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Pancrelipase

Pancreatin

Phase 0 - subjects diagnosed with an operable adenocarcinoma of the pancreas will have 8 siG12D LODER placed in tumor. The siG12D LODER will be placed in the subject's tumor using an EUS biopsy needle.

Phase I - subjects diagnosed with locally non-operable advanced adenocarcinoma of the pancreas. These subjects will have one of three different siG12D LODERs dose levels placed in tumor - Either 1 siG12D LODER, 2 siG12D LODERs or 8 siG12D LODERs. The siG12D LODER/s will be placed in the subject's tumor using an EUS biopsy needle.

siG12D LODER

Ayala Hubert, MD

Talya Golan, MD

Amiel Segal, MD

Phase 0 - Open label, Single dose study of siG12D LODER in Patients with operable adenocarcinoma of the pancreas.

The primary endpoint:

To assess efficacy and local distribution of siRNA out of eight high dose siG12D LODERs in patients diagnosed with operable adenocarcinoma of the pancreas.

The Secondary endpoint:

Short term tolerability and safety assessment

Phase I - This study is designed to investigate the safety of siG12D LODER (Local Drug EluteR) in patients diagnosed with adenocarcinoma of the pancreas.

The primary endpoint:

To asses efficacy of siG12D LODER and local distribution in non-operable patients by histopathology measurements, local distribution by RNA analysis.

To define the dose-limiting toxicities (DLT)

The Secondary endpoint

1. To determine the recommended Phase II dose (RP2D)
2. To define and maximum tolerated dose (MTD)
3. In the event of surgery, assessment of siG12D LODER local distribution and efficacy will be based on histopathology measurements and RNA analysis.
4. Progression free survival - only by long term follow-up

The investigational agent siG12D LODER (Local Drug EluteR) is a miniature biodegradable polymeric matrix that encompasses anti KRASG12D siRNA (siG12D) drug, designed to release the drug regionally within a pancreatic tumor, at a prolonged rate of 12-16 weeks.

The majority of pancreatic ductal adenocarcinomas involve mutations in the KRAS oncogene (the most common is G12D), therefore stable administration of KRASG12D siRNA has the potential to silence and lead to apoptosis of such cancer cells and thereby slow and even halt the tumor growth.

Phase I - Escalating Dose Study of siG12D LODER (Local Drug EluteR) in Patients With Locally Advanced Adenocarcinoma of the Pancreas, and a Single Dose Study of siG12D LODER (Local Drug EluteR) in Patients With Non-operable Adenocarcinoma of the Pancreas

Silenseed Ltd

Antineoplastic Agents

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Folfirinox

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Eight siG12D-LODER+Gemcitabine+nab-Paclitaxel or Eight siG12D-LODER+Folfirinox or Eight siG12D-LODER+modifide Folfirinox

The implantation of siG12D-LODERs is selected to meet current gastroenterology endoscopic ultrasound (EUS) biopsy procedures, proved to be highly effective and safe.

siG12D-LODER

Gemcitabine+nab-Paclitaxel

Orit Pollack-Shragai, MSc, MBA

Celina Ang, MD

Christopher DiMaio, MD

Christopher J DiMaio, MD

Eileen M O'Reilly, MD

Anna M Varghese, MD

Eileen M. O'Reilly, MD

Mark A Schattner, MD

Milind Javle, MD

Manoop Bhutani, MD

Valerya Semenysty, MD

Iyad Khamaysi, MD

Talia Golan, MD

Maor Lahav, MD

Ravit Geva, M.D

Adam Phillips, M.D

In this Phase II study a dose of 2.8 mg (eight 0.35 mg siG12D-LODERs) will be administered in 12-week cycles to patients with unresectable or borderline resectable locally advanced pancreatic cancer combined with chemotherapy treatment.

Primary Outcome:

- ORR at 6 months.

In this Phase II study a dose of 2.8 mg (eight 0.35 mg siG12D-LODERs) will be administered in 12-week cycles to patients with unresectable or borderline resectable LAPC combined with chemotherapy treatment (Gemcitabine+nab-Paclitaxel or Folfirinox or modified Folfirinox). This will be a study to assess the response rate of the siG12D-LODER in patients with unresectable or borderline resectable LAPC. The study is of a single arm design with one arm receiving siG12D-LODER + chemotherapy.

The investigational agent siG12D-LODER is a miniature biodegradable bio polymeric matrix that encompasses the drug, designed and produced by Silenseed Ltd. The implantation of LODERs is selected to meet current gastroenterology endoscopic ultrasound (EUS) biopsy procedures, proved to be highly effective and safe.

siG12D-LODER has been studied in the escalating dose Phase I study of 15 patients, and results showed high safety and tolerability profiles, with no single DLT.

A Phase 2 Study of siG12D LODER in Combination With Chemotherapy in Patients With Locally Advanced Pancreatic Cancer

A Prospective, Multinational, Multi-Center, Phase 2, Single-Arm, Open-Label Study Evaluating the Efficacy, Safety and Tolerability of siG12D-LODER in Combination With Standard of Care Chemotherapy in the Treatment of Patients With Locally Advanced Pancreatic Cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Phase I - Escalating Dose Study of siG12D LODER (Local Drug EluteR) in Patients With Locally Advanced Adenocarcinoma of the Pancreas, and a Single Dose Study of siG12D LODER (Local Drug EluteR) in Patients With Non-operable Adenocarcinoma of the Pancreas	NCT01188785	Pancreatic Duct... Pancreatic Canc...	siG12D LODER	18 Years -	Silenseed Ltd
A Phase 2 Study of siG12D LODER in Combination With Chemotherapy in Patients With Locally Advanced Pancreatic Cancer	NCT01676259	Pancreatic Duct... Pancreatic Canc...	siG12D-LODER Gemcitabine+nab... Folfirinox	18 Years -	Silenseed Ltd

Spots Global Cancer Trial Database for non operable pancreatic ductal adenocarcinoma