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

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

Study Overview

• Status: Completed
• Conditions: Metastatic Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Drug: NIS793; Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Placebo

Detailed Description

This was a randomized, double-blind, multicenter, two- group, phase III study that consisted of two parts: a Safety Run-in part and a Randomized part.

The decision to open the randomized part of the study was based on dose confirmation and available safety, relevant PK, and other clinical and laboratory data from the Safety Run-in part.

The open-label Safety Run-in part was conducted to confirm the recommended phase 3 dose (RP3D) of NIS793 in combination with gemcitabine and nab-paclitaxel. The safety run-in part started with one treatment regimen - NIS793 (2100 mg intravenous (i.v.) every 2 weeks (Q2W)) in combination with gemcitabine and nab-paclitaxel during the DLT assessment period. Dose limiting toxicity assessment period is defined as first cycle (i.e. 28 days, or 4 weeks) of dosing of the study treatment.

The Randomized part randomized participants 1:1 to one of the two treatment groups:

• Investigational group (Arm A); combination of NIS793, gemcitabine and nab-paclitaxel
• Control group (Arm B): combination of placebo, gemcitabine and nab-paclitaxel

Participants were stratified at randomization by Eastern Cooperative Oncology Group Performance Status (ECOG-PS) (0 or 1), presence of liver metastasis (yes vs. no), and region (North America, Europe and Australia vs. other countries).

Cross-over to the other treatment group was not allowed during the study duration.

The study treatment was administered as a 28-day treatment cycle. NIS793 was administered at a flat dose as confirmed in the Safety Run-in part on day 1 and 15 (e.g., 2100 mg i.v. Q2W or 2100 mg i.v. Q4W, if Q2W was considered as not tolerable in Safety Run-in part). Gemcitabine (1000 mg/m² on days 1, 8 and 15) and nab-paclitaxel (125 mg/m² on days 1, 8 and 15) were administered as per label.

As of 7-Jul-2023, the administration of NIS793/placebo was stopped for all participants following the recommendation from Data Monitoring Committee (DMC). Following the recommendation to stop administration of NIS793/placebo, the DMC encouraged to continue administration of gemcitabine/nab-paclitaxel to all participants per investigator's assessment, and the collection of additional follow-up data to better characterize the safety of NIS793 in combination with gemcitabine/nab-paclitaxel.

The study was considered complete when each participant completed at least 12 months of follow-up from randomization date, died, withdrew consent, or was lost to follow-up, whichever occurred first or, in the event of an early study termination. At which time, any study participant continuing with standard of care chemotherapy (gemcitabine + nab-paclitaxel) was transitioned off the study.

• Study Type: Interventional
• Enrollment (Actual): 511
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Novartis Investigative Site
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Novartis Investigative Site
• Belgium
  • Bonheiden, Belgium, 2820
    • Novartis Investigative Site
  • Brussels, Belgium, 1200
    • Novartis Investigative Site
  • Edegem, Belgium, 2650
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• Brazil
  • Federal District
    • Brasília, Federal District, Brazil, 70200-730
      • Novartis Investigative Site
  • Rio Grande do Sul
    • Ijuí, Rio Grande do Sul, Brazil, 98700-000
      • Novartis Investigative Site
    • Porto Alegre, Rio Grande do Sul, Brazil, 90560-032
      • Novartis Investigative Site
  • São Paulo
    • São Paulo, São Paulo, Brazil, 04014-002
      • Novartis Investigative Site
• Canada
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • Novartis Investigative Site
    • Cambridge, Ontario, Canada, N1R 3G2
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Novartis Investigative Site
• China
  • Beijing, China, 100730
    • Novartis Investigative Site
  • Beijing, China, 100021
    • Novartis Investigative Site
  • Beijing, China, 100036
    • Novartis Investigative Site
  • Shanghai, China, 200032
    • Novartis Investigative Site
  • Shanghai, China, 200127
    • Novartis Investigative Site
  • Shanghai, China, 200433
    • Novartis Investigative Site
  • Shanghai, China, 200025
    • Novartis Investigative Site
  • Tianjin, China, 300480
    • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Novartis Investigative Site
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Novartis Investigative Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Novartis Investigative Site
  • Liaoning
    • Dalian, Liaoning, China, 116001
      • Novartis Investigative Site
  • Shandong
    • Jining, Shandong, China, 272000
      • Novartis Investigative Site
  • Shanxi
    • Xian, Shanxi, China, 710061
      • Novartis Investigative Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Novartis Investigative Site
• Czechia
  • Brno, Czechia, 656 53
    • Novartis Investigative Site
  • Hradec Králové, Czechia, 500 05
    • Novartis Investigative Site
  • Nový Jičín, Czechia, 741 01
    • Novartis Investigative Site
  • Prague, Czechia, 140 59
    • Novartis Investigative Site
• Finland
  • Helsinki, Finland, 00290
    • Novartis Investigative Site
  • Tampere, Finland, FIN-33521
    • Novartis Investigative Site
• France
  • Avignon, France, 84082
    • Novartis Investigative Site
  • Besançon, France, 25030
    • Novartis Investigative Site
  • Créteil, France, 94010
    • Novartis Investigative Site
  • Lyon 08, France, 69373
    • Novartis Investigative Site
  • Marseille, France, 13273
    • Novartis Investigative Site
  • Montpellier, France, 34295
    • Novartis Investigative Site
  • Nantes, France, 44093
    • Novartis Investigative Site
  • Paris, France, 75015
    • Novartis Investigative Site
  • Alpes Maritimes
    • Nice, Alpes Maritimes, France, 06189
      • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Bochum, Germany, 44791
    • Novartis Investigative Site
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Hamburg, Germany, 20249
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60488
      • Novartis Investigative Site
  • Saxony-Anhalt
    • Halle, Saxony-Anhalt, Germany, 06120
      • Novartis Investigative Site
• Greece
  • Thessaloniki, Greece, 540 07
    • Novartis Investigative Site
  • Thessaloniki, Greece, 570 01
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, H 1122
    • Novartis Investigative Site
  • Budapest, Hungary, H-1097
    • Novartis Investigative Site
  • Hajdu Bihar Megye
    • Debrecen, Hajdu Bihar Megye, Hungary, 4032
      • Novartis Investigative Site
• Israel
  • Jerusalem, Israel, 9112001
    • Novartis Investigative Site
  • Ramat Gan, Israel, 5265601
    • Novartis Investigative Site
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • FI
    • Florence, FI, Italy, 50134
      • Novartis Investigative Site
  • MI
    • Milan, MI, Italy, 20133
      • Novartis Investigative Site
    • Milan, MI, Italy, 20162
      • Novartis Investigative Site
  • VR
    • Verona, VR, Italy, 37134
      • Novartis Investigative Site
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 4648681
      • Novartis Investigative Site
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • Novartis Investigative Site
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-8515
      • Novartis Investigative Site
  • Osaka
    • Osaka, Osaka, Japan, 5418567
      • Novartis Investigative Site
  • Tokyo
    • Chuo Ku, Tokyo, Japan, 1040045
      • Novartis Investigative Site
    • Koto Ku, Tokyo, Japan, 1358550
      • Novartis Investigative Site
• Netherlands
  • Utrecht, Netherlands, 3543 AZ
    • Novartis Investigative Site
• Norway
  • Oslo, Norway, NO-0407
    • Novartis Investigative Site
  • Oslo
    • Nordbyhagen, Oslo, Norway, 1478
      • Novartis Investigative Site
• Russia
  • Omsk, Russia, 644013
    • Novartis Investigative Site
  • Saint Petersburg, Russia, 196603
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 168583
    • Novartis Investigative Site
• Slovakia
  • Banská Bystrica, Slovakia, 975 17
    • Novartis Investigative Site
  • Bratislava, Slovakia, 83310
    • Novartis Investigative Site
  • Košice, Slovakia, 041 91
    • Novartis Investigative Site
• South Korea
  • Seoul, South Korea, 03080
    • Novartis Investigative Site
  • Seoul, South Korea, 05505
    • Novartis Investigative Site
  • Seoul, South Korea, 06591
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08035
    • Novartis Investigative Site
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Madrid, Spain, 28009
    • Novartis Investigative Site
  • A Coruna
    • Santiago Compostela, A Coruna, Spain, 15706
      • Novartis Investigative Site
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Novartis Investigative Site
• Sweden
  • Malmö, Sweden, SE-205 02
    • Novartis Investigative Site
  • Umeå, Sweden, 901 85
    • Novartis Investigative Site
• Switzerland
  • Bellinzona, Switzerland, 6500
    • Novartis Investigative Site
  • Geneva, Switzerland, 1211
    • Novartis Investigative Site
  • Sankt Gallen, Switzerland, 9007
    • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taipei, Taiwan, 11217
    • Novartis Investigative Site
  • Taoyuan, Taiwan, 33305
    • Novartis Investigative Site
• Turkey (Türkiye)
  • Izmir, Turkey (Türkiye), 35100
    • Novartis Investigative Site
  • Kadikoy
    • Istanbul, Kadikoy, Turkey (Türkiye), 34722
      • Novartis Investigative Site
  • Sihhiye-Altindag
    • Ankara, Sihhiye-Altindag, Turkey (Türkiye), 06230
      • Novartis Investigative Site
  • Yuregir
    • Adana, Yuregir, Turkey (Türkiye), 01250
      • Novartis Investigative Site
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Novartis Investigative Site
  • Liverpool, United Kingdom, CH63 4JY
    • Novartis Investigative Site
  • London, United Kingdom, EC1A 7BE
    • Novartis Investigative Site
  • Oxford, United Kingdom, OX3 7LE
    • Novartis Investigative Site
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Novartis Investigative Site
• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
  • California
    • Los Angeles, California, United States, 90095
      • University of California LA
  • Florida
    • Orlando, Florida, United States, 32804
      • AdventHealth
  • Indiana
    • Fort Wayne, Indiana, United States, 46815
      • Fort Wayne Medical Oncology Hematology Inc
  • New York
    • New York, New York, United States, 10016
      • NYU Clinical Cancer Center
  • Texas
    • Dallas, Texas, United States, 75204
      • US Oncology Research Dallas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

Applicable for both Safety run-in and Randomized part

• Participants aged ≥18 years with histologically or cytologically confirmed (based on local assessment and per local guidelines) mPDAC eligible for treatment in the first line setting and not amenable for potentially curative surgery
• Presence of at least one measurable lesion assessed by Computerized Tomography (CT) and/or Magnetic Resonance Imaging (MRI) according to RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Adequate organ function (assessed by central laboratory for eligibility)
• Participants must have recovered from treatment-related toxicities of prior anticancer therapies to grade ≤ 1 (CTCAE v 5.0) at time of screening, except alopecia.

Key Main Exclusion Criteria:

Applicable for both Safety run-in and Randomized part

• Previous systemic anti-cancer treatment for metastatic PDAC
• Pancreatic neuroendocrine (islet) or acinar tumors
• Participants with known status of microsatellite instability-high (MSI-H) or mismatch repair-deficient pancreatic cancer (if status is not already available, testing is not required at screening).
• Participant has not recovered from a major surgery performed prior to start of study treatment or has had a major surgery within 4 weeks prior to start of study treatment.
• Radiation therapy or brain radiotherapy ≤ 4 weeks prior to start of study treatment (palliative radiotherapy to bone lesions allowed > 2 weeks prior to start of study treatment).
• Impaired cardiac function or clinically significant cardio-vascular disease
• Use of hematopoietic growth factors or transfusion support ≤ 2 weeks prior to start of study treatment.
• Participant has conditions that are considered to have a high risk of clinically significant gastrointestinal tract bleeding or any other condition associated with or history of significant bleeding.
• Serious non-healing wounds.
• Pregnant or breast-feeding women
• Women of childbearing potential, unless willing to use highly effective contraception methods during treatment and after stopping study treatments as indicated
• Pre-existing peripheral neuropathy > grade 1 (CTCAE v5.0)

Other Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Safety run-in part: NIS793 plus (Gemcitabine and Nab-paclitaxel); Participants received a combination of NIS793, Gemcitabine and Nab-paclitaxel : NIS793 at 2100 mg (Days 1 and 15); Gemcitabine at 1000 mg/m² (Days 1, 8 and 15); Nab-paclitaxel at 125 mg/m² (Days 1, 8 and 15) Note: As of 7-Jul-2023, treatment with NIS793/placebo was stopped. Study participants were allowed to continue with standard of care (SoC) chemotherapy (gemcitabine+ nab-paclitaxel) per investigator assessment.	Drug: NIS793; Concentrate for solution infusion (Liquid in Vial); Drug: Nab-paclitaxel; Per locally approved formulation; Drug: Gemcitabine; Per locally approved formulation
Experimental: Randomized part (Arm A): NIS793 plus (Gemcitabine and Nab-paclitaxel); Participants received a combination of NIS793, gemcitabine and nab-paclitaxel: NIS793 at 2100 mg (Days 1 and 15) assuming this was the confirmed RP3D in the safety run-in part or NIS793 at 2100 mg on Day 1 if dose level -1 was the confirmed RP3D in the safety run-in; Gemcitabine at 1000 mg/m² (Days 1, 8 and 15); Nab-paclitaxel at 125 mg/m² (Days 1, 8 and 15) Note: As of 7-Jul-2023, treatment with NIS793/placebo was stopped. Study participants were allowed to continue with standard of care (SoC) chemotherapy (gemcitabine+ nab-paclitaxel) per investigator assessment.	Drug: NIS793; Concentrate for solution infusion (Liquid in Vial); Drug: Nab-paclitaxel; Per locally approved formulation; Drug: Gemcitabine; Per locally approved formulation; Drug: Placebo; Dextrose 5% in water (D5W) solution for infusion
Placebo Comparator: Randomized part (Arm B): Placebo plus (Gemcitabine and Nab-paclitaxel); Participants received a combination of placebo, gemcitabine and nab-paclitaxel: Placebo for NIS793 (Days 1 and 15); Gemcitabine at 1000 mg/m² (Days 1, 8 and 15); Nab-paclitaxel at 125 mg/m² (Days 1, 8 and 15) Note: As of 7-Jul-2023, treatment with NIS793/placebo was stopped. Study participants were allowed to continue with standard of care (SoC) chemotherapy (gemcitabine+ nab-paclitaxel) per investigator assessment.	Drug: Nab-paclitaxel; Per locally approved formulation; Drug: Gemcitabine; Per locally approved formulation; Drug: Placebo; Dextrose 5% in water (D5W) solution for infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety run-in Part: Percentage of Participants With Dose Limiting Toxicities (DLTs) During the First Cycle (4 Weeks) of Treatment.	A dose-limiting toxicity (DLT) was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first cycle (i.e., 28 days or 4 weeks) of the treatment with NIS793 in combination with gemcitabine/nab-paclitaxel. The National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 5 was used for all grading.	Up to 4 weeks
Randomized Part: Overall Survival (OS)	Overall Survival (OS) was defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last known date patient alive.	From randomization up to death, assessed up to approximately 34 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events (AEs)	An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product. Treatment emergent Adverse Event (TEAEs) in this study are events that started after the first dose of study treatment and until 30 days after last dose of SOC chemotherapies and up to 90 days after NIS793, whichever is later.	Up to approximately 32 months
Percentage of Participants With Dose Interruptions and Dose Reductions of NIS793 in Combination With Gemcitabine and Nab-paclitaxel	No dose reductions were allowed for NIS793 in the Randomized part and beyond the first 28 days period of the Safety Run-in part. Increasing the dosing interval from every 2 weeks (Q2W) to every 2 weeks (Q4W) was allowed. Dose interruption for NIS793 was permitted if adverse drug reaction was suspected to be related to NIS793. If NIS793 was interrupted or delayed for > 8 weeks due to toxicity that was suspected to be related to treatment, study treatment was permanently discontinued.	Up to approximately 32 months
Dose Intensity of NIS793 in Combination With Gemcitabine and Nab-paclitaxel	Dose intensity was computed as the ratio of actual cumulative dose received and actual duration of exposure.	Up to approximately 32 months
Progression-Free Survival (PFS)	Progression-Free Survival (PFS) was defined as the time from the enrollment (run-in part) or randomization (randomized part) to the date of the first documented disease progression based on local investigator assessment as per RECIST 1.1 or date of death due to any cause, whichever occurs first. PFS was censored if no PFS event was observed before the analysis cut-off date. The censoring date was the date of the last adequate tumor assessment prior to the analysis cut-off.	From enrollment (run-in part) or randomization (randomized part) up to disease progression or death, assessed up to approximately 34 months
Overall Response Rate (ORR)	Overall Response Rate (ORR) was defined as the proportion of participants with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) as per local review. ORR was evaluated according to RECIST 1.1. The BOR was determined from response assessments undertaken while on treatment.	Up to approximately 34 months
Disease Control Rate (DCR)	Disease Control Rate (DCR) was defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR), or Stable Disease (SD) or Non-CR/Non-progressive disease as per local review. DCR was evaluated according to RECIST 1.1.	Up to approximately 34 months
Duration of Response (DOR)	Duration of Response (DOR) was defined as the duration of time between the date of first documented response (CR or PR) and the date of first documented progression or death due to any cause.	Up to approximately 34 months
Time to Response (TTR)	Time to Response (TTR) was 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 as per local review, which was subsequently confirmed. TTR was evaluated according to RECIST 1.1. Participants without a confirmed CR or PR were censored at the time of PFS event (i.e., disease progression or death due to any cause) for participants with a PFS event (i.e., disease progression or death due to any cause), or at the date of the last adequate tumor assessment for participants without a PFS event.	From enrollment (run-in part) or randomization (randomized part) up to first documented response, assessed up to approximately 34 months
Safety run-in Part: Trough Concentration (Ctrough) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel	Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Ctrough was listed and summarized using descriptive statistics.	Cycles 1 and 3 Day 15 (0 hour (pre-dose)), Cycles 2, 4, 6 and 12 Day 1 (0 hour (pre-dose)). 1 cycle = 28 days.
Safety run-in Part: Maximum Concentration (Cmax) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel	Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Cmax was listed and summarized using descriptive statistics.	Cycles 1 and 3 Day 1: 0 hour (pre-dose) and 1 hour. 1 cycle = 28 days.
Safety run-in Part: Time to Reach Maximum Concentration (Tmax) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel	Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Tmax was listed and summarized using descriptive statistics.	Cycles 1 and 3 Day 1: 0 hour (pre-dose) and 1 hour. 1 cycle = 28 days.
Randomized Part (Chinese Participants With Intensive PK Sampling): Trough Concentration (Ctrough) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel	In the randomized part, participants enrolled for treatment in China were assigned to more intensive PK sampling (taken into account the ability of clinical sites to comply with the instructions in the laboratory manual concerning the preparation of serum samples) to assess PK of NIS793 in Chinese participants. Venous whole blood samples were collected for activity-based pharmacokinetics characterization and Ctrough was summarized using descriptive statistics.	Cycle 1 Day 15, Cycle 3 Day 1, Cycle 3 Day 15, Cycle 4 Day 1 and Cycle 6 Day 1: 0 hour (pre-dose). 1 cycle = 28 days.
Randomized Part (Chinese Participants With Intensive PK Sampling): Maximum Concentration (Cmax) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel	In the randomized part, participants enrolled for treatment in China were assigned to more intensive PK sampling (taken into account the ability of clinical sites to comply with the instructions in the laboratory manual concerning the preparation of serum samples) to assess PK of NIS793 in Chinese participants. Venous whole blood samples were collected for activity-based pharmacokinetics characterization and Cmax was summarized using descriptive statistics.	Cycles 1 and 3 Day 1: 0 hour (pre-dose) and 1 hour. 1 cycle = 28 days.
Randomized Part (Chinese Participants With Intensive PK Sampling): Time to Reach Maximum Concentration (Tmax) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel	In the randomized part, participants enrolled for treatment in China were assigned to more intensive PK sampling (taken into account the ability of clinical sites to comply with the instructions in the laboratory manual concerning the preparation of serum samples) to assess PK of NIS793 in Chinese participants. Venous whole blood samples were collected for activity-based pharmacokinetics characterization and Tmax was summarized using descriptive statistics.	Cycles 1 and 3 Day 1: 0 hour (pre-dose) and 1 hour. 1 cycle = 28 days.
Randomized Part (Chinese Participants With Intensive PK Sampling): Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel	In the randomized part, participants enrolled for treatment in China were assigned to more intensive PK sampling (taken into account the ability of clinical sites to comply with the instructions in the laboratory manual concerning the preparation of serum samples) to assess PK of NIS793 in Chinese participants. Venous whole blood samples were collected for activity-based pharmacokinetics characterization and AUClast was summarized using descriptive statistics.	Cycles 1 Day 1: 0 hour (pre-dose) and 1 hour. 1 cycle = 28 days.
Randomized Part (Chinese Participants With Intensive PK Sampling): Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel	In the randomized part, participants enrolled for treatment in China were assigned to more intensive PK sampling (taken into account the ability of clinical sites to comply with the instructions in the laboratory manual concerning the preparation of serum samples) to assess PK of NIS793 in Chinese participants. Venous whole blood samples were collected and AUCtau was summarized using descriptive statistics.	Cycles 3 Day 1: 0 hour (pre-dose) and 1 hour. 1 cycle = 28 days.
Randomized Part (Participants Without Intensive PK Sampling): Trough Concentration (Ctrough) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel	For participants without intensive PK sampling, venous whole blood samples were collected for activity-based pharmacokinetics characterization. Ctrough was listed and summarized using descriptive statistics.	Cycles 2, 3, 4, 6 and 12 Day 1 (0 hour (pre-dose)). 1 cycle = 28 days.
Randomized Part (Participants Without Intensive PK Sampling): Maximum Concentration (Cmax) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel	For Chinese participants without intensive PK sampling schedule and global participants in the randomized part, for which only sparse PK samples were collected for activity-based pharmacokinetics characterization, Cmax was listed and summarized using descriptive statistics.	Cycles 1 and 3: Day 1 (0 hour (pre-dose)). 1 cycle = 28 days.
Randomized Part (Participants Without Intensive PK Sampling): Time to Reach Maximum Concentration (Tmax) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel	For Chinese participants without intensive PK sampling schedule and global participants in the randomized part, for which only sparse PK samples were collected for activity-based pharmacokinetics characterization, Tmax was listed and summarized using descriptive statistics.	Cycles 1 and 3: Day 1 (0 hour (pre-dose)). 1 cycle = 28 days.
Randomized Part: Anti-drug Antibodies (ADA) Against NIS793 Prevalence at Baseline	Anti-drug antibodies (ADA) against NIS793 prevalence at baseline refers to the proportion of subjects who have developed antibodies against the drug NIS793 before starting treatment. This is calculated by dividing the number of subjects with ADA-positive samples at baseline by the total number of subjects whose baseline samples were tested for ADA.	Baseline
Randomized Part: Anti-drug Antibodies (ADA) Against NIS793 Incidence on Treatment	Anti-drug antibodies (ADA) against NIS793 incidence on treatment refers to the proportion of participants who developed antibodies against the drug NIS793 during the treatment period. This can be categorized into two types: Treatment-induced ADA positive: Participants who were ADA-negative at baseline but became ADA-positive after starting the treatment.; Treatment-boosted ADA positive: Participants who were ADA-positive at baseline and showed a significant increase in ADA titer during the treatment.	From date of first study drug intake up to approximately 34 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2021
• Primary Completion (Actual): August 13, 2024
• Study Completion (Actual): August 13, 2024

Study Registration Dates

• First Submitted: June 21, 2021
• First Submitted That Met QC Criteria: June 21, 2021
• First Posted (Actual): June 23, 2021

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Gemcitabine; Pancreas; Abraxane; Nab-paclitaxel; mPDAC; NIS793; metastatic pancreatic ductal adenocarcinoma (mPDAC)
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Gemcitabine; 130-nm albumin-bound paclitaxel; NIS-793
• Other Study ID Numbers: CNIS793B12301; 2021-000591-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No