Samuraciclib for the Treatment of Patients With Resectable, Borderline Resectable, or Locally Advanced Basal Pancreatic Cancer

This is a single-institution, single-arm, open-label, Phase 1 study designed to evaluate whether samuraciclib, a cyclin dependent kinase 7 inhibitor (CDK7), alters the cellular functioning of the pancreatic tumor cells.

OUTLINE:

Patients will receive samuraciclib orally (PO) once daily (QD) for 14 days on study following their diagnosis of pancreatic cancer and before starting chemotherapy or undergoing surgery for their cancer. Patients will undergo an endoscopic ultrasound (EUS) with fine needle biopsy (FNB) while on study.

After completion of study treatment, patients are followed up at 30 and 90 days.

• Samuraciclib (Drug), also known as CDK7 Inhibitor CT7001, CT 7001, CT-7001, CT7001: Given PO
• Computed Tomography (Procedure), also known as CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography: Undergo CT
• Endoscopic Ultrasound Biopsy (Procedure): Undergo EUS/FNB
• Biospecimen Collection (Procedure), also known as Biological Sample Collection, Biospecimen Collected, Specimen Collection: Undergo blood sample collection

Primary outcomes

• Change in ribonucleic acid polymerase II serine levels [Within 72 hours post versus pre-samuraciclib treatment]: Will be assessed by pharmacodynamic changes in primary tumor cells. Pre and post measurements will be compared using a paired t-test at the 2-sided 5% level. Data will be transformed as necessary (e.g. using log-transformation).

Secondary outcomes

• Incidence of samuraciclib-related adverse events [Within 30 days of the last dose of samuraciclib]: Will be measured by Common Terminology Criteria for Adverse Events version 6.
• Completion of 14 days of study drug (Feasibility) [Up to 90 days]: Will be summarized by proportions and 90% confidence intervals using the Wilson score method.
• Completion of the on-protocol research endoscopic ultrasound/fine needle biopsy (Feasibility) [Up to 90 days]: Will be summarized by proportions and 90% confidence intervals using the Wilson score method.
• Adequate biopsy (≥ 3 cores with ≥30% tumor cellularity) (Feasibility) [Up to 90 days]: Will be summarized by proportions and 90% confidence intervals using the Wilson score method.
• Time (days) from last dose of study drug to first definitive therapy (surgery or cycle 1 day 1 of neoadjuvant chemotherapy) [Up to 90 days]: Will be estimated using the Kaplan Meier method.
• Incidence of schedule delays attributable to study drug [Up to 90 days]: Will be summarized by proportions and 90% confidence intervals using the Wilson score method.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Histologically or cytologically proven basal pancreatic adenocarcinoma. Histologies other than adenocarcinoma, or any mixed histologies, will NOT be eligible.

  * Basal tumors are defined as GATA6- and HMGA2+. Tumor cores are considered positive for GATA6 or HMGA2 if greater than 10% of tumor epithelial cells had positive nuclei
* Resectable, borderline resectable, or locally advanced pancreatic ductal adenocarcinoma (PDA) at diagnosis based on contrast-enhanced CT or magnetic resonance imaging (MRI) (CT or MRI without contrast as part of positron emission tomography (PET)/CT or PET/MRI is NOT acceptable; CT or MRI with contrast as part PET/CT or PET/MRI is acceptable) of the chest, abdomen, and pelvis. The institutional radiologist must review the scans. Resectable, borderline resectable, and locally advanced will be defined by National Comprehensive Cancer Network (NCCN) guidelines version 2.2025.

  * There must be no evidence of metastatic disease
* Must be 18 years or older
* Ability to understand and willingness to sign a written informed consent document
* Archival biopsy specimen collected within 3 months must be available. If not available, a diagnostic EUS/FNB will be performed during screening
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Absolute neutrophil count (ANC) ≥ 1,500/mcL (within 14 days prior to study drug)
* Platelets ≥ 100,000/mcL (within 14 days prior to study drug)
* Hemoglobin ≥ 9 g/dL (within 14 days prior to study drug)
* Creatinine clearance ≥ 50 ml/min by Cockcroft-Gault
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both ≤ 2.5X ULN (within 14 days prior to study drug)
* Total bilirubin ≤ 1.5X ULN (within 14 days prior to study drug)
* Participants must not be pregnant or nursing. Women of childbearing potential (WOCBP) must have a negative urine pregnancy test within 72 hours of treatment initiation, where WOCBP are defined as all female participants between 18 - 55 years of age. Participants of child-bearing potential must be willing to employ two highly effective and acceptable forms of contraception for up to 6 months after the final administered dose of investigational agent. A woman is considered to be of reproductive potential if she has had menses at any time in the preceding 12 consecutive months
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

Exclusion Criteria:

* Prior radiation
* Unable to tolerate oral medication, per assessment of the principal investigator (PI)
* Participants who are receiving other investigational agents
* Concomitant mediation use should only exclude patients from trial participation when clinically relevant known or predicted drug-drug interactions or potential overlapping toxicities will impact safety or efficacy
* Uncontrolled or concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Refractory nausea and vomiting, chronic gastrointestinal diseases or previous significant bowel resection with clinically significant sequelae that precluded adequate absorption of samuraciclib
* Uncontrolled seizures
* Active infection
* Active bleeding diatheses
* Known active hepatitis B or hepatitis C infection
* Breastfeeding or pregnancy
* Receipt of systemic corticosteroids within 14 days before the first dose of study medication
* Receipt of St. John's Wort within 21 days before the first dose of study medication or of another concomitant medication, herbal supplement, or food that was a strong inhibitor or inducer of CYP3A4, CYP2C19, CYP2D6, or P-glycoprotein activity within 21 days before the first dose of samuraciclib
* Known hypersensitivity to samuraciclib or any excipient of the product

• Andrew Coveler, MD, Principal investigator, Fred Hutch/University of Washington Cancer Consortium