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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04390763
Recruitment Status : Active, not recruiting
First Posted : May 18, 2020
Last Update Posted : May 31, 2023
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Ductal Adenocarcinoma Biological: NIS793 Biological: Spartalizumab Drug: gemcitabine Drug: nab-paclitaxel Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 151 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : October 16, 2020
Estimated Primary Completion Date : November 30, 2023
Estimated Study Completion Date : November 30, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Safety Run-in
Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel
 Biological: NIS793
anti-TGFb antibody

Biological: Spartalizumab
anti-PD-1 antibody
Other Name: PDR001

Drug: gemcitabine
SOC chemotherapy

Drug: nab-paclitaxel
SOC chemotherapy
Other Name: abraxane
Experimental: Randomized Arm 1
Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel
 Biological: NIS793
anti-TGFb antibody

Biological: Spartalizumab
anti-PD-1 antibody
Other Name: PDR001

Drug: gemcitabine
SOC chemotherapy

Drug: nab-paclitaxel
SOC chemotherapy
Other Name: abraxane
Experimental: Randomized Arm 2
Combination of NIS793 + gemcitabine + nab-paclitaxel
 Biological: NIS793
anti-TGFb antibody

Drug: gemcitabine
SOC chemotherapy

Drug: nab-paclitaxel
SOC chemotherapy
Other Name: abraxane
Active Comparator: Randomized Arm 3
gemcitabine + nab-paclitaxel
 Drug: gemcitabine
SOC chemotherapy

Drug: nab-paclitaxel
SOC chemotherapy
Other Name: abraxane


Outcome Measures
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Primary Outcome Measures :
  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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


Secondary Outcome Measures :
  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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)

  9. 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)

  10. 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)


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04390763


Locations
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United States, Georgia
Emory University School of Medicine/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Maryland
Sidney Kimmel CCC at JH
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Massachusetts General Hospital Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Cente
Boston, Massachusetts, United States, 02215
United States, Pennsylvania
University of Pittsburgh Cancer Institute HIllman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
Australia, New South Wales
Novartis Investigative Site
Westmead, New South Wales, Australia, 2145
Australia, Victoria
Novartis Investigative Site
Melbourne, Victoria, Australia, 3000
Austria
Novartis Investigative Site
Salzburg, Austria, 5020
Novartis Investigative Site
Wien, Austria, A-1090
Belgium
Novartis Investigative Site
Liege, Belgium, 4000
Czechia
Novartis Investigative Site
Brno, Czech Republic, Czechia, 656 53
Finland
Novartis Investigative Site
HUS, Finland, FIN-00029
France
Novartis Investigative Site
Paris Cedex 10, France, 75475
Novartis Investigative Site
Toulouse Cedex 4, France, 31054
Germany
Novartis Investigative Site
Essen, Germany, 45147
Novartis Investigative Site
Heidelberg, Germany, 69120
Novartis Investigative Site
Ulm, Germany, 89081
Italy
Novartis Investigative Site
Milano, MI, Italy, 20132
Novartis Investigative Site
Milano, MI, Italy, 20141
Novartis Investigative Site
Rozzano, MI, Italy, 20089
Novartis Investigative Site
Verona, VR, Italy, 37126
Singapore
Novartis Investigative Site
Singapore, Singapore, 119074
Novartis Investigative Site
Singapore, Singapore, 168583
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site
Madrid, Spain, 28050
Switzerland
Novartis Investigative Site
St. Gallen, Switzerland, 9007
Novartis Investigative Site
Zurich, Switzerland, 8091
Taiwan
Novartis Investigative Site
Taichung, Taiwan, 40447
Novartis Investigative Site
Taipei, Taiwan, 10002
United Kingdom
Novartis Investigative Site
Oxford, United Kingdom, OX3 7LJ
Sponsors and Collaborators
Novartis Pharmaceuticals
More Information
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04390763    
Other Study ID Numbers: CNIS793B12201
2020-000349-14 ( EudraCT Number )
First Posted: May 18, 2020    Key Record Dates
Last Update Posted: May 31, 2023
Last Verified: May 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
NIS793, spartalizumab, gemcitabine, nab-paclitaxel, mPDAC, TGFβ, PD-1, Phase II
Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Paclitaxel
Gemcitabine
Spartalizumab
Antineoplastic Agents, Phytogenic
 Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Immune Checkpoint Inhibitors
Antineoplastic Agents, Immunological