Clinical trial NCT05525286: Clinical Trial of SOT102 Antibody Drug Conjugate in Patients With Advanced Gastric and Pancreatic Adenocarcinoma
Official title: A Multicentric Phase 1/2 Trial to Evaluate the Safety and Efficacy of SOT102 as Monotherapy and in Combination With Standard of Care Treatment in Patients With Gastric and Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Pancreatic Cancer
Keywords: Pancreatic Cancer
Advanced Cancer
Metastatic Cancer
Lead sponsor: Sotio Biotech Inc.
Sponsor class: INDUSTRY
First posted: 2022-09-01
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: SN201 is a multi-modular clinical trial in patients with pancreatic adenocarcinoma.
Primary purpose: TREATMENT

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)

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Through Cycles 1-2 (28 days)
measure: Parts C and D: The assessment of the efficacy of SOT102 in monotherapy and in combination with first-line SoC treatment
timeFrame: From Day 1 of Cycle 1 until disease progression or start of new anticancer therapy, whichever is first, assessed up to approximately 4 years
Secondary outcomes:
measure: Parts A and B (monotherapy and combination with SoC): Number of participants with DLTs
timeFrame: Through Cycles 1-2 (28 days)
measure: Parts A and B (monotherapy and combination with SoC): Number of participants with treatment-emergent AEs (TEAEs)
timeFrame: From Day 1 of Cycle 1 until 30 (+5) days after the last dose of SOT102, assessed up to approximately 4 years
measure: Parts A and B (monotherapy and combination with SoC): Number of participants with SOT102-related AEs
timeFrame: From Day 1 of Cycle 1 until 30 (+5) days after the last dose of SOT102, assessed up to approximately 4 years
measure: Parts A and B (monotherapy and combination with SoC): Number of participants with serious AEs (SAEs)
timeFrame: From the date of the patient's signing the Informed Consent Form (ICF) until 30 (+5) days after the last dose of SOT102, assessed up to approx. 4 years; SAEs with a suspected causal relationship to SOT102 per the investigator's judgment: at any time
measure: Parts A and B (monotherapy and combination with SoC): Number of participants with AEs leading to premature discontinuation of SOT102
timeFrame: From Day 1 of Cycle 1 until the end of SOT102 treatment, assessed up to approximately 4 years
measure: Parts A and B (monotherapy and combination with SoC): Number of participants who died
timeFrame: From the date of the patient's signing the ICF until disease progression or start of new anticancer therapy, whichever is first, assessed up to approximately 4 years
measure: 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
timeFrame: From the date of the patient's signing the ICF until 30 (+5) days after the last dose of SOT102, assessed up to approximately 4 years
measure: Parts A and B (monotherapy and combination with SoC): Characterization of pharmacokinetics (PK) of total SOT102 and its derivates
timeFrame: From Day 1 of Cycle 1 until Day 1 of Cycle 5
measure: Parts A and B (monotherapy and combination with SoC): Evidence of SOT102 activity in monotherapy in individual patients
timeFrame: From Day 1 of Cycle 1 until disease progression or start of new anticancer therapy, whichever is first, assessed up to approximately 4 years
measure: Parts A and B (monotherapy and combination with SoC): Number of participants with antibodies against SOT102
timeFrame: From Day 1 of Cycle 1 until 30 (+5) days after the last dose of SOT102, assessed up to approximately 4 years
measure: Parts C and D (monotherapy and combination with SoC): Duration of response (DoR) according to RECIST 1.1
timeFrame: From Day 1 of Cycle 1 until disease progression or start of new anticancer therapy, whichever is first, assessed up to approximately 4 years
measure: Parts C and D (monotherapy and combination with SoC): Progression-free survival (PFS) according to RECIST 1.1
timeFrame: From Day 1 of Cycle 1 until disease progression or start of new anticancer therapy, whichever is first, assessed up to approximately 4 years
measure: Part C (monotherapy): Clinical benefit rate (CBR) according to RECIST 1.1
timeFrame: From Day 1 of Cycle 1 until disease progression or start of new anticancer therapy, whichever is first, assessed up to approximately 4 years
measure: Parts C and D (monotherapy and combination with SoC): Overall survival (OS)
timeFrame: From Day 1 of Cycle 1 until the end of the trial, assessed up to approximately 4 years
measure: Parts C and D (monotherapy and combination with SoC): Number of participants with TEAEs
timeFrame: From Day 1 of Cycle 1 until 30 (+5) days after the last dose of SOT102, assessed up to approximately 4 years
measure: Parts C and D (monotherapy and combination with SoC): Number of participants with SOT102-related AEs
timeFrame: From Day 1 of Cycle 1 until 30 (+5) days after the last dose of SOT102, assessed up to approximately 4 years
measure: Parts C and D (monotherapy and combination with SoC): Number of participants with SAEs
timeFrame: From the date of the patient's signing the ICF until 30 (+5) days after the last dose of SOT102, assessed up to approximately 4 years; SAEs with a suspected causal relationship to SOT102 per the investigator's judgment: at any time
measure: Parts C and D (monotherapy and combination with SoC): Number of participants with AEs leading to premature discontinuation of SOT102
timeFrame: From Day 1 of Cycle 1 until the end of SOT102 treatment, assessed up to approximately 4 years
measure: Parts C and D (monotherapy and combination with SoC): Number of participants who died
timeFrame: From the date of the patient's signing the ICF until the end of the trial, assessed up to approximately 4 years
measure: 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
timeFrame: From the date of the patient's signing the ICF until 30 (+5) days after the last dose of SOT102, assessed up to approximately 4 years
measure: Parts C and D (monotherapy and combination with SoC, patients with gastric cancer): Patient-reported quality of life questionnaire EORTC QLQ-C30 scores
timeFrame: From the date of the patient's signing the ICF until 30 (+5) days after the last dose of SOT102, assessed up to approximately 4 years
measure: Parts C and D (monotherapy and combination with SoC, patients with gastric cancer): Patient-reported quality of life questionnaire EORTC QLQ-STO22 scores
timeFrame: From the date of the patient's signing the ICF until 30 (+5) days after the last dose of SOT102, assessed up to approximately 4 years
measure: Parts C and D (monotherapy and combination with SoC, patients with pancreatic cancer): Patient-reported quality of life questionnaire EORTC QLQ-C30 scores
timeFrame: From the date of the patient's signing the ICF until 30 (+5) days after the last dose of SOT102, assessed up to approximately 4 years
measure: Parts C and D (monotherapy and combination with SoC, patients with pancreatic cancer): Patient-reported quality of life questionnaire EORTC QLQ-PAN26 scores
timeFrame: From the date of the patient's signing the ICF until 30 (+5) days after the last dose of SOT102, assessed up to approximately 4 years
measure: Parts C and D (monotherapy and combination with SoC): Patient-reported quality of life questionnaire EQ-5D-3L scores
timeFrame: From the date of the patient's signing the ICF until the end of the trial, assessed up to approximately 4 years
measure: Parts C and D (monotherapy and combination with SoC): Characterization of PK of total SOT102 and its derivates
timeFrame: From Day 1 of Cycle 1 until the end of SOT102 treatment, assessed up to approximately 4 years
measure: Parts C and D (monotherapy and combination with SoC): Number of participants with antibodies against SOT102
timeFrame: From Day 1 of Cycle 1 until the end of SOT102 treatment, assessed up to approximately 4 years
Other outcomes:
measure: Parts C and D (monotherapy and combination with SoC): Relationship between the intensity of CLDN18.2 expression and clinical outcome
timeFrame: From Day 1 of Cycle 1 until the end of SOT102 treatment, assessed up to approximately 4 years
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: Cleveland
country: United States
facility: Cleveland Clinic Main Campus
state: Ohio
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven - Campus Gasthuisberg
city: Brno
country: Czechia
facility: Masarykův Onkologický Ústav
city: Paris
country: France
facility: Institut Gustave Roussy
city: Barcelona
country: Spain
facility: VHIO - Vall d'Hebron Institut d'Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
Study officials:
affiliation: Vall d'Hebron University Hospital (HUVH)
name: Josep Tabernero, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: