Evaluation of Overall Survival in Metastatic Pancreatic Ductal Adenocarcinoma with SBP-101, Nab-Paclitaxel, and Gemcitabine Therapy

The primary objective of this study is to compare **overall survival** (OS) between subjects receiving **SBP-101** and those receiving a placebo, in combination with **nab-paclitaxel** and **gemcitabine**, in patients with **metastatic pancreatic ductal adenocarcinoma**. This objective is clinically relevant as it aims to determine the potential survival benefit of SBP-101, which could lead to improved treatment outcomes for this aggressive cancer type.

Secondary objectives include:

• Comparing **progression-free survival** (PFS) between SBP-101 and placebo.
• Comparing **objective response rate** (ORR) between SBP-101 and placebo.
• Comparing **disease control rate** (DCR) between SBP-101 and placebo.
• Comparing **duration of response** (DoR) between SBP-101 and placebo.
• Comparing changes in **quality of life** (QOL) scores between SBP-101 and placebo.
• Comparing the **safety and tolerability** of SBP-101 compared to placebo when administered with nab-paclitaxel and gemcitabine.
• Exploratory: Comparing the effects of SBP-101 and placebo on blood levels of **CA19-9** and **circulating tumor DNA** (cT DNA).

The clinical trial involves a total of **140 participants** diagnosed with **Metastatic Pancreatic Ductal Adenocarcinoma**. The study population includes both male and female adults aged 18 years and older. Participants were selected based on specific inclusion criteria, including a histological or cytological confirmation of the disease, a diagnosis of metastatic disease within the past three months, and an expectation to receive standard treatment with gemcitabine and nab-paclitaxel. All participants are required to have a life expectancy of at least three months and adequate bone marrow, hepatic, renal, and coagulation function. The trial does not include a vulnerable population, and both genders are represented. Participants must also meet specific health criteria, such as a QTc interval of ≤ 470 ms for women and ≤ 450 ms for men on the ECG baseline. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the efficacy of SBP-101 in combination with nab-paclitaxel and gemcitabine in subjects with **metastatic pancreatic ductal adenocarcinoma**. The primary objective is to compare overall survival (OS) between subjects receiving SBP-101 and those receiving a placebo. The trial is expected to run from March 2022 to February 2025, with a maximum treatment period of 99 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically confirmed metastatic pancreatic ductal adenocarcinoma, life expectancy of at least three months, and adequate organ function. Following successful screening, participants will be randomized to receive either SBP-101 or placebo, in addition to standard treatment with nab-paclitaxel and gemcitabine. The study drug will be administered via **subcutaneous injection**, while nab-paclitaxel and gemcitabine will be given through **intravenous infusion**.

Throughout the trial, participants will attend regular follow-up visits to monitor treatment response and safety. These visits will include assessments of progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), duration of response (DoR), and quality of life (QoL) using standardized questionnaires. The end-of-study visit will occur after the completion of the treatment period or upon early termination.

Participant involvement is expected to last up to 99 weeks, depending on individual response and tolerance to the treatment. Conditions that may lead to early termination from the study include disease progression, unacceptable toxicity, withdrawal of consent, or any other reason deemed necessary by the investigator. The trial will adhere to rigorous ethical standards, ensuring that all participants provide informed consent prior to enrollment.

The clinical trial involves the administration of **SBP-101**, an experimental medication with the active substance **ivospemin**. SBP-101 is formulated as an injection and is administered via subcutaneous injection. The dosage is calculated based on body weight, with a maximum daily dose of 0.27 mg/kg and a total maximum dose of 4.32 mg/kg over the treatment period. The treatment duration is set for a maximum of 99 days. SBP-101 functions as a small molecule, polyamine metabolic inhibitor, and is not a pediatric formulation. Participant compliance with the dosing schedule will be monitored throughout the trial.

The study also includes a **placebo** control, which is a relabeled form of **sodium hydrogen carbonate PHEUR**. This placebo is administered via subcutaneous injection, similar to the experimental treatment, to maintain blinding. The placebo does not have an active therapeutic effect and is used to compare the efficacy of SBP-101. The placebo is also not a pediatric formulation and is administered over the same maximum treatment period of 99 days.

In addition to the experimental and placebo treatments, the trial incorporates standard-of-care therapies, including **Abraxane** and **Gemcitabin Hikma**. Abraxane, containing the active substance **paclitaxel albumin-bound**, is provided as a powder for dispersion for infusion. It is administered via intravenous infusion with a maximum daily dose of 125 mg/m² and a total maximum dose of 1500 mg/m² over the treatment period. Gemcitabin Hikma, with the active substance **gemcitabine**, is supplied as a solution for infusion and is also administered intravenously. The maximum daily dose for Gemcitabin Hikma is 1000 mg/m², with a total maximum dose of 12000 mg/m². Both Abraxane and Gemcitabin Hikma are cytostatic drugs and are relabeled for clinical trial distribution. The administration of these drugs follows a similar 99-day treatment period, and participant adherence to the dosing regimen is closely monitored.

Efficacy in the clinical trial will be assessed primarily through the measurement of **overall survival (OS)**, which is defined as the time from Study Day 1, the date of the first dose of study drug treatment, until death from any cause. This primary endpoint will provide a direct measure of the treatment's impact on survival in subjects with metastatic pancreatic ductal adenocarcinoma.

Secondary efficacy endpoints include **progression-free survival (PFS)**, which is the time until disease progression or death from any cause, whichever occurs first. Additionally, the **objective response rate (ORR)** will be evaluated, defined as the percentage of subjects with a best overall response of complete response (CR) or partial response (PR), determined using RECIST 1.1 criteria. The **disease control rate (DCR)** will also be assessed, defined as the percentage of subjects with confirmed CR, PR, or stable disease (SD) for at least 16 weeks. Furthermore, the **duration of response (DoR)** in subjects who achieve a CR or PR will be measured, defined as the time from the onset of the first CR or PR until disease progression or death from any cause. Quality of life (QoL) will be assessed using the EORTC QLQ-30 and QLQ-PAN26 questionnaires, providing insights into the impact of the treatment on patients' well-being.