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

NCT04935359 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: CNIS793B123012021-000591-10
• Study Type: interventional
• Target: 511
• Locations: 27 countries
• Sites: 113

Brief Summary

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.

Conditions

Metastatic Pancreatic Ductal Adenocarcinoma

Keywords

mPDAC; NIS793; Pancreas; metastatic pancreatic ductal adenocarcinoma (mPDAC); Nab-paclitaxel; Abraxane; Gemcitabine

Outcome Measures

Primary Outcomes (2)

• Safety run-in part: Percentage of participants with dose limiting toxicities (DLTs) during the first cycle (4 weeks) of treatment.

  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

  Up to 4 weeks

• Randomized part: Overall survival (OS)

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

  From randomization up to death, assessed up to approximately 19 months

Secondary Outcomes (16)

• Percentage of participants with Adverse Events (AEs)

  Up to approximately 19 months

• Percentage of participants with dose interruptions and dose reductions of NIS793 in combination with gemcitabine and nab-paclitaxel

  Up to approximately 19 months

• Dose intensity of NIS793 in combination with gemcitabine and nab-paclitaxel

  Up to approximately 19 months

• Progression-free survival (PFS) by investigator assessment per RECIST 1.1

  From enrollment (run-in part) or randomization (randomized part) up to disease progression or death, assessed up to approximately 19 months

• Overall response rate (ORR) by investigator assessment per RECIST 1.1

  Up to approximately 19 months

Study Arms (3)

Safety run-in part: NIS793+gemcitabine+nab-paclitaxel

EXPERIMENTAL

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

Drug: NIS793; Drug: Nab-paclitaxel; Drug: Gemcitabine

Randomized part: NIS793+gemcitabine+nab-paclitaxel

EXPERIMENTAL

Participants will receive a combination of NIS793, gemcitabine and nab-paclitaxel Note: As of 07-Jul-2023, treatment with NIS793/placebo was stopped.

Drug: NIS793; Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Placebo

Randomized part: placebo+gemcitabine+nab-paclitaxel

PLACEBO COMPARATOR

Participants will receive a combination of placebo, gemcitabine and nab-paclitaxel Note: As of 07-Jul-2023, treatment with NIS793/placebo was stopped.

Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Placebo

Interventions

NIS793 DRUG

Concentrate for solution infusion (Liquid in Vial)

Randomized part: NIS793+gemcitabine+nab-paclitaxel; Safety run-in part: NIS793+gemcitabine+nab-paclitaxel

Nab-paclitaxel DRUG

Per locally approved formulation

Randomized part: NIS793+gemcitabine+nab-paclitaxel; Randomized part: placebo+gemcitabine+nab-paclitaxel; Safety run-in part: NIS793+gemcitabine+nab-paclitaxel

Gemcitabine DRUG

Per locally approved formulation

Randomized part: NIS793+gemcitabine+nab-paclitaxel; Randomized part: placebo+gemcitabine+nab-paclitaxel; Safety run-in part: NIS793+gemcitabine+nab-paclitaxel

Placebo DRUG

Dextrose 5% in water (D5W) solution for infusion

Randomized part: NIS793+gemcitabine+nab-paclitaxel; Randomized part: placebo+gemcitabine+nab-paclitaxel

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (113)

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

University of California LA

Los Angeles, California, 90095, United States

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Advent Health Cancer Institute

Orlando, Florida, 32804, United States

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Fort Wayne Medical Oncology Hematology Inc

Fort Wayne, Indiana, 46815, United States

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NYU Clinical Cancer Center

New York, New York, 10016, United States

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US Oncology Research Dallas

Dallas, Texas, 75204, United States

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Houston Methodist Hospital

Houston, Texas, 77030, United States

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Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

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Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

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Novartis Investigative Site

Adelaide, South Australia, 5000, Australia

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Novartis Investigative Site

Perth, Western Australia, 6009, Australia

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Novartis Investigative Site

Bonheiden, 2820, Belgium

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Brussels, 1200, Belgium

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Edegem, 2650, Belgium

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Leuven, 3000, Belgium

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Brasília, Federal District, 70200-730, Brazil

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Ijuí, Rio Grande do Sul, 98700-000, Brazil

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Porto Alegre, Rio Grande do Sul, 90035-001, Brazil

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São Paulo, São Paulo, 04014-002, Brazil

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Brampton, Ontario, L6R 3J7, Canada

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Cambridge, Ontario, N1R 3G2, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Guangzhou, Guangdong, 510000, China

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Harbin, Heilongjiang, 150081, China

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Nanjing, Jiangsu, 210029, China

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Dalian, Liaoning, 116001, China

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Jining, Shandong, 272000, China

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Xian, Shanxi, 710061, China

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Chengdu, Sichuan, 610041, China

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Hangzhou, Zhejiang, 310022, China

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Beijing, 100021, China

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Beijing, 100036, China

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Beijing, 100730, China

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Shanghai, 200025, China

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Shanghai, 200032, China

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Shanghai, 200127, China

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Shanghai, 200433, China

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Tianjin, 300480, China

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Brno, Czech Republic, 656 53, Czechia

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Nový Jičín, Czech Republic, 74101, Czechia

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Hradec Králové, CZE, 500 05, Czechia

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Prague, 140 59, Czechia

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Helsinki, 00290, Finland

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Tampere, FIN-33521, Finland

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Nice, Alpes Maritimes, 06189, France

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Avignon, 84082, France

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Besançon, 25030, France

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Créteil, 94010, France

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Lyon 08, 69373, France

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Marseille, 13273, France

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Montpellier, 34295, France

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Nantes, 44093, France

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Paris, 75015, France

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Berlin, 13353, Germany

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Bochum, 44791, Germany

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Essen, 45147, Germany

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Frankfurt, 60488, Germany

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Halle S, 06120, Germany

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Hamburg, 20249, Germany

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Ulm, 89081, Germany

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Thessaloniki, 540 07, Greece

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Thessaloniki, 57001, Greece

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Budapest, H 1122, Hungary

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Budapest, H-1097, Hungary

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Debrecen, 4032, Hungary

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Jerusalem, 9112001, Israel

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Ramat Gan, 52621, Israel

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Tel Aviv, 6423906, Israel

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Florence, FI, 50134, Italy

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Milan, MI, 20133, Italy

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Milan, MI, 20162, Italy

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Verona, VR, 37126, Italy

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Nagoya, Aichi-ken, 464 8681, Japan

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Kashiwa, Chiba, 277 8577, Japan

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Yokohama, Kanagawa, 241-8515, Japan

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Osaka, Osaka, 541-8567, Japan

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Chuo Ku, Tokyo, 104 0045, Japan

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Koto Ku, Tokyo, 135 8550, Japan

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Novartis Investigative Site

Utrecht, 3543 AZ, Netherlands

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Nordbyhagen, Oslo County, 1478, Norway

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Oslo, NO-0407, Norway

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Omsk, 644013, Russia

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Pushkin Saint Petersburg, 196603, Russia

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Singapore, 168583, Singapore

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Bratislava, Slovak Republic, 83310, Slovakia

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Banská Bystrica, 975 17, Slovakia

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Košice, 041 91, Slovakia

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Seoul, Seocho Gu, 06591, South Korea

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Novartis Investigative Site

Seoul, 03080, South Korea

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Novartis Investigative Site

Seoul, 05505, South Korea

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Barcelona, Catalonia, 08035, Spain

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Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

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Novartis Investigative Site

Santiago de Compostela, Galicia, 15706, Spain

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Novartis Investigative Site

Madrid, 28009, Spain

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Novartis Investigative Site

Madrid, 28034, Spain

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Novartis Investigative Site

Madrid, 28040, Spain

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Malmo, SE-205 02, Sweden

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Umeå, 901 85, Sweden

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Bellinzona, 6500, Switzerland

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Geneva, CH 1211, Switzerland

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Novartis Investigative Site

Sankt Gallen, 9007, Switzerland

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Taipei, 10002, Taiwan

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Novartis Investigative Site

Taipei, 11217, Taiwan

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Taoyuan District, 33305, Taiwan

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Adana, 01250, Turkey (Türkiye)

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Ankara, 06230, Turkey (Türkiye)

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Istanbul, 34722, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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Sutton, Surrey, SM2 5PT, United Kingdom

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Cambridge, CB2 0QQ, United Kingdom

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Liverpool, CH63 4JY, United Kingdom

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London, EC1A 7BE, United Kingdom

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Novartis Investigative Site

Oxford, OX3 7LE, United Kingdom

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MeSH Terms

Interventions

NIS-793; 130-nm albumin-bound paclitaxel; Gemcitabine

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2021
• First Posted: June 23, 2021
• Study Start: September 30, 2021
• Primary Completion: August 13, 2024
• Study Completion: August 13, 2024
• Last Updated: January 7, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

KR (3); FR (9); TW (3); AU (2); ES (6); US (9); IL (3); NL (1); SL (3); NO (2); BR (4); GR (2); GB (5); IT (4); HU (3); BE (4); FI (2); SG (1); CZ (4); CA (3); RU (2); SE (2); CH (3); JP (6); TU (4); DE (7); CN (16)