Parts A and B (monotherapy and combination with SoC): Number of participants with DLTs
Adverse events (AEs) graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 considered DLTs:
All grade 5 events not clearly related to disease progression or any other causes
Any grade 3 or higher non-hematologic toxicity regardless of duration
Hy's law cases
Any grade 2 pneumonitis that does not resolve to grade 1 within 3 days of the initiation of maximal supportive care
Recurrent grade 2 pneumonitis
Grade 4 neutropenia lasting more than 7 days
Febrile neutropenia
Grade 3 thrombocytopenia with bleeding
Grade 4 thrombocytopenia
AEs NOT considered DLTs:
Grade 3 nausea, vomiting, or diarrhea that can be controlled within 72 hours
Grade 3 fatigue less than 5 days
Grade 3 or higher correctable electrolyte abnormalities that last less than 72 hours and not associated with clinical complications
Grade 3 or higher amylase or lipase not associated with clinical manifestations of pancreatitis
Parts A and B (monotherapy and combination with SoC): Number of participants with treatment-emergent AEs (TEAEs)
A TEAE is defined as an AE that:
emerges during SOT102 treatment, having been absent at the time of pre-treatment (screening), or
re-emerges during SOT102 treatment, having been present at the time of pre-treatment (screening), or
worsens in severity during SOT102 treatment relative to the pre-treatment state if the AE is continuous.
Parts A and B (monotherapy and combination with SoC): Number of participants with SOT102-related AEs
Causal relationship (relatedness) of all AEs will be assessed by investigators and classified as follows:
Not suspected: It is not plausible that the AE is caused by medication/procedure and a likely alternative explanation exists. No reasonable possibility of a causal or temporal relationship.
Suspected: It is plausible that the AE is caused by medication/procedure. Reasonable possibility of a causal relationship.
Parts A and B (monotherapy and combination with SoC): Number of participants with serious AEs (SAEs)
An SAE is any untoward medical occurrence that at any dose fulfills one or more of the following criteria:
Results in death
Is immediately life-threatening
Results in persistent or significant disability/incapacity
Is a congenital anomaly/birth defect
Requires inpatient hospitalization or prolongation of existing hospitalization
Is another medically significant event defined as an event that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent any of the above listed outcomes
Parts A and B (monotherapy and combination with SoC): Number of participants with AEs leading to premature discontinuation of SOT102
AEs (intercurrent illness or trial treatment-related toxicity) that would, in the judgment of the investigator, affect assessments of clinical status to a significant degree or require discontinuation of trial treatment
Parts A and B (monotherapy and combination with SoC): Number of participants who died
Date of death and immediate and underlying causes of death will be collected.
Parts A and B (monotherapy and combination with SoC): Number of participants with clinical laboratory test abnormalities (coagulation, hematology, clinical chemistry and urinalysis) of grade 3 or higher graded according to NCI CTCAE version 5.0
The following laboratory parameters will be assessed:
Coagulation: prothrombin time, INR
Hematology: leukocytes, erythrocytes, hemoglobin, hematocrit, platelets, differential
Clinical chemistry: ALT, albumin, ALP, amylase, AST, bilirubin, blood urea nitrogen or blood urea, calcium, creatinine, glucose (fasting), LDH, lipase, magnesium, potassium, sodium, TSH (gastric adenocarcinoma only)
Urinalysis: blood, glucose, ketones, pH, protein, specific gravity, urine leukocyte esterase
Parts A and B (monotherapy and combination with SoC): Characterization of pharmacokinetics (PK) of total SOT102 and its derivates
Assessment of concentration of SOT102 and its derivates at various timepoints
Parts A and B (monotherapy and combination with SoC): Evidence of SOT102 activity in monotherapy in individual patients
Detection of anecdotal tumor response in individual patient, as per RECIST 1.1 criteria
Parts A and B (monotherapy and combination with SoC): Number of participants with antibodies against SOT102
Identification of patients who develop detectable antibodies against any part of SOT102
Parts C and D (monotherapy and combination with SoC): Duration of response (DoR) according to RECIST 1.1
The DoR is defined as the time from the first achieved response (complete or partial, confirmed) until the first date of radiological progression or death.
Parts C and D (monotherapy and combination with SoC): Progression-free survival (PFS) according to RECIST 1.1
PFS is defined as the time from trial enrolment until the first date of radiological progression or death.
Part C (monotherapy): Clinical benefit rate (CBR) according to RECIST 1.1
The CBR is defined as the number of complete responses, partial responses, and stable diseases from all evaluable best overall responses.
Parts C and D (monotherapy and combination with SoC): Overall survival (OS)
OS is defined as the time from eligibility verification until the date of death.
Parts C and D (monotherapy and combination with SoC): Number of participants with TEAEs
A TEAE is defined as an AE that:
emerges during SOT102 treatment, having been absent at the time of pre-treatment (screening), or
re-emerges during SOT102 treatment, having been present at the time of pre-treatment (screening), or
worsens in severity during SOT102 treatment relative to the pre-treatment state if the AE is continuous.
Parts C and D (monotherapy and combination with SoC): Number of participants with SOT102-related AEs
Causal relationship (relatedness) of all AEs will be assessed by investigators and classified as follows:
Not suspected: It is not plausible that the AE is caused by medication/procedure and a likely alternative explanation exists. No reasonable possibility of a causal or temporal relationship.
Suspected: It is plausible that the AE is caused by medication/procedure. Reasonable possibility of a causal relationship.
Parts C and D (monotherapy and combination with SoC): Number of participants with SAEs
An SAE is any untoward medical occurrence that at any dose fulfills one or more of the following criteria:
Results in death
Is immediately life-threatening
Results in persistent or significant disability/incapacity
Is a congenital anomaly/birth defect
Requires inpatient hospitalization or prolongation of existing hospitalization
Is another medically significant event defined as an event that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent any of the above listed outcomes
Parts C and D (monotherapy and combination with SoC): Number of participants with AEs leading to premature discontinuation of SOT102
AEs (intercurrent illness or trial treatment-related toxicity) that would, in the judgment of the investigator, affect assessments of clinical status to a significant degree or require discontinuation of trial treatment
Parts C and D (monotherapy and combination with SoC): Number of participants who died
Date of death and immediate and underlying causes of death will be collected.
Parts C and D (monotherapy and combination with SoC): Number of participants with clinical laboratory test abnormalities (coagulation, hematology, clinical chemistry and urinalysis) of grade 3 or higher graded according to NCI CTCAE version 5.0
The following laboratory parameters will be assessed:
Coagulation: prothrombin time, INR
Hematology: leukocytes, erythrocytes, hemoglobin, hematocrit, platelets, differential
Clinical chemistry: ALT, albumin, ALP, amylase, AST, bilirubin, blood urea nitrogen or blood urea, calcium, creatinine, glucose (fasting), LDH, lipase, magnesium, potassium, sodium, TSH (gastric adenocarcinoma only)
Urinalysis: blood, glucose, ketones, pH, protein, specific gravity, urine leukocyte esterase
Parts C and D (monotherapy and combination with SoC, patients with gastric cancer): Patient-reported quality of life questionnaire EORTC QLQ-C30 scores
To determine the effect of trial intervention on the quality of life.
Parts C and D (monotherapy and combination with SoC, patients with gastric cancer): Patient-reported quality of life questionnaire EORTC QLQ-STO22 scores
To determine the effect of trial intervention on the quality of life.
Parts C and D (monotherapy and combination with SoC, patients with pancreatic cancer): Patient-reported quality of life questionnaire EORTC QLQ-C30 scores
To determine the effect of trial intervention on the quality of life.
Parts C and D (monotherapy and combination with SoC, patients with pancreatic cancer): Patient-reported quality of life questionnaire EORTC QLQ-PAN26 scores
To determine the effect of trial intervention on the quality of life.
Parts C and D (monotherapy and combination with SoC): Patient-reported quality of life questionnaire EQ-5D-3L scores
To determine the effect of trial intervention on the quality of life.
Parts C and D (monotherapy and combination with SoC): Characterization of PK of total SOT102 and its derivates
Assessment of concentration of SOT102 and its derivates at various timepoints
Parts C and D (monotherapy and combination with SoC): Number of participants with antibodies against SOT102
Identification of patients who develop detectable antibodies against any part of SOT102