Neoplasms

All Conditions

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Gastrointestinal Agents

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Pancrelipase

Pancreatin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

In the safety run-in part, participants will receive a combination of NIS793, gemcitabine and nab-paclitaxel.

Participants will receive a combination of NIS793, gemcitabine and nab-paclitaxel

Note: As of 07-Jul-2023, treatment with NIS793/placebo was stopped.

Participants will receive a combination of placebo, gemcitabine and nab-paclitaxel

Note: As of 07-Jul-2023, treatment with NIS793/placebo was stopped.

Concentrate for solution infusion (Liquid in Vial)

NIS793

Nab-paclitaxel

Dextrose 5% in water (D5W) solution for infusion

Placebo

Novartis Pharmaceuticals

The purpose of this study is to evaluate the efficacy and safety of NIS793 in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel and placebo in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC).

This study aims to explore whether blockade of Transforming Growth Factor β (TGFβ) in combination with gemcitabine/nab-paclitaxel can reduce fibrosis in PDAC, restore chemo-sensitivity and ultimately lead to improvements in overall survival (OS) and other clinically relevant outcomes.

This is a randomized, double-blind, multicenter two-arm, phase III study that has two parts:

* Safety run-in part: An open-label safety run-in part will be conducted to confirm recommended phase 3 dose (RP3D) of NIS793 in combination with gemcitabine and nab-paclitaxel. Up to approximately 10 participants will be enrolled at each dose level to achieve at least 6 evaluable participants; however, if the starting dose is not recommended and a lower dose level is tested, 10 additional participants will be enrolled. The decision to open the randomized part will be based on dose confirmation and available safety, relevant PK, and other relevant data from run-in part
* Randomized part: Enrolled participants will be randomized to the two treatment arms.

The study treatment will be administered as a 28-day treatment cycle. Participants will be treated until unacceptable toxicity, disease progression per RECIST 1.1, withdrawal of consent or any other condition of treatment discontinuation specified in the protocol.

Note: As of 07-Jul-2023, treatment with NIS793/placebo was stopped. The trial was unblinded and study participants were allowed to continue with standard of care (SoC) chemotherapy (gemcitabine+ nab-paclitaxel) per investigator assessment.

Study of Efficacy and Safety of NIS793 in Combination With Standard of Care (SOC) Chemotherapy in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) - daNIS-2

A Randomized, Double-blind, Phase III Study, Comparing NIS793 in Combination With Gemcitabine and Nab-paclitaxel Versus (vs.) Placebo Combined With Gemcitabine and Nab-paclitaxel for First Line Treatment of Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) - daNIS-2

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Percentage of participants with DLTs during the first cycle of treatment in the safety run-in part. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness or concomitant medication that occurs within the first cycle of treatment with NIS793 in combination with gemcitabine and nab-paclitaxel

OS is defined as the time from date of randomization to date of death due to any cause.

Percentage of participants with AEs including changes in laboratory parameters, vital signs, body weight and cardiac assessments

Tolerability measured by the percentage of participants who have dose adjustments (interruptions or reductions) of NIS793

Tolerability measured by the dose intensity of NIS793. Dose intensity will be computed as the ratio of actual cumulative dose received and actual duration of exposure

PFS defined as the time from the date of enrollment (run-in part) or randomization (randomized part) to the date of the first documented progression based on investigator assessment and according to RECIST 1.1 or death due to any cause.

ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR), as per investigator assessment and according to RECIST 1.1

DCR is the proportion of participants with BOR of CR or PR or stable disease (SD) as per investigator assessment and according to RECIST 1.1

TTR is defined as the duration of time between the date of enrollment (run-in part) or randomization (randomized part) and the date of first documented response of either CR or PR.

OS is defined as the time from the date of enrollment to date of death due to any cause.

Blood samples will be collected for analysis of Cmax of NIS793

Blood samples will be collected for analysis of Ctrough of NIS793

Blood samples will be collected for analysis of AUClast of NIS793

Blood samples will be collected for analysis of AUCtau of NIS793

Blood samples will be collected for analysis of Tmax of NIS793

Blood samples will be collected for analysis of NIS793 serum concentration

ADA (anti-NIS793) prevalence at baseline is defined as the proportion of participants who have an ADA positive result at baseline

ADA (anti-NIS793) incidence on treatment is defined as the proportion of participants who are treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)

Spots Global Cancer Trial Database for metastatic pancreatic ductal adenocarcinoma (mpdac)