Study of Efficacy and Safety of NIS793 (With and Without Spartalizumab) in Combination With SOC Chemotherapy in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) (daNIS-1)

January 24, 2024 updated by: Novartis Pharmaceuticals

A Phase II, Open Label, Randomized, Parallel Arm Study of NIS793 (With and Without Spartalizumab) in Combination With SOC Chemotherapy Gemcitabine/Nab-paclitaxel, and Gemcitabine/Nab-paclitaxel Alone in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC)

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 untreated mPDAC.

Study Overview

Study Type

Interventional

Enrollment (Actual)

151

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • New South Wales
      • Westmead, New South Wales, Australia, 2145
        • Novartis Investigative Site
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Novartis Investigative Site
      • Salzburg, Austria, 5020
        • Novartis Investigative Site
      • Wien, Austria, A-1090
        • Novartis Investigative Site
      • Liege, Belgium, 4000
        • Novartis Investigative Site
    • Czech Republic
      • Brno, Czech Republic, Czechia, 656 53
        • Novartis Investigative Site
      • HUS, Finland, FIN-00029
        • Novartis Investigative Site
      • Paris 10, France, 75475
        • Novartis Investigative Site
      • Toulouse 4, France, 31054
        • Novartis Investigative Site
      • Essen, Germany, 45147
        • Novartis Investigative Site
      • Heidelberg, Germany, 69120
        • Novartis Investigative Site
      • Ulm, Germany, 89081
        • Novartis Investigative Site
    • MI
      • Milano, MI, Italy, 20132
        • Novartis Investigative Site
      • Milano, MI, Italy, 20141
        • Novartis Investigative Site
      • Rozzano, MI, Italy, 20089
        • Novartis Investigative Site
    • VR
      • Verona, VR, Italy, 37126
        • Novartis Investigative Site
      • Singapore, Singapore, 119074
        • Novartis Investigative Site
      • Singapore, Singapore, 168583
        • Novartis Investigative Site
      • Madrid, Spain, 28050
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Novartis Investigative Site
      • Barcelona, Catalunya, Spain, 08036
        • Novartis Investigative Site
      • St. Gallen, Switzerland, 9007
        • Novartis Investigative Site
      • Zurich, Switzerland, 8091
        • Novartis Investigative Site
      • Taichung, Taiwan, 40447
        • Novartis Investigative Site
      • Taipei, Taiwan, 10002
        • Novartis Investigative Site
      • Oxford, United Kingdom, OX3 7LJ
        • Novartis Investigative Site
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute Main Centre
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • Sidney Kimmel CCC At JH
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Cente
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Cancer Institute HIllman Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Safety Run-in
Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel
anti-TGFb antibody
anti-PD-1 antibody
Other Names:
  • PDR001
SOC chemotherapy
SOC chemotherapy
Other Names:
  • abraxane
Experimental: Randomized Arm 1
Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel
anti-TGFb antibody
anti-PD-1 antibody
Other Names:
  • PDR001
SOC chemotherapy
SOC chemotherapy
Other Names:
  • abraxane
Experimental: Randomized Arm 2
Combination of NIS793 + gemcitabine + nab-paclitaxel
anti-TGFb antibody
SOC chemotherapy
SOC chemotherapy
Other Names:
  • abraxane
Active Comparator: Randomized Arm 3
gemcitabine + nab-paclitaxel
SOC chemotherapy
SOC chemotherapy
Other Names:
  • abraxane

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of DLTs during the Safety Run-in
Time Frame: 8 months
Incidence of DLTs to assess the safety and tolerability of NIS793 + spartalizumab in combination with gemcitabine/nab-paclitaxel
8 months
Incidence and severity of treatment emergent Adverse Events and Serious Adverse Events in Safety Run-in
Time Frame: 8 months

Safety and tolerability measured by appearance of (or worsening of any pre-existing condition) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient signed informed consent.

A Serious Adverse Event (SAE) is defined as one of the following:

  • Is fatal or life threatening
  • Results in persistent or significant disability/incapacity
  • Constitutes a congenital anomaly/birth defect
  • Is medical significant
  • Requires inpatient hospitalization or prolongation of existing hospitalization.
8 months
Dose interruptions/reductions in Safety Run-in
Time Frame: 8 months
Tolerability of NIS793 + spartalizumab in combination with gemcitabine/nab-paclitaxel measured by the number of subjects with at least one dose interruption/reduction of study treatment and reason
8 months
Dose intensity in Safety Run-in
Time Frame: 8 months
Tolerability of NIS793 + spartalizumab in combination with gemcitabine/nab-paclitaxel measured by the dose intensity of study treatment for subjects with non-zero duration of exposure computed as the ratio of dose intensity and planned dose intensity
8 months
Progression-free survival in Randomized part
Time Frame: 18 months
PFS as per Response Evaluation Criteria in Solid Tumors (RECIST1.1) as per local Investigator's review, to evaluate the PFS of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel
18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and severity of Adverse Events and Serious Adverse Events in Randomized part
Time Frame: 18 months

Safety and tolerability measured by appearance of (or worsening of any pre-existing condition) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient signed informed consent.

A Serious Adverse Event (SAE) is defined as one of the following:

  • Is fatal or life threatening
  • Results in persistent or significant disability/incapacity
  • Constitutes a congenital anomaly/birth defect
  • Is medical significant
  • Requires inpatient hospitalization or prolongation of existing hospitalization.
18 months
Overall response rate per RECIST 1.1 in Randomized part
Time Frame: 18 months
ORR per RECIST 1.1 to assess the preliminary anti-tumor activity of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel
18 months
Duration of response per RECIST 1.1 in Randomized part
Time Frame: 18 months
DOR per RECIST 1.1 to assess the preliminary anti-tumor activity of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel
18 months
Time to Progression per RECIST 1.1 in Randomized part
Time Frame: 18 months
TTP per RECIST 1.1 to assess the preliminary anti-tumor activity of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel
18 months
Overall Survival per RECIST 1.1 in Randomized part
Time Frame: 18 months
OS per RECIST 1.1 to assess the preliminary anti-tumor activity of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel
18 months
CD8 and PD-L1 expression in Randomized part
Time Frame: 18 months
Change from baseline in CD8 and PD-L1 IHC related markers to assess the CD8 and PD-L1 status of the participants at screening and on treatment versus gemcitabine/nab-paclitaxel
18 months
Antidrug antibodies (ADA) (anti-NIS793 and anti-spartalizumab) expression in Randomized part
Time Frame: 18 months
Antidrug antibodies (ADA) prevalence at baseline and ADA incidence on-treatment (anti-NIS793 and anti-spartalizumab) to characterize the incidence of immunogenicity of NIS793 and spartalizumab in combination with gemcitabine/nab-paclitaxel
18 months
Pharmacokinetic (PK) parameter Cmax in Randomized part
Time Frame: 12 months
To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)
12 months
Pharmacokinetic parameter AUClast in Randomized part
Time Frame: 12 months
To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)
12 months
Pharmacokinetic parameter Ctrough
Time Frame: 12 months
To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 16, 2020

Primary Completion (Estimated)

April 16, 2024

Study Completion (Estimated)

April 16, 2024

Study Registration Dates

First Submitted

May 14, 2020

First Submitted That Met QC Criteria

May 14, 2020

First Posted (Actual)

May 18, 2020

Study Record Updates

Last Update Posted (Estimated)

January 25, 2024

Last Update Submitted That Met QC Criteria

January 24, 2024

Last Verified

January 1, 2024

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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