A Phase I/IIa Study of EF-009 in Patients With Pancreatic Cancer

This study is a multi center, open-label, dose escalation, Phase I/IIa study of EF-009 in up to 30 patients with borderline resectable and unresectable pancreatic cancer.

In Phase I, the study will follow a "3+3" design to determine the maximum tolerated dose (MTD) of EF-009 implanted surgically in patients with pancreatic cancer. The MTD is defined as one dose level (cohort) below the dose in which dose limiting toxicities (DLTs) were observed in ≥ 33% of the participants. Phase IIa is a single arm study with up to 12 subjects in order to test the hypothesis that the MTD of EF-009 will increase the overall survival (OS) and progression free survival (PFS) in patients with borderline resectable and unresectable pancreatic cancer. The number of EF-009 implanted will be based on the MTD dose determined in the Phase I portion of the study. In both the Phase I and Phase IIa portions of the study, subjects will be evaluated for response every 8 weeks after EF-009 wafer implantation for up to 2 years, by CT, PET/CT or MRI (per treating investigator's discretion) using the same method as at baseline. Tumor measurements will be assessed based on the Response Evaluation Criteria in Solid Tumors guidelines version 1.1 (RECIST v1.1). The total study duration for each subject consists of screening, treatment, and extended follow-up period and survival follow-up period.

Drug: EF-009. Subjects who meet the eligibility criteria will have completed following evaluations and assessments before receiving treatment: a) review of medical and medication history; b) physical examination, vital signs and documentation of ECOG; c) ECG; d) routine serum biochemical, hematologic, urine pregnancy (if applicable) and urine laboratory assessments; and e) evaluation of European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 score. On Day 0, subjects will undergo EF-009 wafer implantation via laparoscopy

EF-009 (experimental): In both the Phase I and Phase IIa portions of the study, subjects will be evaluated for response every 8 weeks after EF-009 wafer implantation for up to 2 years, by CT, PET/CT or MRI (per treating investigator's discretion) using the same method as at baseline. Tumor measurements will be assessed based on the Response Evaluation Criteria in Solid Tumors guidelines version 1.1 (RECIST v1.1). The total study duration for each subject consists of screening, treatment, and extended follow-up period and survival follow-up period.

Maximum Tolerated Dose (MTD). Phase I Time frame: 21 days.

Overall survival. Phase IIa Time frame: 2 years.

Progression Free Survival. Time frame: 2 years.

Proportion of subjects underwent pancreatic resection surgery after the EF-009 wafer implantation. Time frame: 2 years.

Time to pancreatic resection surgery after the EF-009 wafer implantation. Time frame: 2 years.

Objective response rate. Time frame: 2 years.

Best response rate. Time frame: 2 years.

Time to objective tumor response. Time frame: 2 years.

Inclusion Criteria: 1. Female or male, age ≥ 18 years old 2. Subject has cytological, histological, or pathological confirmation of pancreatic cancer Note: All histologic subtype(s) of exocrine and endocrine pancreatic cancer are eligible to enroll in the study 3. Borderline resectable or unresectable pancreatic cancer judged by the PI in consultation with the designated site radiologist and surgeon at the treating institution Borderline resectable tumors are those that have: 1. no distant metastases; 2. venous involvement of the superior mesenteric vein (SMV)/portal vein (PV) with or without impingement and narrowing of the lumen; 3. short segment venous occlusion but with suitable vessel proximal and distal to occlusion, allowing for safe resection and reconstruction; 4. gastroduodenal artery (GDA) encasement up to the hepatic artery (HA) with either short segment encasement or direct abutment of HA, without extension to the celiac axis (CA); and 5. tumor abutment of the SMA not to exceed 180° of the circumference. Unresectable tumors are those that have: 1. Arterial: Head/uncinate process: * Solid tumor contact with SMA \>180° * Solid tumor contact with the CA \>180° Body and tail: * Solid tumor contact of \>180° with the SMA or CA * Solid tumor contact with the CA and aortic involvement 2. Venous Head/uncinate process: * Unreconstructible SMV/PV due to tumor involvement or occlusion (can be due to tumor or bland thrombus) * Contact with most proximal draining jejunal branch into SMV Body and tail: • Unreconstructible SMV/PV due to tumor involvement or occlusion (can be due to tumor or bland thrombus) 4. Subjects have an ECOG performance status ≤ 1 5. Subjects who are eligible and able to participate in the study and accept to enter the study by signing written informed consent forms 6. Patients are recovered from toxicities from prior systemic therapies to CTCAE grade 0 or 1 (alopecia ≤ Grade 2 can enroll) and have adequate hematopoietic, liver and renal function at screening and before using study medication * Haemoglobin ≥ 8 g/dL * Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 * Absolute lymphocyte count ≥ 1000/mm3, * Platelets ≥ 100,000 /mm3 * Total white blood cell (WBC) ≥ 3,000 cells /mm3 * Coagulation tests (prothrombin time \[PT\], activated partial thromboplastin time \[APTT\], International Normalized Ratio \[INR\]) \< 1.5×ULN, * Total bilirubin ≤ 1.5×ULN, * Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase(SGOT) or …

Enrollment: 30 participants (estimated).