Clinical Trials /

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

NCT04390763

Description:

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.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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: 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)

Clinical Trial IDs

  • ORG STUDY ID: CNIS793B12201
  • SECONDARY ID: 2020-000349-14
  • NCT ID: NCT04390763

Conditions

  • Metastatic Pancreatic Ductal Adenocarcinoma

Interventions

DrugSynonymsArms
NIS793Randomized Arm 1
SpartalizumabPDR001Randomized Arm 1
gemcitabineRandomized Arm 1
nab-paclitaxelabraxaneRandomized Arm 1

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Safety Run-inExperimentalCombination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel
  • NIS793
  • Spartalizumab
  • gemcitabine
  • nab-paclitaxel
Randomized Arm 1ExperimentalCombination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel
  • NIS793
  • Spartalizumab
  • gemcitabine
  • nab-paclitaxel
Randomized Arm 2ExperimentalCombination of NIS793 + gemcitabine + nab-paclitaxel
  • NIS793
  • gemcitabine
  • nab-paclitaxel
Randomized Arm 3Active Comparatorgemcitabine + nab-paclitaxel
  • gemcitabine
  • nab-paclitaxel

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of DLTs during the Safety Run-in
Time Frame:3 months
Safety Issue:
Description:Incidence of DLTs to assess the safety and tolerability of NIS793 + spartalizumab in combination with gemcitabine/nab-paclitaxel

Secondary Outcome Measures

Measure:Incidence and severity of Adverse Events and Serious Adverse Events in Randomized part
Time Frame:18 months
Safety Issue:
Description: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.
Measure:Overall response rate per RECIST 1.1 in Randomized part
Time Frame:18 months
Safety Issue:
Description: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
Measure:Duration of response per RECIST 1.1 in Randomized part
Time Frame:18 months
Safety Issue:
Description: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
Measure:Time to Progression per RECIST 1.1 in Randomized part
Time Frame:18 months
Safety Issue:
Description: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
Measure:Overall Survival per RECIST 1.1 in Randomized part
Time Frame:18 months
Safety Issue:
Description: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
Measure:CD8 and PD-L1 expression in Randomized part
Time Frame:18 months
Safety Issue:
Description: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
Measure:Antidrug antibodies (ADA) (anti-NIS793 and anti-spartalizumab) expression in Randomized part
Time Frame:18 months
Safety Issue:
Description: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
Measure:Pharmacokinetic (PK) parameter Cmax in Randomized part
Time Frame:12 months
Safety Issue:
Description:To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)
Measure:Pharmacokinetic parameter AUClast in Randomized part
Time Frame:12 months
Safety Issue:
Description:To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)
Measure:Pharmacokinetic parameter Ctrough
Time Frame:12 months
Safety Issue:
Description:To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • NIS793, spartalizumab, gemcitabine, nab-paclitaxel, mPDAC, TGFβ, PD-1, Phase II

Last Updated

May 14, 2020