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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04390763




Registration number
NCT04390763
Ethics application status
Date submitted
14/05/2020
Date registered
18/05/2020
Date last updated
28/05/2025

Titles & IDs
Public 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)
Scientific 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)
Secondary ID [1] 0 0
2020-000349-14
Secondary ID [2] 0 0
CNIS793B12201
Universal Trial Number (UTN)
Trial acronym
daNIS-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Pancreatic Ductal Adenocarcinoma 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - NIS793
Treatment: Other - Spartalizumab
Treatment: Drugs - gemcitabine
Treatment: Drugs - nab-paclitaxel

Experimental: Safety Run-in - Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel

Experimental: Randomized Arm 1 - Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel

Experimental: Randomized Arm 2 - Combination of NIS793 + gemcitabine + nab-paclitaxel

Active comparator: Randomized Arm 3 - gemcitabine + nab-paclitaxel


Treatment: Other: NIS793
anti-TGFb antibody. NIS793 2100 mg every 2 weeks by intravenous (i.v.) infusion.

Treatment: Other: Spartalizumab
anti-PD-1 antibody. spartalizumab 400 mg every 4 weeks by i.v. infusion.

Treatment: Drugs: gemcitabine
SOC chemotherapy. Gemcitabine (1000 mg/m\^2 on Days 1, 8, and 15) i.v. given as per label.

Treatment: Drugs: nab-paclitaxel
SOC chemotherapy. Nab-paclitaxel (125 mg/m\^2 on Days 1, 8, and 15) i.v. given as per label.

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety run-in Part: Number of Participants With Dose-Limiting Toxicities (DLTs)
Timepoint [1] 0 0
First cycle of treatment (28 days)
Primary outcome [2] 0 0
Safety run-in Part: Number of Participants With AEs and SAEs During the On-treatment Period
Timepoint [2] 0 0
Up to approximately 0.8 years
Primary outcome [3] 0 0
Safety run-in Part: Number of Participants With Dose Reductions and Dose Interruptions of NIS793, Spartalizumab, Gemcitabine and Nab-paclitaxel
Timepoint [3] 0 0
Up to approximately 0.7 years
Primary outcome [4] 0 0
Safety run-in Part: Dose Intensity of NIS793 and Spartalizumab
Timepoint [4] 0 0
Cycle 1 and Cycle 3. The duration of each cycle was 28 days.
Primary outcome [5] 0 0
Safety run-in Part: Dose Intensity of Gemcitabine and Nab-paclitaxel
Timepoint [5] 0 0
Cycle 1 and Cycle 3. The duration of each cycle was 28 days.
Primary outcome [6] 0 0
Randomized Part: Progression-Free Survival (PFS) Per RECIST v1.1 - Bayesian Model
Timepoint [6] 0 0
Up to approximately 2 years. Risk changing timepoint=approximately 0.3 years.
Primary outcome [7] 0 0
Randomized Part: Progression-Free Survival (PFS) Per RECIST v1.1 - Kaplan-Meier Curves and Cox Model
Timepoint [7] 0 0
Up to approximately 2 years
Secondary outcome [1] 0 0
Randomized Part: Number of Participants With AEs and SAEs During the On-treatment Period
Timepoint [1] 0 0
Up to approximately 1.8 years
Secondary outcome [2] 0 0
Randomized Part: Number of Participants With Dose Reductions and Dose Interruptions of NIS793, Spartalizumab, Gemcitabine and Nab-paclitaxel
Timepoint [2] 0 0
Up to approximately 1.7 years
Secondary outcome [3] 0 0
Randomized Part: Dose Intensity of NIS973 and Spartalizumab
Timepoint [3] 0 0
Cycle 1 and Cycle 3. The duration of each cycle was 28 days
Secondary outcome [4] 0 0
Randomized Part: Dose Intensity of Gemcitabine and Nab-paclitaxel
Timepoint [4] 0 0
Cycle 1 and Cycle 3. The duration of each cycle was 28 days
Secondary outcome [5] 0 0
Randomized Part: Overall Response Rate (ORR) Per RECIST v1.1
Timepoint [5] 0 0
Up to approximately 1.7 years
Secondary outcome [6] 0 0
Randomized Part: Duration of Response (DOR) Per RECIST v1.1
Timepoint [6] 0 0
Up to approximately 1.7 years
Secondary outcome [7] 0 0
Randomized Part: Time to Progression (TTP) Per RECIST v1.1
Timepoint [7] 0 0
Up to approximately 1.7 years
Secondary outcome [8] 0 0
Randomized Part: Overall Survival (OS)
Timepoint [8] 0 0
Up to approximately 2 years
Secondary outcome [9] 0 0
Randomized Part: Change From Baseline in PD-L1 Expression
Timepoint [9] 0 0
Baseline (Screening), on-treatment (anytime between Cycle 3 Day 2 and Day 4). The duration of each cycle was 28 days.
Secondary outcome [10] 0 0
Randomized Part: Change From Baseline in CD8 Expression
Timepoint [10] 0 0
Baseline (Screening), on-treatment (anytime between Cycle 3 Day 2 and Day 4). The duration of each cycle was 28 days.
Secondary outcome [11] 0 0
Randomized Part: Number of Participants With Anti-NIS793 Antibodies
Timepoint [11] 0 0
Baseline (before first dose) and post-baseline (assessed throughout the treatment up to approximately 1.7 years)
Secondary outcome [12] 0 0
Randomized Part: Number of Participants With Anti-spartalizumab Antibodies
Timepoint [12] 0 0
Cycle 1 and Cycle 3. The duration of each cycle was 28 days
Secondary outcome [13] 0 0
Randomized Part: Maximum Observed Serum Concentration (Cmax) of NIS793
Timepoint [13] 0 0
Cycle 1 and Cycle 3: pre-dose, 1, 24, 168 and 336 hours after the end of the infusion on Day 1. The duration of the infusion was 30 minutes. One cycle=28 days
Secondary outcome [14] 0 0
Randomized Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of NIS793
Timepoint [14] 0 0
Cycle 1 and Cycle 3: pre-dose, 1, 24, 168 and 336 hours after the end of the infusion on Day 1. The duration of the infusion was 30 minutes. One cycle=28 days
Secondary outcome [15] 0 0
Randomized Part: Trough Serum Concentration (Ctrough) of NIS793
Timepoint [15] 0 0
Cycle 1: pre-dose on Day 1. Cycle 3: pre-dose on Day 1 and Day 15 (combined). One cycle=28 days
Secondary outcome [16] 0 0
Randomized Part: Maximum Observed Serum Concentration (Cmax) of Spartalizumab
Timepoint [16] 0 0
Cycle 1 and Cycle 3: pre-dose, 1, 24, 168 and 648 hours after the end of the infusion on Day 1. The duration of the infusion was 30 minutes. One cycle=28 days
Secondary outcome [17] 0 0
Randomized Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Spartalizumab
Timepoint [17] 0 0
Cycle 1 and Cycle 3: pre-dose, 1, 24, 168 and 648 hours after the end of the infusion on Day 1. The duration of the infusion was 30 minutes. One cycle=28 days
Secondary outcome [18] 0 0
Randomized Part: Trough Serum Concentration (Ctrough) of Spartalizumab
Timepoint [18] 0 0
Cycle 2, 3 and 4: pre-dose on Day 1. One cycle=28 days
Secondary outcome [19] 0 0
Randomized Part: Maximum Observed Plasma Concentration (Cmax) of Gemcitabine
Timepoint [19] 0 0
Cycle 1 and Cycle 4: pre-dose, end of infusion, and 2, 3, 5 and 24 hours after the start of infusion on Day 1. The duration of the infusion was according to the product labelling and local guidance. One cycle=28 days
Secondary outcome [20] 0 0
Randomized Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Gemcitabine
Timepoint [20] 0 0
Cycle 1 and Cycle 4: pre-dose, end of infusion, and 2, 3, 5 and 24 hours after the start of infusion on Day 1. The duration of the infusion was according to the product labelling and local guidance. One cycle=28 days
Secondary outcome [21] 0 0
Randomized Part: Trough Serum Concentration (Ctrough) of Gemcitabine
Timepoint [21] 0 0
Cycle 4: pre-dose on Day 1. One cycle=28 days
Secondary outcome [22] 0 0
Randomized Part: Maximum Observed Plasma Concentration (Cmax) of Nab-paclitaxel
Timepoint [22] 0 0
Cycle 1 and Cycle 4: pre-dose, end of infusion, and 2, 3, 5 and 24 hours after the start of infusion on Day 1. The duration of the infusion was according to the product labelling and local guidance. One cycle=28 days
Secondary outcome [23] 0 0
Randomized Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Nab-paclitaxel
Timepoint [23] 0 0
Cycle 1 and Cycle 4: pre-dose, end of infusion, and 2, 3, 5 and 24 hours after the start of infusion on Day 1. The duration of the infusion was according to the product labelling and local guidance. One cycle=28 days
Secondary outcome [24] 0 0
Randomized Part: Trough Serum Concentration (Ctrough) of Nab-paclitaxel
Timepoint [24] 0 0
Cycle 4: pre-dose on Day 1. One cycle=28 days

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Westmead
Recruitment hospital [2] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Georgia
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
Austria
State/province [5] 0 0
Salzburg
Country [6] 0 0
Austria
State/province [6] 0 0
Wien
Country [7] 0 0
Belgium
State/province [7] 0 0
Liege
Country [8] 0 0
Czechia
State/province [8] 0 0
Czech Republic
Country [9] 0 0
Finland
State/province [9] 0 0
Helsinki
Country [10] 0 0
France
State/province [10] 0 0
Paris 10
Country [11] 0 0
France
State/province [11] 0 0
Toulouse 4
Country [12] 0 0
Germany
State/province [12] 0 0
Essen
Country [13] 0 0
Germany
State/province [13] 0 0
Heidelberg
Country [14] 0 0
Germany
State/province [14] 0 0
Ulm
Country [15] 0 0
Italy
State/province [15] 0 0
MI
Country [16] 0 0
Italy
State/province [16] 0 0
VR
Country [17] 0 0
Singapore
State/province [17] 0 0
Singapore
Country [18] 0 0
Spain
State/province [18] 0 0
Catalunya
Country [19] 0 0
Spain
State/province [19] 0 0
Madrid
Country [20] 0 0
Switzerland
State/province [20] 0 0
St Gallen
Country [21] 0 0
Switzerland
State/province [21] 0 0
Zuerich
Country [22] 0 0
Taiwan
State/province [22] 0 0
Taichung
Country [23] 0 0
Taiwan
State/province [23] 0 0
Taipei
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.