Study of Efficacy and Safety of NIS793 (With and Without Spartalizumab) in Combination With SOC Chemotherapy in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC)

NCT ID: NCT04390763

Last Updated: 2025-10-16

Study Results

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Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

164 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-16

Study Completion Date

2024-05-02

Brief Summary

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The purpose of this Phase II study is to assess the efficacy and safety of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in previously untreated mPDAC.

Detailed Description

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This is a randomized, parallel arms, open-label, multi-center, Phase II study to evaluate the efficacy and safety of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel in participants with first-line metastatic pancreatic ductal adenocarcinoma (mPDAC).

The study started with a Safety Run-in to assess the safety and tolerability of NIS793 in combination with spartalizumab and standard of care (SOC) gemcitabine/nab-paclitaxel. Doses defined for each study treatment, as part of this quadruplet were administered in the Randomized part in the quadruplet/triplet/doublet-based treatment arms.

The Randomized part opened after the Safety Run-in had completed. Participants were randomized in a 1:1:1 ratio to one of the three treatment arms:

* Arm 1: NIS793 with spartalizumab and gemcitabine/nab-paclitaxel
* Arm 2: NIS793 with gemcitabine/nab-paclitaxel
* Arm 3: gemcitabine/nab-paclitaxel

Conditions

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Metastatic Pancreatic Ductal Adenocarcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Safety Run-in

Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel

Group Type EXPERIMENTAL

NIS793

Intervention Type BIOLOGICAL

anti-TGFb antibody. NIS793 2100 mg every 2 weeks by intravenous (i.v.) infusion.

Spartalizumab

Intervention Type BIOLOGICAL

anti-PD-1 antibody. spartalizumab 400 mg every 4 weeks by i.v. infusion.

gemcitabine

Intervention Type DRUG

SOC chemotherapy. Gemcitabine (1000 mg/m\^2 on Days 1, 8, and 15) i.v. given as per label.

nab-paclitaxel

Intervention Type DRUG

SOC chemotherapy. Nab-paclitaxel (125 mg/m\^2 on Days 1, 8, and 15) i.v. given as per label.

Randomized Arm 1

Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel

Group Type EXPERIMENTAL

NIS793

Intervention Type BIOLOGICAL

anti-TGFb antibody. NIS793 2100 mg every 2 weeks by intravenous (i.v.) infusion.

Spartalizumab

Intervention Type BIOLOGICAL

anti-PD-1 antibody. spartalizumab 400 mg every 4 weeks by i.v. infusion.

gemcitabine

Intervention Type DRUG

SOC chemotherapy. Gemcitabine (1000 mg/m\^2 on Days 1, 8, and 15) i.v. given as per label.

nab-paclitaxel

Intervention Type DRUG

SOC chemotherapy. Nab-paclitaxel (125 mg/m\^2 on Days 1, 8, and 15) i.v. given as per label.

Randomized Arm 2

Combination of NIS793 + gemcitabine + nab-paclitaxel

Group Type EXPERIMENTAL

NIS793

Intervention Type BIOLOGICAL

anti-TGFb antibody. NIS793 2100 mg every 2 weeks by intravenous (i.v.) infusion.

gemcitabine

Intervention Type DRUG

SOC chemotherapy. Gemcitabine (1000 mg/m\^2 on Days 1, 8, and 15) i.v. given as per label.

nab-paclitaxel

Intervention Type DRUG

SOC chemotherapy. Nab-paclitaxel (125 mg/m\^2 on Days 1, 8, and 15) i.v. given as per label.

Randomized Arm 3

gemcitabine + nab-paclitaxel

Group Type ACTIVE_COMPARATOR

gemcitabine

Intervention Type DRUG

SOC chemotherapy. Gemcitabine (1000 mg/m\^2 on Days 1, 8, and 15) i.v. given as per label.

nab-paclitaxel

Intervention Type DRUG

SOC chemotherapy. Nab-paclitaxel (125 mg/m\^2 on Days 1, 8, and 15) i.v. given as per label.

Interventions

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NIS793

anti-TGFb antibody. NIS793 2100 mg every 2 weeks by intravenous (i.v.) infusion.

Intervention Type BIOLOGICAL

Spartalizumab

anti-PD-1 antibody. spartalizumab 400 mg every 4 weeks by i.v. infusion.

Intervention Type BIOLOGICAL

gemcitabine

SOC chemotherapy. Gemcitabine (1000 mg/m\^2 on Days 1, 8, and 15) i.v. given as per label.

Intervention Type DRUG

nab-paclitaxel

SOC chemotherapy. Nab-paclitaxel (125 mg/m\^2 on Days 1, 8, and 15) i.v. given as per label.

Intervention Type DRUG

Other Intervention Names

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PDR001 abraxane

Eligibility Criteria

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Inclusion Criteria

1. Signed informed consent must be obtained prior to participation in the study.
2. Male or female ≥ 18 years of age at the time of informed consent.
3. Participants with histologically or cytologically confirmed treatment-naïve metastatic adenocarcinoma of the pancreas with measurable disease as per RECIST 1.1.
4. Participants must have a site of disease amenable to biopsy, and be candidate for tumor biopsy according to the treating institution's guidelines. Participants must be willing to undergo a tumor biopsy at screening and during therapy on the study. In the event a new biopsy cannot be safely performed at study entry, an archival sample (collected \<6 months prior) may be substituted following documented discussion with Novartis.
5. ECOG performance status ≤ 1.

Exclusion Criteria

1. Previous radiotherapy, surgery (with exception of placement of biliary stent, which is allowed), chemotherapy or any other investigational therapy for the treatment of metastatic pancreatic cancer. Participants having received previous chemotherapy in the adjuvant setting.
2. Participants amenable to potentially curative resection.
3. Participants with a diagnosis of pancreatic neuroendocrine tumors (NETs), acinar, or islet cell tumors.
4. Having out of range laboratory values as pre-defined in the protocol.
5. Participants with MSI-H pancreatic adenocarcinoma.
6. Presence of symptomatic CNS metastases, or CNS metastases that require local CNS directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids 2 weeks prior to study entry.
7. History of severe hypersensitivity reactions to any ingredient of study drug(s) and other mAbs and/or their excipients.
8. The participant exhibits any of the events outlined in the contra-indications or special warnings and precautions sections of gemcitabine and nab-paclitaxel as per locally approved labels.
9. Impaired cardiac function or clinically significant cardiac disease.
10. Known history of testing positive HIV infection.
11. Active HBV or HCV infection. Participants whose disease is controlled under antiviral therapy should not be excluded.
12. History of or current interstitial lung disease or pneumonitis grade ≥ 2
13. High risk of clinically significant gastrointestinal tract bleeding or any other condition associated with or history of significant bleeding.
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Sidney Kimmel CCC At JH

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Cente

Boston, Massachusetts, United States

Site Status

Univ of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Site Status

Novartis Investigative Site

Westmead, New South Wales, Australia

Site Status

Novartis Investigative Site

Melbourne, Victoria, Australia

Site Status

Novartis Investigative Site

Salzburg, , Austria

Site Status

Novartis Investigative Site

Vienna, , Austria

Site Status

Novartis Investigative Site

Liège, , Belgium

Site Status

Novartis Investigative Site

Brno, Czech Republic, Czechia

Site Status

Novartis Investigative Site

Helsinki, , Finland

Site Status

Novartis Investigative Site

Paris, , France

Site Status

Novartis Investigative Site

Toulouse, , France

Site Status

Novartis Investigative Site

Essen, , Germany

Site Status

Novartis Investigative Site

Heidelberg, , Germany

Site Status

Novartis Investigative Site

Ulm, , Germany

Site Status

Novartis Investigative Site

Milan, MI, Italy

Site Status

Novartis Investigative Site

Milan, MI, Italy

Site Status

Novartis Investigative Site

Rozzano, MI, Italy

Site Status

Novartis Investigative Site

Verona, VR, Italy

Site Status

Novartis Investigative Site

Singapore, , Singapore

Site Status

Novartis Investigative Site

Singapore, , Singapore

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Novartis Investigative Site

Sankt Gallen, , Switzerland

Site Status

Novartis Investigative Site

Zurich, , Switzerland

Site Status

Novartis Investigative Site

Taichung, , Taiwan

Site Status

Novartis Investigative Site

Taipei, , Taiwan

Site Status

Novartis Investigative Site

Oxford, , United Kingdom

Site Status

Countries

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United States Australia Austria Belgium Czechia Finland France Germany Italy Singapore Spain Switzerland Taiwan United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=2577

A Plain Language Trial Summary is available on www.novctrd.com

Other Identifiers

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2020-000349-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CNIS793B12201

Identifier Type: -

Identifier Source: org_study_id

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