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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)

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ClinicalTrials.gov Identifier: NCT04390763
Recruitment Status : Recruiting
First Posted : May 18, 2020
Last Update Posted : December 16, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE May 14, 2020
First Posted Date  ICMJE May 18, 2020
Last Update Posted Date December 16, 2020
Actual Study Start Date  ICMJE October 16, 2020
Estimated Primary Completion Date August 4, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 14, 2020)
  • Incidence of DLTs during the Safety Run-in [ Time Frame: 3 months ]
    Incidence of DLTs to assess the safety and tolerability of NIS793 + spartalizumab in combination with gemcitabine/nab-paclitaxel
  • Incidence and severity of treatment emergent Adverse Events and Serious Adverse Events in Safety Run-in [ Time Frame: 3 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.
  • Dose interruptions/reductions in Safety Run-in [ Time Frame: 3 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
  • Dose intensity in Safety Run-in [ Time Frame: 3 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
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2020)
  • 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.
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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)
  • 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)
  • 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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Efficacy and Safety of NIS793 (With and Without Spartalizumab) in Combination With SOC Chemotherapy in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC)
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Pancreatic Ductal Adenocarcinoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: Safety Run-in
    Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel
    Interventions:
    • Biological: NIS793
    • Biological: Spartalizumab
    • Drug: gemcitabine
    • Drug: nab-paclitaxel
  • Experimental: Randomized Arm 1
    Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel
    Interventions:
    • Biological: NIS793
    • Biological: Spartalizumab
    • Drug: gemcitabine
    • Drug: nab-paclitaxel
  • Experimental: Randomized Arm 2
    Combination of NIS793 + gemcitabine + nab-paclitaxel
    Interventions:
    • Biological: NIS793
    • Drug: gemcitabine
    • Drug: nab-paclitaxel
  • Active Comparator: Randomized Arm 3
    gemcitabine + nab-paclitaxel
    Interventions:
    • Drug: gemcitabine
    • Drug: nab-paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 14, 2020)
156
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 4, 2022
Estimated Primary Completion Date August 4, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Czechia,   Finland,   Italy,   Singapore,   Switzerland,   Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04390763
Other Study ID Numbers  ICMJE CNIS793B12201
2020-000349-14 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP