A Study of SLC-0111 and Gemcitabine for Metastatic Pancreatic Ductal Cancer in Subjects Positive for CAIX

Who cannot take part

• Previous treatment with any known CAIX Inhibitor
• History of myocardial infarction, unstable angina, congestive heart failure (New York Heart Association class ≥ III/IV), cerebrovascular accident, transient ischaemic attack, limb claudication at rest in the 6 months prior to enrolment, or ongoing symptomatic dysrhythmias, or uncontrolled atrial or ventricular arrhythmias, or uncontrolled hypertension
• Any condition or illness that, in the opinion of the Investigator would compromise subject safety or interfere with the evaluation of the safety of the investigational products
• Hypersensitivity to investigational products or their excipients or severe allergy to sulfonamides
• Refractory nausea and vomiting, chronic gastrointestinal diseases, gastrointestinal bleeding, ulceration, or perforation within 12 weeks prior to the first administration of investigational products or significant bowel resection that would preclude adequate absorption
• Known acute hepatitis B infection or chronic hepatitis B not currently on suppressive therapy
• Severe cardiac disease which has required hospitalization within the past 3 months or which functionally limits a patient
• Severe respiratory illness requiring supplemental oxygen or that significantly impacts functional status in daily life
• Subjects with documented cases of human immunodeficiency virus (HIV) and viral load detectable
• Known hepatitis C antibody positive and RNA positive. Subjects with hepatitis C antibody positivity but RNA negativity may enroll after consultation with hepatology
• Active uncontrolled bacterial, viral, or fungal infections
• Malignancy within the preceding 5 years (Subjects may be included in the trial if malignancy was a non-melanoma skin cancer, ductal carcinoma in-situ, early cervical malignancy, or at the discretion of the primary investigator if the malignancy has had curative intent treatment and has a < 10% chance of recurring within 5 years as per a well-recognized risk stratification tool specific for that malignancy.); Additional Dose Expansion Exclusion Criteria:; Subjects cannot be enrolled in the dose expansion if they were enrolled during the dose escalation of the current study
• Subjects negative for CAIX via IHC (biopsy or archival tissue)
• Females who are pregnant, planning to become pregnant or breastfeeding
• Untreated CNS metastasis or CNS metastasis that has not been clinically stable for 28 days

Other criteria

• Pre-Screening Inclusion Criteria:
• Males or females aged ≥ 18 years old
• Able and willing to provide written pre-screening informed consent and to comply with the study protocol and procedures
• A biopsiable tumour and a willingness to provide biopsies if no archival tumour tissue exists
• Histologically or cytologically-confirmed metastatic pancreatic ductal adenocarcinoma (this can include distant lymph nodes). Subjects with locally advanced disease or regional lymph node involvement are to be excluded; Regional lymph nodes are considered: Lymph nodes superior and inferior to head and body of pancreas, anterior and posterior pancreaticoduodenal, pyloric, proximal mesenteric nodes, and common bile duct lymph nodes, splenic hilar, pancreatic tail, peripancreatic, hepatic artery, infrapyloric (head only), subpyloric (head only), celiac (head only), superior mesenteric, pancreaticolienal (body and tail only), splenic (body and tail only), retroperitoneal, lateral aortic
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Life expectancy greater than 3 months in the investigator's opinion
• Subject (archival tissue or pre-treatment biopsy) must be positive for CAIX via IHC before screening assessments listed below begin (i.e. Study Inclusion and Exclusion Criteria); Main Study Inclusion Criteria:
• Males or females aged ≥ 18 years old
• Able and willing to provide written informed consent and to comply with the study protocol and procedures
• Histologically or cytologically-confirmed metastatic pancreatic ductal adenocarcinoma (this can include distant lymph nodes). Subjects with locally advanced disease or regional lymph node involvement are to be excluded; Regional lymph nodes are considered: Lymph nodes superior and inferior to head and body of pancreas, anterior and posterior pancreaticoduodenal, pyloric, proximal mesenteric nodes, and common bile duct lymph nodes, splenic hilar, pancreatic tail, peripancreatic, hepatic artery, infrapyloric (head only), subpyloric (head only), celiac (head only), superior mesenteric, pancreaticolienal (body and tail only), splenic (body and tail only), retroperitoneal, lateral aortic
• ≥1 prior line of systemic therapy with a 14-day washout period or if investigational combination is being considered for first line of therapy, subject was not eligible for FOLFIRINOX or gemcitabine + nab-paclitaxel
• Recovery to ≤ Grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancies
• ECOG performance status 0 or 1
• Life expectancy greater than 3 months in the Investigator's opinion
• The following time must have elapsed between previous therapy for cancer or medical history event and first administration of SLC-0111 and gemcitabine:; At least 2 weeks since previous cancer-directed therapy (cytotoxic agents, targeted therapy including monoclonal antibody therapy, immunotherapy, hormonal therapy, and prior radiotherapy); At least 2 weeks or five times the elimination half-life (whichever is shortest) of any investigational drug/biologic or combination product prior to first dose of study treatment; At least 4 weeks since any major surgery; At least 12 weeks since any incidence of severe gastrointestinal bleeding
• Adequate renal function:; Creatinine ≤ 1.5 times upper limit of normal (ULN) or calculated creatinine clearance (CrCl) using the Cockcroft Gault formula ≥ 60 mL/min, or measured CrCl ≥ 60 mL/min
• Adequate hepatic function:; Serum total bilirubin ≤ 1.5 times upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN (≤ 5 x ULN if liver lesions present [i.e. liver metastasis or primary tumour of the liver for HCC])
• Adequate hematologic function (without G-CSF support):; Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L; Platelets ≥ 100 x 10\^9/L; Hemoglobin ≥ 85 g/L
• Adequate coagulation tests:; INR ≤ 1.5; PTT ≤ 1.5 times ULN
• Corrected QT interval (QTc) < 470 ms
• Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption
• Negative pregnancy test in female subjects of child-bearing potential (defined as women who have not undergone hysterectomy/oophorectomy or who have not been naturally post-menopausal for ≥ 12 months)
• Subjects must agree not to donate gametes (oocyte or sperm) during study and for 4 months following last dose of study treatment
• Sexually active subjects (male and female) must agree to use acceptable methods of contraception to avoid pregnancy prior to start of dosing, during the course of the study and for 4 months after the last dose of study treatment
• Collect post-treatment biopsy if the tumour is biopsiable and a willingness to provide biopsies exists (optional); Additional Inclusion Criteria for Dose Expansion (Part 2):
• Measurable disease as per RECIST 1.1