- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04390763
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)
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)
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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New South Wales
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Westmead, New South Wales, Australia, 2145
- Novartis Investigative Site
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Victoria
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Melbourne, Victoria, Australia, 3000
- Novartis Investigative Site
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Salzburg, Austria, 5020
- Novartis Investigative Site
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Wien, Austria, A-1090
- Novartis Investigative Site
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Liege, Belgium, 4000
- Novartis Investigative Site
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Czech Republic
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Brno, Czech Republic, Czechia, 656 53
- Novartis Investigative Site
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HUS, Finland, FIN-00029
- Novartis Investigative Site
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Paris 10, France, 75475
- Novartis Investigative Site
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Toulouse 4, France, 31054
- Novartis Investigative Site
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Essen, Germany, 45147
- Novartis Investigative Site
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Heidelberg, Germany, 69120
- Novartis Investigative Site
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Ulm, Germany, 89081
- Novartis Investigative Site
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MI
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Milano, MI, Italy, 20132
- Novartis Investigative Site
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Milano, MI, Italy, 20141
- Novartis Investigative Site
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Rozzano, MI, Italy, 20089
- Novartis Investigative Site
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VR
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Verona, VR, Italy, 37126
- Novartis Investigative Site
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Singapore, Singapore, 119074
- Novartis Investigative Site
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Singapore, Singapore, 168583
- Novartis Investigative Site
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Madrid, Spain, 28050
- Novartis Investigative Site
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Catalunya
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Barcelona, Catalunya, Spain, 08035
- Novartis Investigative Site
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Barcelona, Catalunya, Spain, 08036
- Novartis Investigative Site
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St. Gallen, Switzerland, 9007
- Novartis Investigative Site
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Zurich, Switzerland, 8091
- Novartis Investigative Site
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Taichung, Taiwan, 40447
- Novartis Investigative Site
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Taipei, Taiwan, 10002
- Novartis Investigative Site
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Oxford, United Kingdom, OX3 7LJ
- Novartis Investigative Site
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Georgia
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Atlanta, Georgia, United States, 30322
- Winship Cancer Institute Main Centre
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Maryland
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Baltimore, Maryland, United States, 21231
- Sidney Kimmel CCC At JH
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital Massachusetts General Hospital
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Boston, Massachusetts, United States, 02215
- Beth Israel Deaconess Medical Cente
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15232
- University of Pittsburgh Cancer Institute HIllman Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Signed informed consent must be obtained prior to participation in the study.
- Male or female ≥ 18 years of age at the time of informed consent.
- Participants with histologically or cytologically confirmed treatment-naïve metastatic adenocarcinoma of the pancreas with measurable disease as per RECIST 1.1.
- 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.
- ECOG performance status ≤ 1.
Exclusion Criteria:
- 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.
- Participants amenable to potentially curative resection.
- Participants with a diagnosis of pancreatic neuroendocrine tumors (NETs), acinar, or islet cell tumors.
- Having out of range laboratory values as pre-defined in the protocol.
- Participants with MSI-H pancreatic adenocarcinoma.
- 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.
- History of severe hypersensitivity reactions to any ingredient of study drug(s) and other mAbs and/or their excipients.
- 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.
- Impaired cardiac function or clinically significant cardiac disease.
- Known history of testing positive HIV infection.
- Active HBV or HCV infection. Participants whose disease is controlled under antiviral therapy should not be excluded.
- History of or current interstitial lung disease or pneumonitis grade ≥ 2
- 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
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 |
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Experimental: Safety Run-in
Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel
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anti-TGFb antibody
anti-PD-1 antibody
Other Names:
SOC chemotherapy
SOC chemotherapy
Other Names:
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Experimental: Randomized Arm 1
Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel
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anti-TGFb antibody
anti-PD-1 antibody
Other Names:
SOC chemotherapy
SOC chemotherapy
Other Names:
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Experimental: Randomized Arm 2
Combination of NIS793 + gemcitabine + nab-paclitaxel
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anti-TGFb antibody
SOC chemotherapy
SOC chemotherapy
Other Names:
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Active Comparator: Randomized Arm 3
gemcitabine + nab-paclitaxel
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SOC chemotherapy
SOC chemotherapy
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Incidence of DLTs during the Safety Run-in
Time Frame: 8 months
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Incidence of DLTs to assess the safety and tolerability of NIS793 + spartalizumab in combination with gemcitabine/nab-paclitaxel
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8 months
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Incidence and severity of treatment emergent Adverse Events and Serious Adverse Events in Safety Run-in
Time Frame: 8 months
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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:
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8 months
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Dose interruptions/reductions in Safety Run-in
Time Frame: 8 months
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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
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8 months
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Dose intensity in Safety Run-in
Time Frame: 8 months
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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
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8 months
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Progression-free survival in Randomized part
Time Frame: 18 months
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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
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18 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Incidence and severity of Adverse Events and Serious Adverse Events in Randomized part
Time Frame: 18 months
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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:
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18 months
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Overall response rate per RECIST 1.1 in Randomized part
Time Frame: 18 months
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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
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18 months
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Duration of response per RECIST 1.1 in Randomized part
Time Frame: 18 months
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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
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18 months
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Time to Progression per RECIST 1.1 in Randomized part
Time Frame: 18 months
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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
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18 months
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Overall Survival per RECIST 1.1 in Randomized part
Time Frame: 18 months
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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
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18 months
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CD8 and PD-L1 expression in Randomized part
Time Frame: 18 months
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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
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18 months
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Antidrug antibodies (ADA) (anti-NIS793 and anti-spartalizumab) expression in Randomized part
Time Frame: 18 months
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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
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18 months
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Pharmacokinetic (PK) parameter Cmax in Randomized part
Time Frame: 12 months
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To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)
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12 months
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Pharmacokinetic parameter AUClast in Randomized part
Time Frame: 12 months
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To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)
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12 months
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Pharmacokinetic parameter Ctrough
Time Frame: 12 months
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To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)
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12 months
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Adenocarcinoma
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Paclitaxel
- Spartalizumab
- Gemcitabine
Other Study ID Numbers
- CNIS793B12201
- 2020-000349-14 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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