Pancreatic Cancer
Conditions
Keywords
Pancreatic Cancer, Advanced Cancer, Metastatic Cancer
Brief summary
This trial will assess the MTD and RP2D of SOT102 administered as monotherapy (Part A) and in combination with first-line SoC treatment (nab-paclitaxel/ gemcitabine; Part B) and efficacy of SOT102 administered as monotherapy (Part C) and in combination with first-line SoC treatment (Part D) in patients with advanced or metastatic pancreatic adenocarcinoma.
Detailed description
The trial will have the following parts: * Part A: Dose escalation, first-in-human, single-agent phase 1 trial of SOT102 in advanced/metastatic pancreatic cancer patients with unmet medical need (CLDN18.2 agnostic) * Part B : Phase 1b dose escalation combination trial of SOT102 in combination with nab-paclitaxel/gemcitabine as SoC regimen for first-line treatment of patients with advanced/metastatic pancreatic cancer (CLDN18.2 agnostic) Once an RP2D in the respective phase 1 evaluation (Part A and Part B) has been identified, expansion parts (Part C and Part D) are planned: * Part C : Single-agent SOT102 expansion at RP2D identified in Part A in pancreatic cancer after one or more prior systemic therapies (second+ line) for locally advanced or metastatic disease (CLDN18.2 positive) * Part D : SOT102 in combination with nab- paclitaxel/gemcitabine for first-line treatment expansion at RP2D identified in Part B in pancreatic cancer (CLDN18.2 positive)
Interventions
DRUGSOT102
SOT102 is an antibody-drug conjugate (ADC) targeting CLDN18.2 with the anthracycline PNU as cytotoxic moiety.
Sponsors
SOTIO Biotech a.s.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
SN201 is a multi-modular clinical trial in patients with pancreatic adenocarcinoma.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
All Parts (key criteria) * Hematologic: Absolute neutrophil count ≥1.5×10⁹/L, platelets ≥100×10⁹/L, hemoglobin ≥9 g/dL * Hepatic: Bilirubin ≤1.5× upper limits of normal (ULN), ALT and AST ≤2.5×ULN; in case of liver involvement: AST and ALT ≤5×ULN * Renal: Creatinine clearance ≥60 mL/min calculated by Cockcroft-Gault formula * Prothrombin time/international normalized ratio (INR) ≤1.5×ULN * Albumin ≥3.0 mg/dL * Proteinuria \<1 g/24 hours * Eastern Cooperative Oncology Group (ECOG) performance status ≤1 * Estimated life expectancy ≥3 months as per investigator's assessment * A female patient is eligible to participate if she is not pregnant, not breastfeeding, not of childbearing potential/ agreed with contraception Part A * Patient has advanced inoperable or metastatic disease * Patient has no better treatment option available * Measurable or non-measurable disease according to RECIST 1.1 * Histological or cytological evidence of adenocarcinoma of pancreas that is advanced or metastatic Part B (in addition to relevant A criteria)\*Histological or cytological evidence of adenocarcinoma of the pancreas that is advanced or metastatic (pancreas) Part C (in addition to relevant A criteria)\*Must have received at least one prior systemic therapy for advanced or metastatic disease (pancreas) Part D (in addition to relevant B criteria)\*Histological or cytological evidence of adenocarcinoma of the pancreas that is advanced inoperable or metastatic (pancreas)
Exclusion criteria
All Parts (key criteria) * Patient has received radiation therapy ≤14 days before day 1 of cycle 1 or has not recovered to grade ≤1 from treatment-related side effects * Severe preexisting medical conditions as per judgement of the investigator (e.g., active gastric or GEJ ulcer with or without bleeding, complete or incomplete gastric outlet syndrome with persistent or repetitive bleeding) * History of interstitial pneumonitis or pulmonary fibrosis * Symptomatic central nervous system malignancy. Patients with asymptomatic or treated central nervous system metastases may be eligible if they are not treated with corticosteroids or anticonvulsants and the disease is stable for at least 60 days. * Patient has peripheral sensory neuropathy grade ≥2 * Active infection requiring systemic therapy within ≤7 days prior to day 1 of cycle 1 * History of major ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, Torsades de Pointes) * Bradycardia (\<50 beats per minute) * Family history of sudden cardiac death before age 50 * History or family history of congenital long QT syndrome * Major surgical intervention ≤28 days prior to ICF signature or incomplete wound healing after surgical intervention * Time since last transfusion of RBCs ≤14 days before cycle 1 day 1 * Vaccination with a live or live-attenuated vaccine within 30 days prior the first dose of trial interventions Part B/D (key) \*Patients with contraindications to any component of the first-line SoC treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Parts A and B: The Definition of the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of SOT102 Given as Monotherapy and in Combination With First-line SoC Treatment | Through Cycles 1-2 (28 days) | MTD is defined as the highest dose level tested below the dose level associated with ≥33% of dose-limiting toxicity (DLT)-evaluable patients experiencing a DLT. The RP2D will be selected based on evaluation of the totality of all data. The trial was halted early due to safety signals not initially deemed DLTs that were seen across different dose levels. After a protocol amendment formally defined this signal as a DLT, the trial was restarted, but the same safety signal reappeared. Following a review by the independent Dose Escalation Committee, the trial was terminated. |
| Parts C and D: The Assessment of the Efficacy of SOT102 in Monotherapy and in Combination With First-line SoC Treatment | From Day 1 of Cycle 1 until disease progression or start of new anticancer therapy, whichever is first, to be assessed up to approximately 4 years | Efficacy is determined by objective response rate (ORR) determined according to RECIST 1.1 criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Parts A and B (Monotherapy and Combination With SoC): Number of Participants With SOT102-related AEs | Day 1 up to approximately 2 years and 8.5 months | 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. |
| Part B (Combination With SoC): Number of Participants With SoC-related AEs | Day 1 up to approximately 2 years and 8.5 months | 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) | Day 1 up to approximately 2 years and 8.5 months | 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 | Day 1 up to approximately 2 years and 8.5 months | 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 |
| Part B (Combination With SoC): Number of Participants With AEs Leading to Premature Discontinuation of SoC | Day 1 up to approximately 2 years and 8.5 months | 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 | Day 1 up to approximately 2 years and 8.5 months | 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 | Day 1 up to approximately 2 years and 8.5 months | 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): Number of Participants With Treatment-emergent AEs (TEAEs) | Day 1 up to approximately 2 years and 8.5 months | 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): Characterization of Tmax of SOT102 | From Day 1 of Cycle 1 until Day 1 of Cycle 5 | Assessment of concentration of SOT102 and its derivates at various timepoints |
| Parts A and B (Monotherapy and Combination With SoC): Characterization of AUClast of SOT102 | From Day 1 of Cycle 1 until Day 1 of Cycle 5 | 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 - BOR: Complete Response | From Day 1 of Cycle 1 until disease progression or start of new anticancer therapy, whichever is first, assessed up to approximately 2 years and 9 months | Detection of anecdotal tumor response in individual patient, as per RECIST 1.1 criteria |
| Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Partial Response | From Day 1 of Cycle 1 until disease progression or start of new anticancer therapy, whichever is first, assessed up to approximately 2 years and 9 months | Detection of anecdotal tumor response in individual patient, as per RECIST 1.1 criteria |
| Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Stable Disease | From Day 1 of Cycle 1 until disease progression or start of new anticancer therapy, whichever is first, assessed up to approximately 2 years and 9 months | 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 | From Day 1 of Cycle 1 until 30 (+5) days after the last dose of SOT102, assessed up to approximately 2 years and 9 months | Identification of patients who develop detectable antibodies against any part of SOT102 |
| Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Progressive Disease | From Day 1 of Cycle 1 until disease progression or start of new anticancer therapy, whichever is first, assessed up to approximately 2 years and 9 months | Detection of anecdotal tumor response in individual patient, as per RECIST 1.1 criteria |
| Parts A and B (Monotherapy and Combination With SoC): Characterization of Cmax of SOT102 | From Day 1 of Cycle 1 until Day 1 of Cycle 5 | Assessment of concentration of SOT102 and its derivates at various timepoints |
| Parts A and B (Monotherapy and Combination With SoC): Number of Participants With DLTs | Through Cycles 1-2 (28 days) | 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; Grade 2 or higher serum creatinine elevation; 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 2 or higher proteinuria; 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 |
Countries
Belgium, Czechia, France, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SOT102 as Monotherapy (Part A) DL1 0.032 mg/kg Patients with CLDN18.2-positive pancreatic adenocarcinoma were treated with 0.032 mg/kg of SOT102 given once every 14 days via the IV route over 45 (±15) minutes. | 4 |
| SOT102 as Monotherapy (Part A) DL2 0.046 mg/kg Patients with CLDN18.2-positive pancreatic adenocarcinoma were treated with 0.064 mg/kg of SOT102 given once every 14 days via the IV route over 45 (±15) minutes. | 11 |
| SOT102 as Monotherapy (Part A) DL3 0.128 mg/kg Patients with CLDN18.2-positive pancreatic adenocarcinoma were treated with 0.128 mg/kg of SOT102 given once every 14 days via the IV route over 45 (±15) minutes. | 9 |
| SOT102 as Monotherapy (Part A) DL4 0.214 mg/kg Patients with CLDN18.2-positive pancreatic adenocarcinoma were treated with 0.214 mg/kg of SOT102 given once every 14 days via the IV route over 45 (±15) minutes. | 3 |
| SOT102 in Combination With SoC (Part B) 0.032 mg/kg Patients with CLDN18.2-positive pancreatic adenocarcinoma were treated with 0.032 mg/kg of SOT102 given once every 14 days via the IV route over 45 (±15) minutes. Upon completion of the SOT102 infusion, first-line SoC treatment was administered. SoC treatment was nab-paclitaxel (125 mg/m2) given as a 30- to 40-minute infusion followed by gemcitabine (1000 mg/m2) given as a 30-minute infusion on days 1, 8, and 15. This treatment was repeated every 28 days. | 4 |
| Total | 31 |
Baseline characteristics
| Characteristic | SOT102 as Monotherapy (Part A) DL1 0.032 mg/kg | SOT102 as Monotherapy (Part A) DL2 0.046 mg/kg | SOT102 as Monotherapy (Part A) DL3 0.128 mg/kg | SOT102 as Monotherapy (Part A) DL4 0.214 mg/kg | SOT102 in Combination With SoC (Part B) 0.032 mg/kg | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 0 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 10 Participants | 6 Participants | 1 Participants | 4 Participants | 24 Participants |
| Age, Continuous | 55.5 years STANDARD_DEVIATION 6.95 | 55.4 years STANDARD_DEVIATION 9.62 | 57.6 years STANDARD_DEVIATION 9.67 | 65.3 years STANDARD_DEVIATION 2.08 | 51.8 years STANDARD_DEVIATION 2.63 | 56.5 years STANDARD_DEVIATION 8.55 |
| BSA at baseline | 1.90 square meters STANDARD_DEVIATION 0.271 | 1.89 square meters STANDARD_DEVIATION 0.311 | 1.86 square meters STANDARD_DEVIATION 0.288 | 1.67 square meters STANDARD_DEVIATION 0.379 | 1.83 square meters STANDARD_DEVIATION 0.263 | 1.86 square meters STANDARD_DEVIATION 0.287 |
| ECOG status 0 | 2 Participants | 4 Participants | 3 Participants | 2 Participants | 2 Participants | 13 Participants |
| ECOG status 1 | 2 Participants | 7 Participants | 6 Participants | 1 Participants | 2 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 7 Participants | 7 Participants | 1 Participants | 4 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 2 Participants | 2 Participants | 0 Participants | 8 Participants |
| Height at baseline | 1.74 meters STANDARD_DEVIATION 0.12 | 1.74 meters STANDARD_DEVIATION 0.135 | 1.73 meters STANDARD_DEVIATION 0.107 | 1.67 meters STANDARD_DEVIATION 0.195 | 1.69 meters STANDARD_DEVIATION 0.101 | 1.72 meters STANDARD_DEVIATION 0.121 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 2 Participants | 2 Participants | 0 Participants | 8 Participants |
| Race (NIH/OMB) White | 4 Participants | 7 Participants | 7 Participants | 1 Participants | 4 Participants | 23 Participants |
| Region of Enrollment Belgium | 0 participants | 3 participants | 3 participants | 1 participants | 1 participants | 8 participants |
| Region of Enrollment Czechia | 2 participants | 0 participants | 3 participants | 0 participants | 3 participants | 8 participants |
| Region of Enrollment France | 0 participants | 3 participants | 1 participants | 1 participants | 0 participants | 5 participants |
| Region of Enrollment Spain | 2 participants | 2 participants | 2 participants | 1 participants | 0 participants | 7 participants |
| Region of Enrollment United States | 0 participants | 3 participants | 0 participants | 0 participants | 0 participants | 3 participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 4 Participants | 2 Participants | 2 Participants | 12 Participants |
| Sex: Female, Male Male | 3 Participants | 8 Participants | 5 Participants | 1 Participants | 2 Participants | 19 Participants |
| Weight at baseline | 77.8 kilograms STANDARD_DEVIATION 16.58 | 75.5 kilograms STANDARD_DEVIATION 22.3 | 72.7 kilograms STANDARD_DEVIATION 18.08 | 62.7 kilograms STANDARD_DEVIATION 21.02 | 72.4 kilograms STANDARD_DEVIATION 19.54 | 73.4 kilograms STANDARD_DEVIATION 19.08 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 4 | 5 / 11 | 3 / 9 | 1 / 3 | 0 / 4 |
| other Total, other adverse events | 4 / 4 | 9 / 11 | 8 / 9 | 3 / 3 | 4 / 4 |
| serious Total, serious adverse events | 4 / 4 | 5 / 11 | 5 / 9 | 2 / 3 | 0 / 4 |
Outcome results
Primary
Parts A and B: The Definition of the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of SOT102 Given as Monotherapy and in Combination With First-line SoC Treatment
MTD is defined as the highest dose level tested below the dose level associated with ≥33% of dose-limiting toxicity (DLT)-evaluable patients experiencing a DLT. The RP2D will be selected based on evaluation of the totality of all data. The trial was halted early due to safety signals not initially deemed DLTs that were seen across different dose levels. After a protocol amendment formally defined this signal as a DLT, the trial was restarted, but the same safety signal reappeared. Following a review by the independent Dose Escalation Committee, the trial was terminated.
Time frame: Through Cycles 1-2 (28 days)
Population: DLT evaluable patients were those who have received 2 doses of SOT102 per schedule (day 1 of cycle 1 and day 1 of cycle 2) with the maximum postponement of cycle 2 by 1 day (as agreed by the sponsor) and completed the evaluation period of 28 days. Also patients who experienced a treatment emergent adverse event at any time during the DLT evaluation period that met the definition of a DLT.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT102 as Monotherapy (Part A) | Parts A and B: The Definition of the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of SOT102 Given as Monotherapy and in Combination With First-line SoC Treatment | NA Participants |
| SOT102 in Combination With SoC (Part B) | Parts A and B: The Definition of the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of SOT102 Given as Monotherapy and in Combination With First-line SoC Treatment | NA Participants |
Primary
Parts C and D: The Assessment of the Efficacy of SOT102 in Monotherapy and in Combination With First-line SoC Treatment
Efficacy is determined by objective response rate (ORR) determined according to RECIST 1.1 criteria
Time frame: From Day 1 of Cycle 1 until disease progression or start of new anticancer therapy, whichever is first, to be assessed up to approximately 4 years
Population: Part C and Part D were not initiated, no population was analyzed.
Secondary
Part B (Combination With SoC): Number of Participants With AEs Leading to Premature Discontinuation of SoC
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
Time frame: Day 1 up to approximately 2 years and 8.5 months
Population: Patients exposed to at least one dose of SoC
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT102 in Combination With SoC (Part B) DL1 0.032 mg/kg | Part B (Combination With SoC): Number of Participants With AEs Leading to Premature Discontinuation of SoC | 1 Participants |
Secondary
Part B (Combination With SoC): Number of Participants With SoC-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.
Time frame: Day 1 up to approximately 2 years and 8.5 months
Population: Patients exposed to at least one dose of SoC
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT102 in Combination With SoC (Part B) DL1 0.032 mg/kg | Part B (Combination With SoC): Number of Participants With SoC-related AEs | 4 Participants |
Secondary
Parts A and B (Monotherapy and Combination With SoC): Characterization of AUClast of SOT102
Assessment of concentration of SOT102 and its derivates at various timepoints
Time frame: From Day 1 of Cycle 1 until Day 1 of Cycle 5
Population: Patients who had at least 1 post-dose concentration measurement above the lower limit of quantification. No data was collected for Part B due to the low number of patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SOT102 as Monotherapy (Part A) | Parts A and B (Monotherapy and Combination With SoC): Characterization of AUClast of SOT102 | 44558.9495 h*ng/mL |
| SOT102 in Combination With SoC (Part B) | Parts A and B (Monotherapy and Combination With SoC): Characterization of AUClast of SOT102 | 108104.0701 h*ng/mL |
| SOT102 as Monotherapy (Part A) DL3 0.128 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Characterization of AUClast of SOT102 | 321146.7316 h*ng/mL |
| SOT102 as Monotherapy (Part A) DL4 0.214 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Characterization of AUClast of SOT102 | 605136.8688 h*ng/mL |
Secondary
Parts A and B (Monotherapy and Combination With SoC): Characterization of Cmax of SOT102
Assessment of concentration of SOT102 and its derivates at various timepoints
Time frame: From Day 1 of Cycle 1 until Day 1 of Cycle 5
Population: Patients who had at least 1 post-dose concentration measurement above the lower limit of quantification. No data was collected for Part B due to the low number of patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SOT102 as Monotherapy (Part A) | Parts A and B (Monotherapy and Combination With SoC): Characterization of Cmax of SOT102 | 564.1750 ng/mL |
| SOT102 in Combination With SoC (Part B) | Parts A and B (Monotherapy and Combination With SoC): Characterization of Cmax of SOT102 | 1220.3250 ng/mL |
| SOT102 as Monotherapy (Part A) DL3 0.128 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Characterization of Cmax of SOT102 | 2792.6000 ng/mL |
| SOT102 as Monotherapy (Part A) DL4 0.214 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Characterization of Cmax of SOT102 | 4980.6000 ng/mL |
Secondary
Parts A and B (Monotherapy and Combination With SoC): Characterization of Tmax of SOT102
Assessment of concentration of SOT102 and its derivates at various timepoints
Time frame: From Day 1 of Cycle 1 until Day 1 of Cycle 5
Population: Patients who had at least 1 post-dose concentration measurement above the lower limit of quantification. No data was collected for Part B due to the low number of patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SOT102 as Monotherapy (Part A) | Parts A and B (Monotherapy and Combination With SoC): Characterization of Tmax of SOT102 | 0.217 hours |
| SOT102 in Combination With SoC (Part B) | Parts A and B (Monotherapy and Combination With SoC): Characterization of Tmax of SOT102 | 0.217 hours |
| SOT102 as Monotherapy (Part A) DL3 0.128 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Characterization of Tmax of SOT102 | 0.233 hours |
| SOT102 as Monotherapy (Part A) DL4 0.214 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Characterization of Tmax of SOT102 | 0.233 hours |
Secondary
Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Complete Response
Detection of anecdotal tumor response in individual patient, as per RECIST 1.1 criteria
Time frame: From Day 1 of Cycle 1 until disease progression or start of new anticancer therapy, whichever is first, assessed up to approximately 2 years and 9 months
Population: Patients exposed to at least one dose of SOT102 who had at least one evaluable tumor assessment per RECIST v1.1 after the initiation of SOT102 treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT102 as Monotherapy (Part A) | Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Complete Response | 0 Participants |
| SOT102 in Combination With SoC (Part B) | Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Complete Response | 0 Participants |
| SOT102 as Monotherapy (Part A) DL3 0.128 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Complete Response | 0 Participants |
| SOT102 as Monotherapy (Part A) DL4 0.214 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Complete Response | 0 Participants |
| SOT102 in Combination With SoC (Part B) DL1 0.032 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Complete Response | 0 Participants |
Secondary
Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Partial Response
Detection of anecdotal tumor response in individual patient, as per RECIST 1.1 criteria
Time frame: From Day 1 of Cycle 1 until disease progression or start of new anticancer therapy, whichever is first, assessed up to approximately 2 years and 9 months
Population: Patients exposed to at least one dose of SOT102 who had at least one evaluable tumor assessment per RECIST v1.1 after the initiation of SOT102 treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT102 as Monotherapy (Part A) | Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Partial Response | 0 Participants |
| SOT102 in Combination With SoC (Part B) | Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Partial Response | 0 Participants |
| SOT102 as Monotherapy (Part A) DL3 0.128 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Partial Response | 0 Participants |
| SOT102 as Monotherapy (Part A) DL4 0.214 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Partial Response | 0 Participants |
| SOT102 in Combination With SoC (Part B) DL1 0.032 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Partial Response | 1 Participants |
Secondary
Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Progressive Disease
Detection of anecdotal tumor response in individual patient, as per RECIST 1.1 criteria
Time frame: From Day 1 of Cycle 1 until disease progression or start of new anticancer therapy, whichever is first, assessed up to approximately 2 years and 9 months
Population: Patients exposed to at least one dose of SOT102 who had at least one evaluable tumor assessment per RECIST v1.1 after the initiation of SOT102 treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT102 as Monotherapy (Part A) | Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Progressive Disease | 1 Participants |
| SOT102 in Combination With SoC (Part B) | Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Progressive Disease | 5 Participants |
| SOT102 as Monotherapy (Part A) DL3 0.128 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Progressive Disease | 6 Participants |
| SOT102 as Monotherapy (Part A) DL4 0.214 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Progressive Disease | 2 Participants |
| SOT102 in Combination With SoC (Part B) DL1 0.032 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Progressive Disease | 0 Participants |
Secondary
Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Stable Disease
Detection of anecdotal tumor response in individual patient, as per RECIST 1.1 criteria
Time frame: From Day 1 of Cycle 1 until disease progression or start of new anticancer therapy, whichever is first, assessed up to approximately 2 years and 9 months
Population: Patients exposed to at least one dose of SOT102 who had at least one evaluable tumor assessment per RECIST v1.1 after the initiation of SOT102 treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT102 as Monotherapy (Part A) | Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Stable Disease | 1 Participants |
| SOT102 in Combination With SoC (Part B) | Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Stable Disease | 3 Participants |
| SOT102 as Monotherapy (Part A) DL3 0.128 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Stable Disease | 2 Participants |
| SOT102 as Monotherapy (Part A) DL4 0.214 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Stable Disease | 1 Participants |
| SOT102 in Combination With SoC (Part B) DL1 0.032 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Evidence of SOT102 Activity in Monotherapy in Individual Patients - BOR: Stable Disease | 3 Participants |
Secondary
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.
Time frame: Day 1 up to approximately 2 years and 8.5 months
Population: Patients exposed to at least one dose of SOT102
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT102 as Monotherapy (Part A) | Parts A and B (Monotherapy and Combination With SoC): Number of Participants Who Died | 2 Participants |
| SOT102 in Combination With SoC (Part B) | Parts A and B (Monotherapy and Combination With SoC): Number of Participants Who Died | 5 Participants |
| SOT102 as Monotherapy (Part A) DL3 0.128 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants Who Died | 3 Participants |
| SOT102 as Monotherapy (Part A) DL4 0.214 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants Who Died | 1 Participants |
| SOT102 in Combination With SoC (Part B) DL1 0.032 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants Who Died | 0 Participants |
Secondary
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
Time frame: Day 1 up to approximately 2 years and 8.5 months
Population: Patients exposed to at least one dose of SOT102
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT102 as Monotherapy (Part A) | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With AEs Leading to Premature Discontinuation of SOT102 | 0 Participants |
| SOT102 in Combination With SoC (Part B) | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With AEs Leading to Premature Discontinuation of SOT102 | 1 Participants |
| SOT102 as Monotherapy (Part A) DL3 0.128 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With AEs Leading to Premature Discontinuation of SOT102 | 3 Participants |
| SOT102 as Monotherapy (Part A) DL4 0.214 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With AEs Leading to Premature Discontinuation of SOT102 | 1 Participants |
| SOT102 in Combination With SoC (Part B) DL1 0.032 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With AEs Leading to Premature Discontinuation of SOT102 | 0 Participants |
Secondary
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
Time frame: From Day 1 of Cycle 1 until 30 (+5) days after the last dose of SOT102, assessed up to approximately 2 years and 9 months
Population: Patients exposed to at least one dose of SOT102
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT102 as Monotherapy (Part A) | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With Antibodies Against SOT102 | 3 Participants |
| SOT102 in Combination With SoC (Part B) | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With Antibodies Against SOT102 | 2 Participants |
| SOT102 as Monotherapy (Part A) DL3 0.128 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With Antibodies Against SOT102 | 3 Participants |
| SOT102 as Monotherapy (Part A) DL4 0.214 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With Antibodies Against SOT102 | 0 Participants |
| SOT102 in Combination With SoC (Part B) DL1 0.032 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With Antibodies Against SOT102 | 0 Participants |
Secondary
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
Time frame: Day 1 up to approximately 2 years and 8.5 months
Population: Patients exposed to at least one dose of SOT102
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT102 as Monotherapy (Part A) | 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 | 3 Participants |
| SOT102 in Combination With SoC (Part B) | 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 | 2 Participants |
| SOT102 as Monotherapy (Part A) DL3 0.128 mg/kg | 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 | 3 Participants |
| SOT102 as Monotherapy (Part A) DL4 0.214 mg/kg | 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 | 0 Participants |
| SOT102 in Combination With SoC (Part B) DL1 0.032 mg/kg | 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 | 1 Participants |
Secondary
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; Grade 2 or higher serum creatinine elevation; 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 2 or higher proteinuria; 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
Time frame: Through Cycles 1-2 (28 days)
Population: Patients who received 2 doses of SOT102 per schedule (day 1 of cycle 1 and day 1 of cycle 2). Patients must have completed evaluation period of 28 days. Pancreatic patients must have received three doses of SoC (days 1, 8, and 15 of cycle 1), gastric patients must have received 2 doses of SoC per schedule (day 1 of cycle 1 and day 1 of cycle 2). Patients who experienced an adverse event at any time during the DLT evaluation period that met the definition of a DLT were included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT102 as Monotherapy (Part A) | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With DLTs | 0 Participants |
| SOT102 in Combination With SoC (Part B) | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With DLTs | 1 Participants |
| SOT102 as Monotherapy (Part A) DL3 0.128 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With DLTs | 1 Participants |
| SOT102 as Monotherapy (Part A) DL4 0.214 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With DLTs | 0 Participants |
| SOT102 in Combination With SoC (Part B) DL1 0.032 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With DLTs | 0 Participants |
Secondary
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
Time frame: Day 1 up to approximately 2 years and 8.5 months
Population: Patients exposed to at least one dose of SOT102
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT102 as Monotherapy (Part A) | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With Serious AEs (SAEs) | 4 Participants |
| SOT102 in Combination With SoC (Part B) | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With Serious AEs (SAEs) | 5 Participants |
| SOT102 as Monotherapy (Part A) DL3 0.128 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With Serious AEs (SAEs) | 5 Participants |
| SOT102 as Monotherapy (Part A) DL4 0.214 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With Serious AEs (SAEs) | 2 Participants |
| SOT102 in Combination With SoC (Part B) DL1 0.032 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With Serious AEs (SAEs) | 0 Participants |
Secondary
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.
Time frame: Day 1 up to approximately 2 years and 8.5 months
Population: Patients exposed to at least one dose of SOT102
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT102 as Monotherapy (Part A) | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With SOT102-related AEs | 3 Participants |
| SOT102 in Combination With SoC (Part B) | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With SOT102-related AEs | 4 Participants |
| SOT102 as Monotherapy (Part A) DL3 0.128 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With SOT102-related AEs | 6 Participants |
| SOT102 as Monotherapy (Part A) DL4 0.214 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With SOT102-related AEs | 2 Participants |
| SOT102 in Combination With SoC (Part B) DL1 0.032 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With SOT102-related AEs | 2 Participants |
Secondary
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.
Time frame: Day 1 up to approximately 2 years and 8.5 months
Population: Patients exposed to at least one dose of SOT102
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOT102 as Monotherapy (Part A) | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With Treatment-emergent AEs (TEAEs) | 4 Participants |
| SOT102 in Combination With SoC (Part B) | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With Treatment-emergent AEs (TEAEs) | 10 Participants |
| SOT102 as Monotherapy (Part A) DL3 0.128 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With Treatment-emergent AEs (TEAEs) | 9 Participants |
| SOT102 as Monotherapy (Part A) DL4 0.214 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With Treatment-emergent AEs (TEAEs) | 3 Participants |
| SOT102 in Combination With SoC (Part B) DL1 0.032 mg/kg | Parts A and B (Monotherapy and Combination With SoC): Number of Participants With Treatment-emergent AEs (TEAEs) | 4 Participants |