Clinical Trial of SOT102 Antibody Drug Conjugate in Patients With Advanced Gastric and Pancreatic Adenocarcinoma

Phase 2TerminatedNCT05525286

SOTIO Biotech a.s.31 enrolled

Overview

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.

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)

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Pancreatic Cancer

Interventions

SOT102DRUG

SOT102 is an antibody-drug conjugate (ADC) targeting CLDN18.2 with the anthracycline PNU as cytotoxic moiety.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (8)

Washington University School of Medicine in St. Louis

St Louis, Missouri, United States

Cleveland Clinic Main Campus

Cleveland, Ohio, United States

Institut Jules Bordet

Brussels, Belgium

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, Belgium

Outcomes

Primary Outcomes

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)

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

Secondary Outcomes

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

Data from ClinicalTrials.gov

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Masarykův Onkologický Ústav

Brno, Czechia

Institut Gustave Roussy

Paris, France

VHIO - Vall d'Hebron Institut d'Oncologia

Barcelona, Spain

Hospital Universitario HM Sanchinarro

Madrid, Spain

Time frame: Through Cycles 1-2 (28 days)

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.