MET Gene Amplification, MET Gene Mutation, Non Small Cell Lung Cancer, NSCLC, Oncology
Conditions
Keywords
Advanced Solid Tumor Malignancies, MET Gene Amplification, MET Amplification, Wild-type, NSCLC, METex14del, Non-Small Cell Lung Carcinoma
Brief summary
This is the first study to test Sym015 in humans. The primary purpose of this study is to see if Sym015 is safe and effective for patients with advanced solid tumor malignancies without available therapeutic options.
Detailed description
In the first part of the study (Part 1, dose-escalation), Sym015 was evaluated for safety and tolerability. Additionally, the recommended Phase 2 dose (RP2D) was to be determined. Sym015 was given at different dose levels on an every second week (Q2W) dosing schedule. Each patient was given one single weight based dose level. In the second part of the study (Part 2, dose-expansion), dosing was to be at the RP2D on a Q2W dosing schedule. Three cohorts were included: * Basket Cohort: Patients with KRAS wild-type (WT) advanced solid tumor malignancies with MET-amplification and without therapeutic options. Patients must have no prior therapy with MET-targeting agents, except a subset of patients having received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI). As of December 2018, accrual to this cohort was suspended. * Non-Small Cell Lung Carcinoma (NSCLC) MET-Amplified Cohort: Patients with advanced NSCLC with MET-amplification, and without available therapeutic options. Patients may have received prior therapy with MET-targeting and/or epidermal growth factor receptor (EGFR)-targeting agents. * NSCLC with MET exon 14 skipping alteration (METex14del) Cohort: Patients with advanced NSCLC METex14del, and without therapeutic options. Tumors need not be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.
Interventions
DRUGSym015
Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
Sponsors
Symphogen A/S
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Arms 1-4 comprises part 1 (dose-escalation), which is an as evaluation of 4 different dose levels (DL), 6, 12, 18, and 24 mg/kg. DL data from part 1 is presented as merged in the other sections. This is due to that there were no dose level toxicities reported during the study. Arms 5-7 comprises part 2 (dose-expansion).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. * Life expectancy \>3 months assessed during Screening. * Documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic, and that is refractory to standard therapy or for which no standard therapy is available or accessible. * If female and of childbearing potential: a negative pregnancy test. * Male or female: either not of childbearing potential or agreeing to use a medically effective method of contraception as per institutional standards during the trial and for 4 months after the last dose of trial drug. * Part 1 ONLY: Tumor documented to be KRAS WT by local assessment. * Part 2 ONLY: * Measurable disease according to RECIST v1.1 that has been confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) within 4 weeks prior to Cycle 1/Day 1 (C1/D1). * Basket Cohort ONLY: * Tumor documented to be KRAS WT by local assessment according to institutional standards. If KRAS WT is not previously documented and if archival tissue is not available for pretrial assessment, patient must be willing to undergo a tumor biopsy to confirm eligibility. * Confirmed MET-amplification by local assessment. * No prior therapy with MET-targeting agents (except a subset of patients having received prior therapy with a MET-targeting TKI). * Willingness to undergo a pre- and post-dosing biopsy (maximum of 2 biopsies) from primary or metastatic tumor site(s) considered safely accessible for biopsy * NSCLC MET-Amplified Cohort ONLY: * Documented NSCLC meeting disease criteria as defined per protocol. * Documented MET-amplification. * May have received prior therapy with MET-targeting and/or EGFR-targeting agents (antibodies or TKIs). * Willingness to undergo a pre-dosing biopsy (mandatory unless a recent tumor biopsy is available), and potentially a biopsy at the End of Cycle 2 (EOC2) (optional), from a primary or metastatic tumor site considered safely accessible for biopsy. * NSCLC METex14del Cohort ONLY: * Documented NSCLC meeting disease criteria as defined per protocol. * Documented METex14del (tumors need not be MET-amplified). * May have received prior therapy with MET-targeting and/or EGFR-targeting agents (antibodies or TKIs). * Willingness to undergo a pre-dosing biopsy (mandatory unless a recent tumor biopsy is available), and potentially a biopsy at the EOC2 (optional), from a primary or metastatic tumor site considered safely accessible for biopsy.
Exclusion criteria
* Any antineoplastic agent for the primary malignancy (standard or investigational) without delayed toxicity within 4 weeks or 5 plasma half-lives, whichever is shortest, prior to C1/D1, except nitrosoureas and mitomycin C within 6 weeks prior to C1/D1. * Immunosuppressive or systemic hormonal therapy within 2 weeks prior to C1/D1, with exceptions. * Use of hematopoietic growth factors within 2 weeks prior to C1/D1. * Active second malignancy or history of another malignancy within the last 3 years, with exceptions. * Central nervous system (CNS) malignancy including primary malignancies of the CNS and known, untreated CNS or leptomeningeal metastases, or spinal cord compression; patients with any of these not controlled by prior surgery or radiotherapy, or symptoms suggesting CNS involvement for which treatment is required. * Inadequate recovery from an acute toxicity associated with any prior antineoplastic therapy. * Major surgical procedure within 4 weeks prior to C1/D1 or inadequate recovery from any prior surgical procedure. * Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 1 month prior to C1/D1, unless adequately treated and stable. * Active uncontrolled bleeding or a known bleeding diathesis. * Significant cardiovascular disease or condition. * Abnormal hematologic, renal or hepatic function. * Part 2 ONLY: * Radiotherapy against target lesions within 4 weeks prior to C1/D1, unless there is documented progression of the lesion following the radiotherapy. * Basket Cohort ONLY: * Prior therapy with MET-inhibiting agents (exceptions will be a subset of patients that will be entered to the Basket Cohort after having received prior therapy with a MET-targeting TKI). * Prior therapy with antibody to hepatocyte growth factor (HGF). * Basket Cohort and NSCLC MET-Amplified Cohort ONLY: * Tumor status demonstrating MET-polysomy in the absence of MET-amplification, as specified per protocol. Patients in the NSCLC METex14del Cohort with polysomy are eligible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Occurrence of DLTs During Cycle 1 of Sym015 Administration | Cycle 1, the initial 28-day period of Q2W dosing | 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. |
| Part 2: Documented, Confirmed Objective Response (OR) | 24 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Determine a Q2W RP2D of Sym015. | 12 Months | Determination based on an evaluation of the patient data for DLTs from Part 1. Q2W = every second week. RP2D = recommended phase 2 dose. |
| Immunogenicity of Sym015: Part 1. | 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) | Serum sampling was done to assess the potential for anti-drug antibody (ADA) formation. |
| Immunogenicity of Sym015: Part 2. | 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) | Serum sampling was done to assess the potential for anti-drug antibody (ADA) formation. |
| Part 1: Area Under the Concentration-time Curve in a Dosing Interval (AUC) Following 1st Dose | 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. |
| Part 2: Area Under the Concentration-time Curve in a Dosing Interval (AUC) | 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. |
| Part 1: Cmax | 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. |
| Part 2: Cmax | 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. |
| Part 1: Time to Reach Maximum Concentration (Tmax) | 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. |
| Part 2: Time to Reach Maximum Concentration (Tmax) | 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. |
| Part 1: Trough Concentration (Ctrough) | 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. |
| Part 2: Trough Concentration (Ctrough) | 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. |
| Part 1: Elimination Half-life (T½) | 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. |
| Part 2: Elimination Half-life (T½) | 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. |
| Part 1: Clearance (CL) | 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. |
| Part 2: Clearance (CL) | 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. |
| 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. | 24 Months | This 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). |
| 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. | 24 Months | This 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. |
Countries
Denmark, Hong Kong, South Korea, Spain, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Dose-Escalation, 6 mg/kg 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. | 3 |
| Part 1: Dose-Escalation, 12 mg/kg 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. | 3 |
| Part 1: Dose-Escalation 18 mg/kg 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. | 3 |
| Part 1: Dose-Escalation 24 mg/kg 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. | 3 |
| Part 2: Dose-Expansion, 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. | 25 |
| Part 2: Dose-Expansion, NSCLC MET-Amplified Cohort 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. | 8 |
| Part 2: Dose-Expansion, NSCLC METex14del Cohort 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. | 12 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| Overall Study | Other reason (unknown) | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Progressive disease | 2 | 2 | 2 | 3 | 22 | 7 | 8 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Transferred to named patient program | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1: Dose-Escalation, 12 mg/kg | Part 1: Dose-Escalation 18 mg/kg | Part 1: Dose-Escalation 24 mg/kg | Part 2: Dose-Expansion, Basket Cohort | Part 2: Dose-Expansion, NSCLC MET-Amplified Cohort | Part 2: Dose-Expansion, NSCLC METex14del Cohort | Part 1: Dose-Escalation, 6 mg/kg | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 62.0 years STANDARD_DEVIATION 11.79 | 55.3 years STANDARD_DEVIATION 11.24 | 67.3 years STANDARD_DEVIATION 7.23 | 56.6 years STANDARD_DEVIATION 11.87 | 65.6 years STANDARD_DEVIATION 8.91 | 68.5 years STANDARD_DEVIATION 9.82 | 55.7 years STANDARD_DEVIATION 14.57 | 61.1 years STANDARD_DEVIATION 11.73 |
| Age, Customized 18-65 years | 1 Participants | 2 Participants | 1 Participants | 20 Participants | 2 Participants | 6 Participants | 2 Participants | 34 Participants |
| Age, Customized 65 to <75 years | 2 Participants | 1 Participants | 2 Participants | 4 Participants | 5 Participants | 0 Participants | 1 Participants | 15 Participants |
| Age, Customized 75 to <85 years | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 6 Participants | 0 Participants | 8 Participants |
| Age, Customized 85 years or older | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Anatomic based cancer type Adenocarcinoma of Parotid Gland | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Anatomic based cancer type Adenocarcinoma of Thymus | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Anatomic based cancer type BRCA (breast cancer gene) | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Anatomic based cancer type Cholangiocarcinoma | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Anatomic based cancer type CRC (colorectal cancer) | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 2 Participants | 6 Participants |
| Anatomic based cancer type GC (gastric cancer) | 0 Participants | 0 Participants | 0 Participants | 13 Participants | 0 Participants | 0 Participants | 0 Participants | 13 Participants |
| Anatomic based cancer type GU (genitourinary cancer) | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants |
| Anatomic based cancer type HCC (hepatocellular carcinoma) | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Anatomic based cancer type HCC-MIXED | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Anatomic based cancer type HCC-Neuroendocrine | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Anatomic based cancer type Lung-Neuroendocrine | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Anatomic based cancer type Nasopharyngeal carcinoma | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Anatomic based cancer type NSCLC (non-small-cell lung carcinoma) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 7 Participants | 11 Participants | 0 Participants | 18 Participants |
| Anatomic based cancer type NSCLC- Sq type | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Anatomic based cancer type Pancreatic cancer | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Anatomic based cancer type SCC (squamous cell carcinoma) of skin/soft tissue | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Body mass index (BMI) | 23.65 kg per square meter STANDARD_DEVIATION 3.978 | 29.84 kg per square meter STANDARD_DEVIATION 7.452 | 25.89 kg per square meter STANDARD_DEVIATION 5.363 | 23.58 kg per square meter STANDARD_DEVIATION 3.776 | 22.15 kg per square meter STANDARD_DEVIATION 4.59 | 25.19 kg per square meter STANDARD_DEVIATION 4.081 | 28.10 kg per square meter STANDARD_DEVIATION 1.132 | 24.44 kg per square meter STANDARD_DEVIATION 4.405 |
| Body weight | 62.5 kg STANDARD_DEVIATION 12.03 | 89.0 kg STANDARD_DEVIATION 18.29 | 69.7 kg STANDARD_DEVIATION 8.05 | 67.1 kg STANDARD_DEVIATION 10.73 | 60.3 kg STANDARD_DEVIATION 11.58 | 72.1 kg STANDARD_DEVIATION 15.54 | 82.2 kg STANDARD_DEVIATION 17.86 | 69.1 kg STANDARD_DEVIATION 13.86 |
| ECOG-PS 0 | 2 Participants | 1 Participants | 0 Participants | 4 Participants | 2 Participants | 1 Participants | 1 Participants | 11 Participants |
| ECOG-PS 1 | 1 Participants | 2 Participants | 3 Participants | 21 Participants | 6 Participants | 9 Participants | 2 Participants | 44 Participants |
| ECOG-PS 2 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 1 Participants | 24 Participants | 8 Participants | 11 Participants | 3 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Histopathologic diagnosis Adenocarcinoma | 1 Participants | 1 Participants | 2 Participants | 22 Participants | 7 Participants | 11 Participants | 3 Participants | 47 Participants |
| Histopathologic diagnosis Missing | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 10 Participants |
| Number of sites with metastasis 0 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Number of sites with metastasis 1 | 0 Participants | 1 Participants | 0 Participants | 7 Participants | 2 Participants | 1 Participants | 1 Participants | 12 Participants |
| Number of sites with metastasis 2 | 0 Participants | 0 Participants | 0 Participants | 8 Participants | 1 Participants | 3 Participants | 1 Participants | 13 Participants |
| Number of sites with metastasis 3 | 2 Participants | 1 Participants | 1 Participants | 6 Participants | 3 Participants | 4 Participants | 0 Participants | 17 Participants |
| Number of sites with metastasis More than 3 | 1 Participants | 1 Participants | 2 Participants | 4 Participants | 2 Participants | 4 Participants | 1 Participants | 15 Participants |
| Previous debulking surgery No | 1 Participants | 2 Participants | 3 Participants | 16 Participants | 7 Participants | 12 Participants | 3 Participants | 44 Participants |
| Previous debulking surgery Yes | 2 Participants | 1 Participants | 0 Participants | 9 Participants | 1 Participants | 0 Participants | 0 Participants | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 14 Participants | 2 Participants | 1 Participants | 0 Participants | 17 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 2 Participants | 8 Participants | 6 Participants | 11 Participants | 2 Participants | 35 Participants |
| Region of Enrollment Denmark | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants | 2 participants |
| Region of Enrollment South Korea | 0 participants | 0 participants | 0 participants | 12 participants | 2 participants | 0 participants | 0 participants | 14 participants |
| Region of Enrollment Spain | 0 participants | 0 participants | 0 participants | 6 participants | 2 participants | 3 participants | 0 participants | 11 participants |
| Region of Enrollment Taiwan | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 3 participants | 3 participants | 3 participants | 6 participants | 3 participants | 8 participants | 3 participants | 29 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 2 Participants | 7 Participants | 5 Participants | 6 Participants | 1 Participants | 25 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 1 Participants | 18 Participants | 3 Participants | 6 Participants | 2 Participants | 32 Participants |
| Site of primary tumor Breast | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Site of primary tumor Colon | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 5 Participants |
| Site of primary tumor Gastrointestinal | 0 Participants | 0 Participants | 0 Participants | 11 Participants | 0 Participants | 0 Participants | 0 Participants | 11 Participants |
| Site of primary tumor Genitourinary | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants |
| Site of primary tumor Hepatic (including gallbladder) | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Site of primary tumor Liver | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Site of primary tumor Neck | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Site of primary tumor Other locally advanced sites | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 5 Participants |
| Site of primary tumor Other metastatic sites | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Site of primary tumor Pancreas | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Site of primary tumor Respiratory | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 7 Participants | 12 Participants | 0 Participants | 19 Participants |
| Site of primary tumor Skin/soft tissue | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sites with metastasis Abdomen, pelvis | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Sites with metastasis Abdominal cavity, diaphragm, subcutis, para- renal mass, Sub-Hepatic Mass | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sites with metastasis Adrenal gland | 0 Participants | 1 Participants | 0 Participants | 4 Participants | 1 Participants | 4 Participants | 0 Participants | 10 Participants |
| Sites with metastasis Bone | 0 Participants | 2 Participants | 2 Participants | 6 Participants | 2 Participants | 7 Participants | 1 Participants | 20 Participants |
| Sites with metastasis Both ovaries, peritoneum, colon | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sites with metastasis Brain | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 5 Participants |
| Sites with metastasis Duodenum | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sites with metastasis Effusion | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sites with metastasis Kidney | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Sites with metastasis Liver | 2 Participants | 0 Participants | 2 Participants | 8 Participants | 1 Participants | 2 Participants | 2 Participants | 17 Participants |
| Sites with metastasis Lungs | 2 Participants | 2 Participants | 2 Participants | 8 Participants | 7 Participants | 9 Participants | 1 Participants | 31 Participants |
| Sites with metastasis Lymph nodes | 3 Participants | 0 Participants | 3 Participants | 20 Participants | 6 Participants | 7 Participants | 2 Participants | 41 Participants |
| Sites with metastasis Lymph nodes and Lymphangitis Carcinomatoses | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sites with metastasis Muscle | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Sites with metastasis Pelvis, abdominal wall, spleen | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sites with metastasis Peritoneal | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Sites with metastasis Peritoneum, peribiliary | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sites with metastasis Pleura | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Sites with metastasis Pleural based metastases | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sites with metastasis Primary gastric cancer | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sites with metastasis Rectum | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sites with metastasis Skin | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Sites with metastasis Soft tissue | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants | 0 Participants | 8 Participants |
| Sites with metastasis Spleen, pelvis, abdomen, left ovary | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Sites with metastasis Subpleura | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sites with metastasis Thyroid gland | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Time since initial diagnosis | 2.3 years STANDARD_DEVIATION 1.53 | 10.3 years STANDARD_DEVIATION 9.29 | 2.0 years STANDARD_DEVIATION 2 | 2.1 years STANDARD_DEVIATION 2.2 | 0 years STANDARD_DEVIATION 0 | 0 years STANDARD_DEVIATION 0 | 4.7 years STANDARD_DEVIATION 2.52 | 3.5 years STANDARD_DEVIATION 4.57 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 25 | 0 / 8 | 3 / 12 |
| other Total, other adverse events | 2 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 23 / 25 | 8 / 8 | 12 / 12 |
| serious Total, serious adverse events | 1 / 3 | 1 / 3 | 0 / 3 | 1 / 3 | 8 / 25 | 4 / 8 | 6 / 12 |
Outcome results
Primary
Part 1: Occurrence of DLTs During Cycle 1 of Sym015 Administration
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.
Time frame: Cycle 1, the initial 28-day period of Q2W dosing
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Part 1: Occurrence of DLTs During Cycle 1 of Sym015 Administration | 0 Number of DLTs |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Part 1: Occurrence of DLTs During Cycle 1 of Sym015 Administration | 0 Number of DLTs |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Part 1: Occurrence of DLTs During Cycle 1 of Sym015 Administration | 0 Number of DLTs |
| Part 1: Dose-Escalation; Period 4: 24 mg/kg | Part 1: Occurrence of DLTs During Cycle 1 of Sym015 Administration | 0 Number of DLTs |
Primary
Part 2: Documented, Confirmed Objective Response (OR)
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.
Time frame: 24 months
Population: The Full Analysis Set (FAS) comprised all enrolled patients who had received at least one dose of Sym015.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Part 2: Documented, Confirmed Objective Response (OR) | 0 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Part 2: Documented, Confirmed Objective Response (OR) | 2 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Part 2: Documented, Confirmed Objective Response (OR) | 3 Participants |
Secondary
Immunogenicity of Sym015: Part 1.
Serum sampling was done to assess the potential for anti-drug antibody (ADA) formation.
Time frame: 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.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 1. | End of treatment | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 1 - day 1 | Negative | 3 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 1. | End of treatment | Negative | 3 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 1. | End of treatment | Patient withdrawn | 0 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 1 - day 1 | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 1 - day 1 | Patient withdrawn | 0 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 1. | 1-month follow-up | Negative | 2 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 3 - day 1 | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 3 - day 1 | Negative | 1 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 3 - day 1 | Patient withdrawn | 2 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 1. | 1-month follow-up | Patient withdrawn | 1 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 1. | 1-month follow-up | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 1 - day 1 | Patient withdrawn | 0 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 1. | End of treatment | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 1 - day 1 | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 1. | End of treatment | Patient withdrawn | 1 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 1. | 1-month follow-up | Patient withdrawn | 1 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 1. | End of treatment | Negative | 2 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 3 - day 1 | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 1. | 1-month follow-up | Not done | 1 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 1 - day 1 | Negative | 3 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 3 - day 1 | Patient withdrawn | 3 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 1. | 1-month follow-up | Negative | 1 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 3 - day 1 | Negative | 0 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 1. | End of treatment | Negative | 1 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 3 - day 1 | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 1 - day 1 | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 1 - day 1 | Negative | 3 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 1 - day 1 | Patient withdrawn | 0 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 3 - day 1 | Negative | 2 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 3 - day 1 | Patient withdrawn | 1 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 1. | End of treatment | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 1. | End of treatment | Patient withdrawn | 2 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 1. | 1-month follow-up | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 1. | 1-month follow-up | Negative | 0 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 1. | 1-month follow-up | Patient withdrawn | 3 Participants |
| Part 1: Dose-Escalation; Period 4: 24 mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 3 - day 1 | Patient withdrawn | 3 Participants |
| Part 1: Dose-Escalation; Period 4: 24 mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 3 - day 1 | Negative | 0 Participants |
| Part 1: Dose-Escalation; Period 4: 24 mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 3 - day 1 | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 4: 24 mg/kg | Immunogenicity of Sym015: Part 1. | 1-month follow-up | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 4: 24 mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 1 - day 1 | Patient withdrawn | 0 Participants |
| Part 1: Dose-Escalation; Period 4: 24 mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 1 - day 1 | Negative | 3 Participants |
| Part 1: Dose-Escalation; Period 4: 24 mg/kg | Immunogenicity of Sym015: Part 1. | 1-month follow-up | Patient withdrawn | 1 Participants |
| Part 1: Dose-Escalation; Period 4: 24 mg/kg | Immunogenicity of Sym015: Part 1. | 1-month follow-up | Negative | 2 Participants |
| Part 1: Dose-Escalation; Period 4: 24 mg/kg | Immunogenicity of Sym015: Part 1. | End of treatment | Negative | 2 Participants |
| Part 1: Dose-Escalation; Period 4: 24 mg/kg | Immunogenicity of Sym015: Part 1. | End of treatment | Not done | 1 Participants |
| Part 1: Dose-Escalation; Period 4: 24 mg/kg | Immunogenicity of Sym015: Part 1. | Cycle 1 - day 1 | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 4: 24 mg/kg | Immunogenicity of Sym015: Part 1. | End of treatment | Patient withdrawn | 0 Participants |
Secondary
Immunogenicity of Sym015: Part 2.
Serum sampling was done to assess the potential for anti-drug antibody (ADA) formation.
Time frame: 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.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | 1-month follow up | Patient withdrawn | 14 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 7 - day 1 | Patient withdrawn | 23 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 3 - day 1 | Positive | 0 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 1 - day 1 | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 7 - day 1 | Positive | 0 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 3 - day 1 | Patient withdrawn | 16 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 2 - day 1 | Not done | 1 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 7 - day 1 | Negative | 2 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 5 - day 1 | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | 1-month follow up | Positive | 1 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 7 - day 1 | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 5 - day 1 | Negative | 6 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | 1-month follow up | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 5 - day 1 | Patient withdrawn | 19 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 5 - day 1 | Positive | 0 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 2 - day 1 | Negative | 21 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 1 - day 1 | Positive | 0 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | End of treatment | Patient withdrawn | 4 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 2 - day 1 | Positive | 0 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 1 - day 1 | Negative | 25 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | End of treatment | Positive | 1 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 2 - day 1 | Patient withdrawn | 3 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | 1-month follow up | Negative | 10 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | End of treatment | Negative | 15 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 3 - day 1 | Not done | 1 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 1 - day 1 | Patient withdrawn | 0 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | End of treatment | Not done | 5 Participants |
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 3 - day 1 | Negative | 8 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | 1-month follow up | Not done | 1 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 1 - day 1 | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 1 - day 1 | Negative | 8 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 1 - day 1 | Positive | 0 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 1 - day 1 | Patient withdrawn | 0 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 2 - day 1 | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 2 - day 1 | Negative | 8 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 2 - day 1 | Positive | 0 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 2 - day 1 | Patient withdrawn | 0 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 3 - day 1 | Not done | 1 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 3 - day 1 | Negative | 7 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 3 - day 1 | Positive | 0 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 3 - day 1 | Patient withdrawn | 0 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 5 - day 1 | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 5 - day 1 | Negative | 6 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 5 - day 1 | Positive | 0 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 5 - day 1 | Patient withdrawn | 2 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 7 - day 1 | Not done | 1 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 7 - day 1 | Negative | 2 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 7 - day 1 | Positive | 0 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 7 - day 1 | Patient withdrawn | 5 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | End of treatment | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | End of treatment | Negative | 7 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | End of treatment | Positive | 0 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | End of treatment | Patient withdrawn | 1 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | 1-month follow up | Negative | 3 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | 1-month follow up | Positive | 0 Participants |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Immunogenicity of Sym015: Part 2. | 1-month follow up | Patient withdrawn | 4 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 7 - day 1 | Positive | 0 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 3 - day 1 | Negative | 8 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 1 - day 1 | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 7 - day 1 | Patient withdrawn | 7 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 3 - day 1 | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | 1-month follow up | Negative | 5 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | End of treatment | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 2 - day 1 | Patient withdrawn | 1 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 1 - day 1 | Negative | 12 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | End of treatment | Negative | 9 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 2 - day 1 | Positive | 0 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | 1-month follow up | Patient withdrawn | 6 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | End of treatment | Positive | 0 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 2 - day 1 | Negative | 11 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | 1-month follow up | Positive | 0 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | End of treatment | Patient withdrawn | 3 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 5 - day 1 | Positive | 0 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 5 - day 1 | Negative | 5 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 2 - day 1 | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 5 - day 1 | Patient withdrawn | 6 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 5 - day 1 | Not done | 1 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 1 - day 1 | Patient withdrawn | 0 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 7 - day 1 | Not done | 0 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 3 - day 1 | Patient withdrawn | 4 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | 1-month follow up | Not done | 1 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 7 - day 1 | Negative | 5 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 3 - day 1 | Positive | 0 Participants |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Immunogenicity of Sym015: Part 2. | Cycle 1 - day 1 | Positive | 0 Participants |
Secondary
Part 1: Area Under the Concentration-time Curve in a Dosing Interval (AUC) Following 1st Dose
Estimated using non-compartmental methods and actual time points following the first dose of Sym015.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Part 1: Area Under the Concentration-time Curve in a Dosing Interval (AUC) Following 1st Dose | 17900 h*μg/mL |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Part 1: Area Under the Concentration-time Curve in a Dosing Interval (AUC) Following 1st Dose | 35700 h*μg/mL |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Part 1: Area Under the Concentration-time Curve in a Dosing Interval (AUC) Following 1st Dose | 82500 h*μg/mL |
| Part 1: Dose-Escalation; Period 4: 24 mg/kg | Part 1: Area Under the Concentration-time Curve in a Dosing Interval (AUC) Following 1st Dose | 76800 h*μg/mL |
Secondary
Part 1: Clearance (CL)
Estimated using non-compartmental methods and actual time points.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Part 1: Clearance (CL) | 0.3 mL/h |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Part 1: Clearance (CL) | 0.2 mL/h |
Secondary
Part 1: Cmax
Maximum serum concentration was derived from observed data.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Part 1: Cmax | 146 ug/mL |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Part 1: Cmax | 286 ug/mL |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Part 1: Cmax | 563 ug/mL |
| Part 1: Dose-Escalation; Period 4: 24 mg/kg | Part 1: Cmax | 561 ug/mL |
Secondary
Part 1: Determine a Q2W RP2D of Sym015.
Determination based on an evaluation of the patient data for DLTs from Part 1. Q2W = every second week. RP2D = recommended phase 2 dose.
Time frame: 12 Months
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Part 1: Determine a Q2W RP2D of Sym015. | NA mg/kg |
Secondary
Part 1: Elimination Half-life (T½)
Estimated using non-compartmental methods and actual time points.
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Part 1: Elimination Half-life (T½) | 179 hours |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Part 1: Elimination Half-life (T½) | 137 hours |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Part 1: Elimination Half-life (T½) | 193 hours |
| Part 1: Dose-Escalation; Period 4: 24 mg/kg | Part 1: Elimination Half-life (T½) | 170 hours |
Secondary
Part 1: Time to Reach Maximum Concentration (Tmax)
Time to reach maximum concentration (Tmax) was derived from observed data.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Part 1: Time to Reach Maximum Concentration (Tmax) | 2.1 hours |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Part 1: Time to Reach Maximum Concentration (Tmax) | 1.1 hours |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Part 1: Time to Reach Maximum Concentration (Tmax) | 3.5 hours |
| Part 1: Dose-Escalation; Period 4: 24 mg/kg | Part 1: Time to Reach Maximum Concentration (Tmax) | 3.0 hours |
Secondary
Part 1: Trough Concentration (Ctrough)
Ctrough was derived from observed data.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Part 1: Trough Concentration (Ctrough) | 23.1 μg/mL |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Part 1: Trough Concentration (Ctrough) | 61.3 μg/mL |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Part 1: Trough Concentration (Ctrough) | 130 μg/mL |
| Part 1: Dose-Escalation; Period 4: 24 mg/kg | Part 1: Trough Concentration (Ctrough) | 92.4 μg/mL |
Secondary
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.
This 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.
Time frame: 24 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | 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 |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | 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. | 8 Participants |
Secondary
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.
This 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).
Time frame: 24 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | 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 |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | 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 |
Secondary
Part 2: Area Under the Concentration-time Curve in a Dosing Interval (AUC)
Estimated using non-compartmental methods and actual time points following the first dose of Sym015 for the whole basket cohort.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Part 2: Area Under the Concentration-time Curve in a Dosing Interval (AUC) | 34000 h*ug/mL |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Part 2: Area Under the Concentration-time Curve in a Dosing Interval (AUC) | 37200 h*ug/mL |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Part 2: Area Under the Concentration-time Curve in a Dosing Interval (AUC) | 38700 h*ug/mL |
Secondary
Part 2: Clearance (CL)
Estimated using non-compartmental methods and actual time points following the first dose of Sym015 for the whole basket cohort.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Part 2: Clearance (CL) | 0.4 mL/h/kg |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Part 2: Clearance (CL) | 0.2 mL/h/kg |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Part 2: Clearance (CL) | 0.2 mL/h/kg |
Secondary
Part 2: Cmax
Maximum serum concentration was derived from observed data following the first dose of Sym015 for the full basket cohort.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Part 2: Cmax | 420 ug/mL |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Part 2: Cmax | 520 ug/mL |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Part 2: Cmax | 510 ug/mL |
Secondary
Part 2: Elimination Half-life (T½)
Estimated using non-compartmental methods and actual time points following the first dose of Sym015 for the whole basket cohort.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Part 2: Elimination Half-life (T½) | 150 hours |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Part 2: Elimination Half-life (T½) | 191 hours |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Part 2: Elimination Half-life (T½) | 171 hours |
Secondary
Part 2: Time to Reach Maximum Concentration (Tmax)
Time to reach maximum concentration (Tmax) was derived from observed data following the first dose of Sym015 for the full basket cohort.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Part 2: Time to Reach Maximum Concentration (Tmax) | 2.5 hours |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Part 2: Time to Reach Maximum Concentration (Tmax) | 3.7 hours |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Part 2: Time to Reach Maximum Concentration (Tmax) | 2.8 hours |
Secondary
Part 2: Trough Concentration (Ctrough)
Ctrough was derived from observed data following the first dose of Sym015 for the whole basket cohort.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Dose-Escalation; Period 1, 6 mg/kg | Part 2: Trough Concentration (Ctrough) | 84.1 μg/mL |
| Part 1: Dose-Escalation; Period 2: 12mg/kg | Part 2: Trough Concentration (Ctrough) | 90.1 μg/mL |
| Part 1: Dose-Escalation; Period 3:18mg/kg | Part 2: Trough Concentration (Ctrough) | 101.7 μg/mL |