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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)

Primary Purpose

Metastatic Pancreatic Ductal Adenocarcinoma

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
NIS793
Spartalizumab
gemcitabine
nab-paclitaxel
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Pancreatic Ductal Adenocarcinoma focused on measuring NIS793, spartalizumab, gemcitabine, nab-paclitaxel, mPDAC, TGFβ, PD-1, Phase II

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Winship Cancer Institute Main Centre
  • Sidney Kimmel CCC At JH
  • Massachusetts General Hospital Massachusetts General Hospital
  • Beth Israel Deaconess Medical Cente
  • University of Pittsburgh Cancer Institute HIllman Cancer Center
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Arm Label

Safety Run-in

Randomized Arm 1

Randomized Arm 2

Randomized Arm 3

Arm Description

Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel

Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel

Combination of NIS793 + gemcitabine + nab-paclitaxel

gemcitabine + nab-paclitaxel

Outcomes

Primary Outcome Measures

Incidence of DLTs during the Safety Run-in
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
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
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
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
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

Incidence and severity of Adverse Events and Serious Adverse Events in Randomized part
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
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
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
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
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
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
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
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
To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)
Pharmacokinetic parameter Ctrough
To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)

Full Information

First Posted
May 14, 2020
Last Updated
October 9, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT04390763
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)
Acronym
daNIS-1
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 16, 2020 (Actual)
Primary Completion Date
April 16, 2024 (Anticipated)
Study Completion Date
April 16, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Pancreatic Ductal Adenocarcinoma
Keywords
NIS793, spartalizumab, gemcitabine, nab-paclitaxel, mPDAC, TGFβ, PD-1, Phase II

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
151 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Safety Run-in
Arm Type
Experimental
Arm Description
Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel
Arm Title
Randomized Arm 1
Arm Type
Experimental
Arm Description
Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel
Arm Title
Randomized Arm 2
Arm Type
Experimental
Arm Description
Combination of NIS793 + gemcitabine + nab-paclitaxel
Arm Title
Randomized Arm 3
Arm Type
Active Comparator
Arm Description
gemcitabine + nab-paclitaxel
Intervention Type
Biological
Intervention Name(s)
NIS793
Intervention Description
anti-TGFb antibody
Intervention Type
Biological
Intervention Name(s)
Spartalizumab
Other Intervention Name(s)
PDR001
Intervention Description
anti-PD-1 antibody
Intervention Type
Drug
Intervention Name(s)
gemcitabine
Intervention Description
SOC chemotherapy
Intervention Type
Drug
Intervention Name(s)
nab-paclitaxel
Other Intervention Name(s)
abraxane
Intervention Description
SOC chemotherapy
Primary Outcome Measure Information:
Title
Incidence of DLTs during the Safety Run-in
Description
Incidence of DLTs to assess the safety and tolerability of NIS793 + spartalizumab in combination with gemcitabine/nab-paclitaxel
Time Frame
8 months
Title
Incidence and severity of treatment emergent Adverse Events and Serious Adverse Events in Safety Run-in
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.
Time Frame
8 months
Title
Dose interruptions/reductions in Safety Run-in
Description
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
Time Frame
8 months
Title
Dose intensity in Safety Run-in
Description
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
Time Frame
8 months
Title
Progression-free survival in Randomized part
Description
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
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Incidence and severity of Adverse Events and Serious Adverse Events in Randomized part
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.
Time Frame
18 months
Title
Overall response rate per RECIST 1.1 in Randomized part
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
Time Frame
18 months
Title
Duration of response per RECIST 1.1 in Randomized part
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
Time Frame
18 months
Title
Time to Progression per RECIST 1.1 in Randomized part
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
Time Frame
18 months
Title
Overall Survival per RECIST 1.1 in Randomized part
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
Time Frame
18 months
Title
CD8 and PD-L1 expression in Randomized part
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
Time Frame
18 months
Title
Antidrug antibodies (ADA) (anti-NIS793 and anti-spartalizumab) expression in Randomized part
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
Time Frame
18 months
Title
Pharmacokinetic (PK) parameter Cmax in Randomized part
Description
To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)
Time Frame
12 months
Title
Pharmacokinetic parameter AUClast in Randomized part
Description
To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)
Time Frame
12 months
Title
Pharmacokinetic parameter Ctrough
Description
To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Winship Cancer Institute Main Centre
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Sidney Kimmel CCC At JH
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Massachusetts General Hospital Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Beth Israel Deaconess Medical Cente
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Pittsburgh Cancer Institute HIllman Cancer Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Novartis Investigative Site
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Novartis Investigative Site
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Facility Name
Novartis Investigative Site
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
Facility Name
Novartis Investigative Site
City
Wien
ZIP/Postal Code
A-1090
Country
Austria
Facility Name
Novartis Investigative Site
City
Liege
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Brno
State/Province
Czech Republic
ZIP/Postal Code
656 53
Country
Czechia
Facility Name
Novartis Investigative Site
City
HUS
ZIP/Postal Code
FIN-00029
Country
Finland
Facility Name
Novartis Investigative Site
City
Paris 10
ZIP/Postal Code
75475
Country
France
Facility Name
Novartis Investigative Site
City
Toulouse 4
ZIP/Postal Code
31054
Country
France
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Novartis Investigative Site
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20132
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20141
Country
Italy
Facility Name
Novartis Investigative Site
City
Rozzano
State/Province
MI
ZIP/Postal Code
20089
Country
Italy
Facility Name
Novartis Investigative Site
City
Verona
State/Province
VR
ZIP/Postal Code
37126
Country
Italy
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
119074
Country
Singapore
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
168583
Country
Singapore
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08036
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Novartis Investigative Site
City
St. Gallen
ZIP/Postal Code
9007
Country
Switzerland
Facility Name
Novartis Investigative Site
City
Zurich
ZIP/Postal Code
8091
Country
Switzerland
Facility Name
Novartis Investigative Site
City
Taichung
ZIP/Postal Code
40447
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Oxford
ZIP/Postal Code
OX3 7LJ
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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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