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

The purpose of this study is to evaluate the safety and efficacy of samuraciclib in patients with localized 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.

Drug: Samuraciclib. Given PO

Procedure: Computed Tomography. Undergo CT

Procedure: Endoscopic Ultrasound Biopsy. Undergo EUS/FNB

Procedure: Biospecimen Collection. Undergo blood sample collection

Treatment (Samuraciclib) (experimental): Patients receive samuraciclib PO QD for 14 days on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients will have a research EUS/FNB on study. Patients also undergo CT scans during screening and blood sample collection on study.

Change in ribonucleic acid polymerase II serine levels. 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). Time frame: Within 72 hours post versus pre-samuraciclib treatment.

Incidence of samuraciclib-related adverse events. Time frame: Within 30 days of the last dose of samuraciclib.

Completion of 14 days of study drug (Feasibility). Time frame: Up to 90 days.

Completion of the on-protocol research endoscopic ultrasound/fine needle biopsy (Feasibility). Time frame: Up to 90 days.

Adequate biopsy (≥ 3 cores with ≥30% tumor cellularity) (Feasibility). Time frame: Up to 90 days.

Time (days) from last dose of study drug to first definitive therapy (surgery or cycle 1 day 1 of neoadjuvant chemotherapy). Time frame: Up to 90 days.

Incidence of schedule delays attributable to study drug. Time frame: Up to 90 days.

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: * …

Enrollment: 15 participants (estimated).