
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
Cycle 5 - day 1 · Patient withdrawn
|
19 Participants
|
2 Participants
|
6 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
Cycle 7 - day 1 · Not done
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
Cycle 7 - day 1 · Negative
|
2 Participants
|
2 Participants
|
5 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
Cycle 7 - day 1 · Positive
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
Cycle 7 - day 1 · Patient withdrawn
|
23 Participants
|
5 Participants
|
7 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
End of treatment · Not done
|
5 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
End of treatment · Negative
|
15 Participants
|
7 Participants
|
9 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
End of treatment · Positive
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
End of treatment · Patient withdrawn
|
4 Participants
|
1 Participants
|
3 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
1-month follow up · Not done
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
1-month follow up · Negative
|
10 Participants
|
3 Participants
|
5 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
1-month follow up · Positive
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Immunogenicity of Sym015: Part 2.
1-month follow up · Patient withdrawn
|
14 Participants
|
4 Participants
|
6 Participants
|
—
|
SECONDARY outcome
Timeframe: From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.Estimated using non-compartmental methods and actual time points following the first dose of Sym015.
Outcome measures
| Measure |
Part 1: Dose-Escalation; Period 1, 6 mg/kg
n=3 Participants
Patients received 6 mg/kg Sym015.
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
n=3 Participants
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET
|
Part 1: Dose-Escalation; Period 3:18mg/kg
n=3 Participants
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
n=3 Participants
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|
|
Part 1: Area Under the Concentration-time Curve in a Dosing Interval (AUC) Following 1st Dose
|
17900 h*μg/mL
Interval 17100.0 to 24500.0
|
35700 h*μg/mL
Interval 31600.0 to 42900.0
|
82500 h*μg/mL
Interval 75200.0 to 86200.0
|
76800 h*μg/mL
Interval 55200.0 to 86400.0
|
SECONDARY outcome
Timeframe: From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.Estimated using non-compartmental methods and actual time points following the first dose of Sym015 for the whole basket cohort.
Outcome measures
| Measure |
Part 1: Dose-Escalation; Period 1, 6 mg/kg
n=25 Participants
Patients received 6 mg/kg Sym015.
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
n=8 Participants
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET
|
Part 1: Dose-Escalation; Period 3:18mg/kg
n=12 Participants
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|
|
Part 2: Area Under the Concentration-time Curve in a Dosing Interval (AUC)
|
34000 h*ug/mL
Interval 17300.0 to 51800.0
|
37200 h*ug/mL
Interval 22000.0 to 55000.0
|
38700 h*ug/mL
Interval 11300.0 to 54000.0
|
—
|
SECONDARY outcome
Timeframe: From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.Maximum serum concentration was derived from observed data.
Outcome measures
| Measure |
Part 1: Dose-Escalation; Period 1, 6 mg/kg
n=3 Participants
Patients received 6 mg/kg Sym015.
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
n=3 Participants
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET
|
Part 1: Dose-Escalation; Period 3:18mg/kg
n=3 Participants
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
n=3 Participants
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|
|
Part 1: Cmax
|
146 ug/mL
Interval 141.0 to 151.0
|
286 ug/mL
Interval 275.0 to 323.0
|
563 ug/mL
Interval 419.0 to 711.0
|
561 ug/mL
Interval 379.0 to 726.0
|
SECONDARY outcome
Timeframe: From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.Maximum serum concentration was derived from observed data following the first dose of Sym015 for the full basket cohort.
Outcome measures
| Measure |
Part 1: Dose-Escalation; Period 1, 6 mg/kg
n=25 Participants
Patients received 6 mg/kg Sym015.
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
n=8 Participants
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET
|
Part 1: Dose-Escalation; Period 3:18mg/kg
n=12 Participants
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|
|
Part 2: Cmax
|
420 ug/mL
Interval 310.0 to 700.0
|
520 ug/mL
Interval 320.0 to 610.0
|
510 ug/mL
Interval 330.0 to 1180.0
|
—
|
SECONDARY outcome
Timeframe: From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.Time to reach maximum concentration (Tmax) was derived from observed data.
Outcome measures
| Measure |
Part 1: Dose-Escalation; Period 1, 6 mg/kg
n=3 Participants
Patients received 6 mg/kg Sym015.
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
n=3 Participants
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET
|
Part 1: Dose-Escalation; Period 3:18mg/kg
n=3 Participants
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
n=3 Participants
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|
|
Part 1: Time to Reach Maximum Concentration (Tmax)
|
2.1 hours
Interval 2.0 to 5.0
|
1.1 hours
Interval 1.0 to 2.0
|
3.5 hours
Interval 3.0 to 4.0
|
3.0 hours
Interval 3.0 to 9.0
|
SECONDARY outcome
Timeframe: From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.Time to reach maximum concentration (Tmax) was derived from observed data following the first dose of Sym015 for the full basket cohort.
Outcome measures
| Measure |
Part 1: Dose-Escalation; Period 1, 6 mg/kg
n=25 Participants
Patients received 6 mg/kg Sym015.
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
n=8 Participants
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET
|
Part 1: Dose-Escalation; Period 3:18mg/kg
n=12 Participants
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|
|
Part 2: Time to Reach Maximum Concentration (Tmax)
|
2.5 hours
Interval 1.0 to 44.0
|
3.7 hours
Interval 2.0 to 8.0
|
2.8 hours
Interval 2.0 to 7.0
|
—
|
SECONDARY outcome
Timeframe: From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.Ctrough was derived from observed data.
Outcome measures
| Measure |
Part 1: Dose-Escalation; Period 1, 6 mg/kg
n=3 Participants
Patients received 6 mg/kg Sym015.
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
n=3 Participants
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET
|
Part 1: Dose-Escalation; Period 3:18mg/kg
n=3 Participants
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
n=3 Participants
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|
|
Part 1: Trough Concentration (Ctrough)
|
23.1 μg/mL
Interval 19.2 to 31.5
|
61.3 μg/mL
Interval 56.1 to 65.0
|
130 μg/mL
Interval 127.0 to 187.0
|
92.4 μg/mL
Interval 91.3 to 151.0
|
SECONDARY outcome
Timeframe: From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.Ctrough was derived from observed data following the first dose of Sym015 for the whole basket cohort.
Outcome measures
| Measure |
Part 1: Dose-Escalation; Period 1, 6 mg/kg
n=24 Participants
Patients received 6 mg/kg Sym015.
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
n=8 Participants
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET
|
Part 1: Dose-Escalation; Period 3:18mg/kg
n=11 Participants
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|
|
Part 2: Trough Concentration (Ctrough)
|
84.1 μg/mL
Interval 24.0 to 429.0
|
90.1 μg/mL
Interval 51.0 to 183.0
|
101.7 μg/mL
Interval 66.0 to 250.0
|
—
|
SECONDARY outcome
Timeframe: From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.Population: Numbers reflects evaluable participants. Evaluable participants = T½ is only reported if at least three data points were available in the terminal phase, R2 in 0.85 or above and the time span between the first and the last data point for z covers at least 1.5 half-lives. Reference: V-QUAL-107812
Estimated using non-compartmental methods and actual time points.
Outcome measures
| Measure |
Part 1: Dose-Escalation; Period 1, 6 mg/kg
n=3 Participants
Patients received 6 mg/kg Sym015.
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
n=1 Participants
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET
|
Part 1: Dose-Escalation; Period 3:18mg/kg
n=1 Participants
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
n=1 Participants
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|
|
Part 1: Elimination Half-life (T½)
|
179 hours
Interval 116.0 to 179.0
|
137 hours
Interval 137.0 to 137.0
|
193 hours
Interval 193.0 to 193.0
|
170 hours
Interval 170.0 to 170.0
|
SECONDARY outcome
Timeframe: From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.Estimated using non-compartmental methods and actual time points following the first dose of Sym015 for the whole basket cohort.
Outcome measures
| Measure |
Part 1: Dose-Escalation; Period 1, 6 mg/kg
n=13 Participants
Patients received 6 mg/kg Sym015.
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
n=6 Participants
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET
|
Part 1: Dose-Escalation; Period 3:18mg/kg
n=7 Participants
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|
|
Part 2: Elimination Half-life (T½)
|
150 hours
Interval 87.0 to 217.0
|
191 hours
Interval 103.0 to 208.0
|
171 hours
Interval 116.0 to 204.0
|
—
|
SECONDARY outcome
Timeframe: From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.Population: Samples were determined for subjects in the 6 and 12 mg/kg cohorts. No samples from subjects in the 18 and 24 mg/kg cohorts were available for analysis.
Estimated using non-compartmental methods and actual time points.
Outcome measures
| Measure |
Part 1: Dose-Escalation; Period 1, 6 mg/kg
n=1 Participants
Patients received 6 mg/kg Sym015.
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
n=1 Participants
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET
|
Part 1: Dose-Escalation; Period 3:18mg/kg
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|
|
Part 1: Clearance (CL)
|
0.3 mL/h
Interval 0.3 to 0.3
|
0.2 mL/h
Interval 0.2 to 0.2
|
—
|
—
|
SECONDARY outcome
Timeframe: From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.Estimated using non-compartmental methods and actual time points following the first dose of Sym015 for the whole basket cohort.
Outcome measures
| Measure |
Part 1: Dose-Escalation; Period 1, 6 mg/kg
n=7 Participants
Patients received 6 mg/kg Sym015.
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
n=1 Participants
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET
|
Part 1: Dose-Escalation; Period 3:18mg/kg
n=2 Participants
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|
|
Part 2: Clearance (CL)
|
0.4 mL/h/kg
Interval 0.2 to 0.5
|
0.2 mL/h/kg
Interval 0.2 to 0.2
|
0.2 mL/h/kg
Interval 0.2 to 0.2
|
—
|
SECONDARY outcome
Timeframe: 24 MonthsThis applies to the subset of patients in the Basket Cohort who received prior therapy with a MET-targeting TKI. Documented OR (defined as PR or CR), assessed by RECIST v1.1 at any time during trial participation by Investigator assessment. Objective Response (OR) is presented. Documented OR was defined as partial response \[PR\] or complete response \[CR\]) as assessed by CT or MRI using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at any time during trial participation by Investigator assessment. PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; CR = Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis).
Outcome measures
| Measure |
Part 1: Dose-Escalation; Period 1, 6 mg/kg
n=5 Participants
Patients received 6 mg/kg Sym015.
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
n=20 Participants
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET
|
Part 1: Dose-Escalation; Period 3:18mg/kg
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|
|
Part 2: Additional Preliminary Evaluation of the Antitumor Activity of Sym015 When Administered at the Q2W RP2D in a Subset of Patients. Assessed by OR.
|
0 Participants
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 24 MonthsThis applies to the subset of patients in the Basket Cohort who received prior therapy with a MET-targeting TKI. Documented OR (defined as PR or CR), assessed by RECIST v1.1 at any time during trial participation by Investigator assessment. Disease control rate (DCR) is presented. The DCR was defined as the percentage of patients who had BOR of confirmed CR or confirmed PR or SD (including unconfirmed CR/PR, provided 6 weeks minimum criteria for SD duration was met). BOR = Best Overall Response. CR = Complete Response. PR = Partial Response. SD = Stable Disease.
Outcome measures
| Measure |
Part 1: Dose-Escalation; Period 1, 6 mg/kg
n=5 Participants
Patients received 6 mg/kg Sym015.
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
n=20 Participants
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET
|
Part 1: Dose-Escalation; Period 3:18mg/kg
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|
|
Part 2: Additional Preliminary Evaluation of the Antitumor Activity of Sym015 When Administered at the Q2W RP2D in a Subset of Patients. Assessed by DCR.
|
2 Participants
|
8 Participants
|
—
|
—
|
Adverse Events
Part 1: Dose-Escalation; Period 1: 6 mg/kg
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Part 1: Dose-Escalation; Period 2: 12mg/kg
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Part 1: Dose-Escalation; Period 3:18mg/kg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Part 1: Dose-Escalation; Period 4: 24 mg/kg
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Part 2: Dose-Expansion, Basket Cohort
Serious events: 8 serious events
Other events: 23 other events
Deaths: 0 deaths
Part 2: Dose-Expansion, NSCLC MET-Amplified Cohort
Serious events: 4 serious events
Other events: 8 other events
Deaths: 0 deaths
Part 2: Dose-Expansion, NSCLC METEx14Del Cohort
Serious events: 6 serious events
Other events: 12 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Part 1: Dose-Escalation; Period 1: 6 mg/kg
n=3 participants at risk
Patients received 6 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
n=3 participants at risk
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 3:18mg/kg
n=3 participants at risk
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
n=3 participants at risk
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 2: Dose-Expansion, Basket Cohort
n=25 participants at risk
During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:
Basket Cohort:
Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 2: Dose-Expansion, NSCLC MET-Amplified Cohort
n=8 participants at risk
During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:
NSCLC MET-Amplified Cohort:
Patients with advanced NSCLC with MET-amplification were to receive Sym015 at the RP2D. Patients may have received prior therapy with METtargeting and/or EGFR-targeting agents.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 2: Dose-Expansion, NSCLC METEx14Del Cohort
n=12 participants at risk
During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:
NSCLC METex14del Cohort:
Patients with advanced NSCLC with METex14del were to receive Sym015 at the RP2D. Tumors need not be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents. mutation.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|---|---|---|
|
Infections and infestations
Pelvic abscess
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Gastrointestinal disorders
Intra-abdominal fluid collection
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
4.0%
1/25 • Number of events 1 • 24 months
|
0.00%
0/8 • 24 months
|
8.3%
1/12 • Number of events 2 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
8.3%
1/12 • Number of events 3 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
8.3%
1/12 • Number of events 2 • 24 months
|
|
Infections and infestations
Pneumonia
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
12.5%
1/8 • Number of events 1 • 24 months
|
8.3%
1/12 • Number of events 1 • 24 months
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Infections and infestations
Bone abscess
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
4.0%
1/25 • Number of events 1 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Infections and infestations
Infection
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
12.5%
1/8 • Number of events 1 • 24 months
|
0.00%
0/12 • 24 months
|
|
Infections and infestations
Septic shock
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
12.5%
1/8 • Number of events 1 • 24 months
|
0.00%
0/12 • 24 months
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
4.0%
1/25 • Number of events 1 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
4.0%
1/25 • Number of events 1 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
4.0%
1/25 • Number of events 1 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Gastrointestinal disorders
Small intestinal perforation
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
8.3%
1/12 • Number of events 1 • 24 months
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
4.0%
1/25 • Number of events 2 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
4.0%
1/25 • Number of events 1 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
General disorders
Generalized edema
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
4.0%
1/25 • Number of events 1 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
General disorders
Edema peripheral
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
12.5%
1/8 • Number of events 1 • 24 months
|
0.00%
0/12 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
8.3%
1/12 • Number of events 1 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
4.0%
1/25 • Number of events 1 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
4.0%
1/25 • Number of events 1 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Hepatobiliary disorders
Hepatitis
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
12.5%
1/8 • Number of events 1 • 24 months
|
0.00%
0/12 • 24 months
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
8.3%
1/12 • Number of events 1 • 24 months
|
|
Vascular disorders
Peripheral ischemia
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
12.5%
1/8 • Number of events 1 • 24 months
|
0.00%
0/12 • 24 months
|
Other adverse events
| Measure |
Part 1: Dose-Escalation; Period 1: 6 mg/kg
n=3 participants at risk
Patients received 6 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 2: 12mg/kg
n=3 participants at risk
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 3:18mg/kg
n=3 participants at risk
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 1: Dose-Escalation; Period 4: 24 mg/kg
n=3 participants at risk
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 2: Dose-Expansion, Basket Cohort
n=25 participants at risk
During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:
Basket Cohort:
Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 2: Dose-Expansion, NSCLC MET-Amplified Cohort
n=8 participants at risk
During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:
NSCLC MET-Amplified Cohort:
Patients with advanced NSCLC with MET-amplification were to receive Sym015 at the RP2D. Patients may have received prior therapy with METtargeting and/or EGFR-targeting agents.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
Part 2: Dose-Expansion, NSCLC METEx14Del Cohort
n=12 participants at risk
During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:
NSCLC METex14del Cohort:
Patients with advanced NSCLC with METex14del were to receive Sym015 at the RP2D. Tumors need not be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents. mutation.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
|
|---|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
24.0%
6/25 • Number of events 6 • 24 months
|
25.0%
2/8 • Number of events 2 • 24 months
|
16.7%
2/12 • Number of events 2 • 24 months
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
20.0%
5/25 • Number of events 5 • 24 months
|
25.0%
2/8 • Number of events 2 • 24 months
|
16.7%
2/12 • Number of events 2 • 24 months
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
20.0%
5/25 • Number of events 5 • 24 months
|
12.5%
1/8 • Number of events 2 • 24 months
|
8.3%
1/12 • Number of events 1 • 24 months
|
|
Gastrointestinal disorders
Dyspepsia
|
33.3%
1/3 • Number of events 2 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
8.0%
2/25 • Number of events 2 • 24 months
|
25.0%
2/8 • Number of events 2 • 24 months
|
8.3%
1/12 • Number of events 2 • 24 months
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
1/3 • Number of events 1 • 24 months
|
33.3%
1/3 • Number of events 2 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
8.0%
2/25 • Number of events 2 • 24 months
|
25.0%
2/8 • Number of events 2 • 24 months
|
0.00%
0/12 • 24 months
|
|
Gastrointestinal disorders
Diarrhea
|
33.3%
1/3 • Number of events 2 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
8.0%
2/25 • Number of events 2 • 24 months
|
0.00%
0/8 • 24 months
|
16.7%
2/12 • Number of events 2 • 24 months
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
8.0%
2/25 • Number of events 2 • 24 months
|
12.5%
1/8 • Number of events 1 • 24 months
|
0.00%
0/12 • 24 months
|
|
Gastrointestinal disorders
Presbyesophagus
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Gastrointestinal disorders
Salivary gland enlargement
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
General disorders
Edema peripheral
|
33.3%
1/3 • Number of events 1 • 24 months
|
33.3%
1/3 • Number of events 3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
4.0%
1/25 • Number of events 1 • 24 months
|
37.5%
3/8 • Number of events 6 • 24 months
|
58.3%
7/12 • Number of events 11 • 24 months
|
|
General disorders
Fatigue
|
33.3%
1/3 • Number of events 1 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
24.0%
6/25 • Number of events 7 • 24 months
|
12.5%
1/8 • Number of events 1 • 24 months
|
25.0%
3/12 • Number of events 3 • 24 months
|
|
General disorders
Pyrexia
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
16.0%
4/25 • Number of events 8 • 24 months
|
25.0%
2/8 • Number of events 2 • 24 months
|
8.3%
1/12 • Number of events 1 • 24 months
|
|
General disorders
Asthenia
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
8.0%
2/25 • Number of events 2 • 24 months
|
12.5%
1/8 • Number of events 1 • 24 months
|
8.3%
1/12 • Number of events 1 • 24 months
|
|
General disorders
Early satiety
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
General disorders
Facial pain
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
General disorders
Feeling abnormal
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
General disorders
Pain
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Metabolism and nutrition disorders
Decreased appetite
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
24.0%
6/25 • Number of events 6 • 24 months
|
0.00%
0/8 • 24 months
|
25.0%
3/12 • Number of events 4 • 24 months
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
33.3%
1/3 • Number of events 1 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
20.0%
5/25 • Number of events 7 • 24 months
|
12.5%
1/8 • Number of events 1 • 24 months
|
8.3%
1/12 • Number of events 2 • 24 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
66.7%
2/3 • Number of events 2 • 24 months
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
8.0%
2/25 • Number of events 6 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
12.0%
3/25 • Number of events 5 • 24 months
|
0.00%
0/8 • 24 months
|
8.3%
1/12 • Number of events 1 • 24 months
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
4.0%
1/25 • Number of events 1 • 24 months
|
37.5%
3/8 • Number of events 3 • 24 months
|
8.3%
1/12 • Number of events 1 • 24 months
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
16.0%
4/25 • Number of events 5 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
8.0%
2/25 • Number of events 2 • 24 months
|
25.0%
2/8 • Number of events 2 • 24 months
|
0.00%
0/12 • 24 months
|
|
Investigations
Weight decreased
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
4.0%
1/25 • Number of events 1 • 24 months
|
12.5%
1/8 • Number of events 2 • 24 months
|
0.00%
0/12 • 24 months
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
8.0%
2/25 • Number of events 2 • 24 months
|
12.5%
1/8 • Number of events 1 • 24 months
|
0.00%
0/12 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
8.0%
2/25 • Number of events 4 • 24 months
|
12.5%
1/8 • Number of events 1 • 24 months
|
41.7%
5/12 • Number of events 6 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
4.0%
1/25 • Number of events 1 • 24 months
|
12.5%
1/8 • Number of events 1 • 24 months
|
16.7%
2/12 • Number of events 3 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
8.0%
2/25 • Number of events 2 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Nervous system disorders
Headache
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
37.5%
3/8 • Number of events 3 • 24 months
|
0.00%
0/12 • 24 months
|
|
Nervous system disorders
Somnolence
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
25.0%
2/8 • Number of events 2 • 24 months
|
0.00%
0/12 • 24 months
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
4.0%
1/25 • Number of events 1 • 24 months
|
0.00%
0/8 • 24 months
|
16.7%
2/12 • Number of events 2 • 24 months
|
|
Nervous system disorders
Dizziness
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Nervous system disorders
Cognitive disorder
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
24.0%
6/25 • Number of events 9 • 24 months
|
12.5%
1/8 • Number of events 1 • 24 months
|
8.3%
1/12 • Number of events 3 • 24 months
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
4.0%
1/25 • Number of events 1 • 24 months
|
12.5%
1/8 • Number of events 1 • 24 months
|
8.3%
1/12 • Number of events 1 • 24 months
|
|
Infections and infestations
Cystitis
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
12.0%
3/25 • Number of events 3 • 24 months
|
37.5%
3/8 • Number of events 3 • 24 months
|
0.00%
0/12 • 24 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
8.0%
2/25 • Number of events 2 • 24 months
|
12.5%
1/8 • Number of events 2 • 24 months
|
0.00%
0/12 • 24 months
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/3 • 24 months
|
66.7%
2/3 • Number of events 3 • 24 months
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Ear and labyrinth disorders
Ear discomfort
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Ear and labyrinth disorders
Ear hemorrhage
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
66.7%
2/3 • Number of events 2 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain
|
33.3%
1/3 • Number of events 1 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Vascular disorders
Flushing
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Vascular disorders
Hypertension
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
|
Reproductive system and breast disorders
Pelvic discomfort
|
0.00%
0/3 • 24 months
|
33.3%
1/3 • Number of events 1 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/3 • 24 months
|
0.00%
0/25 • 24 months
|
0.00%
0/8 • 24 months
|
0.00%
0/12 • 24 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place