Metastatic Pancreatic Ductal AdenocarcinomaPhase 2daNIS-1NCT04390763
Study of Efficacy and Safety of NIS793 (With and Without Spartalizumab) in Combination With SOC Chemotherapy in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC)
A Phase 2 study testing NIS793, Spartalizumab and gemcitabine in people with Metastatic Pancreatic Ductal Adenocarcinoma, run by Novartis Pharmaceuticals at 31 sites in 14 countries.
Trial 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 previously untreated mPDAC. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Metastatic Pancreatic Ductal Adenocarcinoma
- What is being tested?
- NIS793, Spartalizumab and gemcitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 164 participants
- Where
- 31 sitesin 14 countries
- Study dates
- 16 Oct 2020to 2 May 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 13Show fewer
- 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.
Trial locations and contacts
31 sites in 14 countries.
31 sites in 14 countries
United States5 sites
Winship Cancer Institute
Atlanta, Georgia, 30322
Sidney Kimmel CCC At JH
Baltimore, Maryland, 21231
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Cente
Boston, Massachusetts, 02215
Univ of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15232
Italy4 sites
Novartis Investigative Site
Milan, MI, 20132
Novartis Investigative Site
Milan, MI, 20141
Novartis Investigative Site
Rozzano, MI, 20089
Novartis Investigative Site
Verona, VR, 37134
Germany3 sites
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Heidelberg, 69120
Novartis Investigative Site
Ulm, 89081
Spain3 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
Madrid, 28050
Australia2 sites
Novartis Investigative Site
Melbourne, Victoria, 3000
Novartis Investigative Site
Westmead, New South Wales, 2145
Austria2 sites
Novartis Investigative Site
Salzburg, 5020
Novartis Investigative Site
Vienna, A-1090
France2 sites
Novartis Investigative Site
Paris, 75475
Novartis Investigative Site
Toulouse, 31054
Singapore2 sites
Novartis Investigative Site
Singapore, 119074
Novartis Investigative Site
Singapore, 168583
Switzerland2 sites
Novartis Investigative Site
Sankt Gallen, 9007
Novartis Investigative Site
Zurich, 8091
Taiwan2 sites
Novartis Investigative Site
Taichung, 40447
Novartis Investigative Site
Taipei, 10002
About this study
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)
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 previously untreated mPDAC.
Read the detailed description
This is a randomized, parallel arms, open-label, multi-center, Phase II study to evaluate the efficacy and safety of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel in participants with first-line metastatic pancreatic ductal adenocarcinoma (mPDAC).
The study started with a Safety Run-in to assess the safety and tolerability of NIS793 in combination with spartalizumab and standard of care (SOC) gemcitabine/nab-paclitaxel. Doses defined for each study treatment, as part of this quadruplet were administered in the Randomized part in the quadruplet/triplet/doublet-based treatment arms.
The Randomized part opened after the Safety Run-in had completed. Participants were randomized in a 1:1:1 ratio to one of the three treatment arms:
- Arm 1: NIS793 with spartalizumab and gemcitabine/nab-paclitaxel
- Arm 2: NIS793 with gemcitabine/nab-paclitaxel
- Arm 3: gemcitabine/nab-paclitaxel
- Being tested
- NIS793, Spartalizumab, gemcitabine, nab-paclitaxel
- Keywords
- NIS793, spartalizumab, gemcitabine, nab-paclitaxel, mPDAC, TGFβ, PD-1, Phase II
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NIS793Biological
anti-TGFb antibody. NIS793 2100 mg every 2 weeks by intravenous (i.v.) infusion.
SpartalizumabBiological
Also called PDR001
anti-PD-1 antibody. spartalizumab 400 mg every 4 weeks by i.v. infusion.
gemcitabineDrug
SOC chemotherapy. Gemcitabine (1000 mg/m^2 on Days 1, 8, and 15) i.v. given as per label.
nab-paclitaxelDrug
Also called abraxane
SOC chemotherapy. Nab-paclitaxel (125 mg/m^2 on Days 1, 8, and 15) i.v. given as per label.
| Study group | Role | What they receive |
|---|---|---|
| Safety Run-in | Experimental | Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel Receives: Biological: NIS793; Biological: Spartalizumab; Drug: gemcitabine; Drug: nab-paclitaxel |
| Randomized Arm 1 | Experimental | Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel Receives: Biological: NIS793; Biological: Spartalizumab; Drug: gemcitabine; Drug: nab-paclitaxel |
| Randomized Arm 2 | Experimental | Combination of NIS793 + gemcitabine + nab-paclitaxel Receives: Biological: NIS793; Drug: gemcitabine; Drug: nab-paclitaxel |
| Randomized Arm 3 | Active comparator | gemcitabine + nab-paclitaxel Receives: Drug: gemcitabine; Drug: nab-paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety run-in Part: Number of Participants With Dose-Limiting Toxicities (DLTs)
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 where the relationship to study treatment cannot be ruled out and is not clearly related solely to disease, disease progression, inter-current illness or concomitant medications, which occurs within the DLT evaluation period. The DLT evaluation period is the first 28 days of treatment with NIS793 with spartalizumab in combination with gemcitabine/nab-paclitaxel. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
Measured: First cycle of treatment (28 days)
Safety run-in Part: Number of Participants With AEs and SAEs During the On-treatment Period
Number of participants with AEs (any adverse events regardless of seriousness) and serious adverse events (SAEs), including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs.
AE grades to characterize the severity of the AEs were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. For CTCAE v5.0, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE.
The on-treatment period is defined from the day of first administration of any study treatment up to 30 days after the date of the last actual administration of any study drug.
Measured: Up to approximately 0.8 years
Safety run-in Part: Number of Participants With Dose Reductions and Dose Interruptions of NIS793, Spartalizumab, Gemcitabine and Nab-paclitaxel
Number of participants with at least one dose reduction and at least one dose interruption of study drugs. Dose adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule.
No dose reductions were allowed for NIS793 and spartalizumab beyond the first 28 days period of Safety run-in part.
Measured: Up to approximately 0.7 years
Safety run-in Part: Dose Intensity of NIS793 and Spartalizumab
Dose intensity of NIS973 and spartalizumab was calculated as cumulative actual dose in milligrams divided by duration of exposure in days and multiplied by 28 days. Dose adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule.
Measured: Cycle 1 and Cycle 3. The duration of each cycle was 28 days.
Safety run-in Part: Dose Intensity of Gemcitabine and Nab-paclitaxel
Dose intensity of gemcitabine and nab-paclitaxel was calculated as cumulative actual dose in milligrams/m^2 divided by duration of exposure in days and multiplied by 28 days.
Measured: Cycle 1 and Cycle 3. The duration of each cycle was 28 days.
Randomized Part: Progression-Free Survival (PFS) Per RECIST v1.1 - Bayesian Model
PFS was based on local review of tumor assessments, using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. PFS is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. If a subject had not had an event, PFS was censored at the date of last adequate tumor assessment.
PFS was estimated using a Bayesian model. For each comparison (arm 1 versus arm 3 and arm 2 versus arm 3), PFS was modeled using a two-piece hazard model, with specifying hazard rates before and after the possible delayed effect for arms 1 and 2 and constant hazard rate for arm 3.
Results in the table as expressed as estimated posterior median hazard rate and one-sided 90% credible interval.
Measured: Up to approximately 2 years. Risk changing timepoint=approximately 0.3 years.
Randomized Part: Progression-Free Survival (PFS) Per RECIST v1.1 - Kaplan-Meier Curves and Cox Model
PFS was based on local review of tumor assessments, using RECIST 1.1 criteria. PFS is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. If a subject had not had an event, PFS was censored at the date of last adequate tumor assessment.
PFS was analyzed based on the Kaplan-Meier curves and the Cox model.
Measured: Up to approximately 2 years
Secondary outcomes (24)
Randomized Part: Number of Participants With AEs and SAEs During the On-treatment Period
Number of participants with AEs (any adverse events regardless of seriousness) and serious adverse events (SAEs), including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs.
AE grades to characterize the severity of the AEs were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. For CTCAE v5.0, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE.
The on-treatment period is defined from the day of first administration of any study treatment up to 30 days after the date of the last actual administration of any study drug.
Measured: Up to approximately 1.8 years
Randomized Part: Number of Participants With Dose Reductions and Dose Interruptions of NIS793, Spartalizumab, Gemcitabine and Nab-paclitaxel
Number of participants with at least one dose reduction and at least one dose interruption of study drugs. Dose adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule.
No dose reductions were allowed for NIS793 and spartalizumab in the Randomized part.
Measured: Up to approximately 1.7 years
Randomized Part: Dose Intensity of NIS973 and Spartalizumab
Dose intensity of NIS973 and spartalizumab was calculated as cumulative actual dose in milligrams divided by duration of exposure in days and multiplied by 28 days. Dose adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule.
Measured: Cycle 1 and Cycle 3. The duration of each cycle was 28 days
Randomized Part: Dose Intensity of Gemcitabine and Nab-paclitaxel
Dose intensity of gemcitabine and nab-paclitaxel was calculated as cumulative actual dose in milligrams/m^2 divided by duration of exposure in days and multiplied by 28 days.
Measured: Cycle 1 and Cycle 3. The duration of each cycle was 28 days
Randomized Part: Overall Response Rate (ORR) Per RECIST v1.1
ORR is the percentage of patients with a confirmed best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.
For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Measured: Up to approximately 1.7 years
Randomized Part: Duration of Response (DOR) Per RECIST v1.1
DOR per RECIST v1.1 is defined as the time from the first documented response of CR or PR to the date of the first documented progression or death. DOR only applies to patients with a best overall response of CR or PR by investigator assessment per RECIST v1.1. Participants continuing without progression or death were censored at the date of their last adequate tumor assessment.
DOR was analyzed using the Kaplan-Meier method.
Measured: Up to approximately 1.7 years
Randomized Part: Time to Progression (TTP) Per RECIST v1.1
TTP per RECIST v1.1 is defined as the time from the date of randomization to the date of event defined as the first documented progression per RECIST v1.1 or death due to underlying cancer. If a participant had no progression or death, the participant was censored at the date of last adequate tumor assessment.
DOR was analyzed using the Kaplan-Meier method.
Measured: Up to approximately 1.7 years
Randomized Part: Overall Survival (OS)
Overall survival is defined as the time from the date of randomization to the date of death due to any cause.
OS was analyzed using the Kaplan-Meier method.
Measured: Up to approximately 2 years
Randomized Part: Change From Baseline in PD-L1 Expression
The tumor expression of programmed cell death-ligand 1 (PD-L1) was measured by immunohistochemical methods. Results are expressed as absolute change from baseline in PD-L1 expression.
Measured: Baseline (Screening), on-treatment (anytime between Cycle 3 Day 2 and Day 4). The duration of each cycle was 28 days.
Randomized Part: Change From Baseline in CD8 Expression
The tumor expression of CD8 was measured by immunohistochemical methods. Results are expressed as absolute change from baseline in CD8 expression.
Measured: Baseline (Screening), on-treatment (anytime between Cycle 3 Day 2 and Day 4). The duration of each cycle was 28 days.
Randomized Part: Number of Participants With Anti-NIS793 Antibodies
The immunogenicity (IG) against NIS793 was assessed in serum using a validated enhanced electrochemiluminescence immunoassay (ECLIA).
Patient anti-drug antibodies (ADA) status was defined as follows:
- ADA-negative at baseline: ADA-negative sample at baseline
- ADA-positive at baseline: ADA-positive sample at baseline
- ADA-negative post-baseline: patient with ADA-negative sample at baseline and at least 1 post baseline sample, all of which are ADA-negative samples
- ADA-inconclusive post-baseline = patient who does not qualify as ADA-positive or ADA-negative post-baseline
- Treatment-induced ADA-positive = ADA-negative sample at baseline and at least 1 treatment-induced ADA-positive sample
Measured: Baseline (before first dose) and post-baseline (assessed throughout the treatment up to approximately 1.7 years)
Randomized Part: Number of Participants With Anti-spartalizumab Antibodies
The immunogenicity (IG) against spartalizumab was assessed in serum using a validated a validated homogenous enzyme-linked immunosorbent assay (ELISA).
Patient anti-drug antibodies (ADA) status was defined as follows:
- ADA-negative at baseline: ADA-negative sample at baseline
- ADA-inconclusive at baseline: patient who does not qualify as ADA-positive or ADA-negative at baseline
- ADA-positive at baseline: ADA-positive sample at baseline
- ADA-negative post-baseline: patient with ADA-negative sample at baseline and at least 1 post baseline sample, all of which are ADA-negative samples
- ADA-inconclusive post-baseline = patient who does not qualify as ADA-positive or ADA-negative post-baseline
- Treatment-induced ADA-positive = ADA-negative sample at baseline and at least 1 treatment-induced ADA-positive sample
Measured: Cycle 1 and Cycle 3. The duration of each cycle was 28 days
Randomized Part: Maximum Observed Serum Concentration (Cmax) of NIS793
Pharmacokinetic (PK) parameters were calculated based on NIS793 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed concentration following a dose.
Measured: 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
Randomized Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of NIS793
PK parameters were calculated based on NIS793 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
Measured: 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
Randomized Part: Trough Serum Concentration (Ctrough) of NIS793
Ctrough is defined as the concentration reached immediately before the next dose is administered. All drug concentrations below the lower limit of quantification were treated as zero for the calculation of PK parameters.
Measured: Cycle 1: pre-dose on Day 1. Cycle 3: pre-dose on Day 1 and Day 15 (combined). One cycle=28 days
Randomized Part: Maximum Observed Serum Concentration (Cmax) of Spartalizumab
PK parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed concentration following a dose.
Measured: 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
Randomized Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Spartalizumab
PK parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
Measured: 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
Randomized Part: Trough Serum Concentration (Ctrough) of Spartalizumab
Ctrough is defined as the concentration reached immediately before the next dose is administered. All drug concentrations below the lower limit of quantification were treated as zero for the calculation of PK parameters.
Measured: Cycle 2, 3 and 4: pre-dose on Day 1. One cycle=28 days
Randomized Part: Maximum Observed Plasma Concentration (Cmax) of Gemcitabine
PK parameters were calculated based on gemcitabine plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed concentration following a dose.
Measured: 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
Randomized Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Gemcitabine
PK parameters were calculated based on gemcitabine plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
Measured: 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
Randomized Part: Trough Serum Concentration (Ctrough) of Gemcitabine
Ctrough is defined as the concentration reached immediately before the next dose is administered. All drug concentrations below the lower limit of quantification were treated as zero for the calculation of PK parameters.
Measured: Cycle 4: pre-dose on Day 1. One cycle=28 days
Randomized Part: Maximum Observed Plasma Concentration (Cmax) of Nab-paclitaxel
PK parameters were calculated based on nab-paclitaxel plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed concentration following a dose.
Measured: 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
Randomized Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Nab-paclitaxel
PK parameters were calculated based on nab-paclitaxel plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
Measured: 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
Randomized Part: Trough Serum Concentration (Ctrough) of Nab-paclitaxel
Ctrough is defined as the concentration reached immediately before the next dose is administered. All drug concentrations below the lower limit of quantification were treated as zero for the calculation of PK parameters.
Measured: Cycle 4: pre-dose on Day 1. One cycle=28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2020
- Study start16 Oct 2020
- Primary completion26 Apr 2024
- Study completion2 May 2024
Why it stopped: The study was early terminated following the NIS793 treatment halt and urgent safety measure issued in July 2023, as the continued evaluation of Standard of Care alone will not support the original purpose of this phase 2 clinical trial.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Pancreatic Ductal AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 164 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04390763
- Sponsor's protocol ID
- CNIS793B12201
- Other IDs
- 2020-000349-14
- Acronym
- daNIS-1
- Status last verified
- Oct 2025
- First submitted
- 14 May 2020
- Last updated
- 16 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04390763
- Acronym / sponsor ID
- daNIS-1 / CNIS793B12201
- Keywords
- NIS793, spartalizumab, gemcitabine, nab-paclitaxel, mPDAC, TGFβ, PD-1, Phase II
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was early terminated following the NIS793 treatment halt and urgent safety measure issued in July 2023, as the continued evaluation of Standard of Care alone will not support the original purpose of this phase 2 clinical trial.
- Enrolment
- 164 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 16 Oct 2020 (actual)
- Primary completion
- 26 Apr 2024 (actual)
- Study completion
- 2 May 2024 (actual)
- First posted
- 18 May 2020 (actual)
- Results
- Posted 28 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 previously untreated mPDAC.
Detailed description
This is a randomized, parallel arms, open-label, multi-center, Phase II study to evaluate the efficacy and safety of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel in participants with first-line metastatic pancreatic ductal adenocarcinoma (mPDAC).
The study started with a Safety Run-in to assess the safety and tolerability of NIS793 in combination with spartalizumab and standard of care (SOC) gemcitabine/nab-paclitaxel. Doses defined for each study treatment, as part of this quadruplet were administered in the Randomized part in the quadruplet/triplet/doublet-based treatment arms.
The Randomized part opened after the Safety Run-in had completed. Participants were randomized in a 1:1:1 ratio to one of the three treatment arms:
- Arm 1: NIS793 with spartalizumab and gemcitabine/nab-paclitaxel
- Arm 2: NIS793 with gemcitabine/nab-paclitaxel
- Arm 3: gemcitabine/nab-paclitaxel
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Safety Run-in | Experimental | Biological: NIS793, Biological: Spartalizumab, Drug: gemcitabine, Drug: nab-paclitaxelCombination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel |
| Randomized Arm 1 | Experimental | Biological: NIS793, Biological: Spartalizumab, Drug: gemcitabine, Drug: nab-paclitaxelCombination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel |
| Randomized Arm 2 | Experimental | Biological: NIS793, Drug: gemcitabine, Drug: nab-paclitaxelCombination of NIS793 + gemcitabine + nab-paclitaxel |
| Randomized Arm 3 | Active comparator | Drug: gemcitabine, Drug: nab-paclitaxelgemcitabine + nab-paclitaxel |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NIS793anti-TGFb antibody. NIS793 2100 mg every 2 weeks by intravenous (i.v.) infusion. | Biological | Randomized Arm 1, Randomized Arm 2, Safety Run-in |
| SpartalizumabAlso: PDR001anti-PD-1 antibody. spartalizumab 400 mg every 4 weeks by i.v. infusion. | Biological | Randomized Arm 1, Safety Run-in |
| gemcitabineSOC chemotherapy. Gemcitabine (1000 mg/m^2 on Days 1, 8, and 15) i.v. given as per label. | Drug | Randomized Arm 1, Randomized Arm 2, Randomized Arm 3, Safety Run-in |
| nab-paclitaxelAlso: abraxaneSOC chemotherapy. Nab-paclitaxel (125 mg/m^2 on Days 1, 8, and 15) i.v. given as per label. | Drug | Randomized Arm 1, Randomized Arm 2, Randomized Arm 3, Safety Run-in |
Primary outcome
Safety run-in Part: Number of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: First cycle of treatment (28 days)
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 where the relationship to study treatment cannot be ruled out and is not clearly related solely to disease, disease progression, inter-current illness or concomitant medications, which occurs within the DLT evaluation period. The DLT evaluation period is the first 28 days of treatment with NIS793 with spartalizumab in combination with gemcitabine/nab-paclitaxel. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
Safety run-in Part: Number of Participants With AEs and SAEs During the On-treatment Period
Time frame: Up to approximately 0.8 years
Number of participants with AEs (any adverse events regardless of seriousness) and serious adverse events (SAEs), including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. AE grades to characterize the severity of the AEs were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. For CTCAE v5.0, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE. The on-treatment period is defined from the day of first administration of any study treatment up to 30 days after the date of the last actual administration of any study drug.
Safety run-in Part: Number of Participants With Dose Reductions and Dose Interruptions of NIS793, Spartalizumab, Gemcitabine and Nab-paclitaxel
Time frame: Up to approximately 0.7 years
Number of participants with at least one dose reduction and at least one dose interruption of study drugs. Dose adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule. No dose reductions were allowed for NIS793 and spartalizumab beyond the first 28 days period of Safety run-in part.
Safety run-in Part: Dose Intensity of NIS793 and Spartalizumab
Time frame: Cycle 1 and Cycle 3. The duration of each cycle was 28 days.
Dose intensity of NIS973 and spartalizumab was calculated as cumulative actual dose in milligrams divided by duration of exposure in days and multiplied by 28 days. Dose adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule.
Safety run-in Part: Dose Intensity of Gemcitabine and Nab-paclitaxel
Time frame: Cycle 1 and Cycle 3. The duration of each cycle was 28 days.
Dose intensity of gemcitabine and nab-paclitaxel was calculated as cumulative actual dose in milligrams/m^2 divided by duration of exposure in days and multiplied by 28 days.
Randomized Part: Progression-Free Survival (PFS) Per RECIST v1.1 - Bayesian Model
Time frame: Up to approximately 2 years. Risk changing timepoint=approximately 0.3 years.
PFS was based on local review of tumor assessments, using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. PFS is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. If a subject had not had an event, PFS was censored at the date of last adequate tumor assessment. PFS was estimated using a Bayesian model. For each comparison (arm 1 versus arm 3 and arm 2 versus arm 3), PFS was modeled using a two-piece hazard model, with specifying hazard rates before and after the possible delayed effect for arms 1 and 2 and constant hazard rate for arm 3. Results in the table as expressed as estimated posterior median hazard rate and one-sided 90% credible interval.
Randomized Part: Progression-Free Survival (PFS) Per RECIST v1.1 - Kaplan-Meier Curves and Cox Model
Time frame: Up to approximately 2 years
PFS was based on local review of tumor assessments, using RECIST 1.1 criteria. PFS is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. If a subject had not had an event, PFS was censored at the date of last adequate tumor assessment. PFS was analyzed based on the Kaplan-Meier curves and the Cox model.
24 secondary outcomes
Randomized Part: Number of Participants With AEs and SAEs During the On-treatment Period
Time frame: Up to approximately 1.8 years
Randomized Part: Number of Participants With Dose Reductions and Dose Interruptions of NIS793, Spartalizumab, Gemcitabine and Nab-paclitaxel
Time frame: Up to approximately 1.7 years
Randomized Part: Dose Intensity of NIS973 and Spartalizumab
Time frame: Cycle 1 and Cycle 3. The duration of each cycle was 28 days
Randomized Part: Dose Intensity of Gemcitabine and Nab-paclitaxel
Time frame: Cycle 1 and Cycle 3. The duration of each cycle was 28 days
Randomized Part: Overall Response Rate (ORR) Per RECIST v1.1
Time frame: Up to approximately 1.7 years
Randomized Part: Duration of Response (DOR) Per RECIST v1.1
Time frame: Up to approximately 1.7 years
Randomized Part: Time to Progression (TTP) Per RECIST v1.1
Time frame: Up to approximately 1.7 years
Randomized Part: Overall Survival (OS)
Time frame: Up to approximately 2 years
Randomized Part: Change From Baseline in PD-L1 Expression
Time frame: Baseline (Screening), on-treatment (anytime between Cycle 3 Day 2 and Day 4). The duration of each cycle was 28 days.
Randomized Part: Change From Baseline in CD8 Expression
Time frame: Baseline (Screening), on-treatment (anytime between Cycle 3 Day 2 and Day 4). The duration of each cycle was 28 days.
Randomized Part: Number of Participants With Anti-NIS793 Antibodies
Time frame: Baseline (before first dose) and post-baseline (assessed throughout the treatment up to approximately 1.7 years)
Randomized Part: Number of Participants With Anti-spartalizumab Antibodies
Time frame: Cycle 1 and Cycle 3. The duration of each cycle was 28 days
Randomized Part: Maximum Observed Serum Concentration (Cmax) of NIS793
Time frame: 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
Randomized Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of NIS793
Time frame: 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
Randomized Part: Trough Serum Concentration (Ctrough) of NIS793
Time frame: Cycle 1: pre-dose on Day 1. Cycle 3: pre-dose on Day 1 and Day 15 (combined). One cycle=28 days
Randomized Part: Maximum Observed Serum Concentration (Cmax) of Spartalizumab
Time frame: 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
Randomized Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Spartalizumab
Time frame: 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
Randomized Part: Trough Serum Concentration (Ctrough) of Spartalizumab
Time frame: Cycle 2, 3 and 4: pre-dose on Day 1. One cycle=28 days
Randomized Part: Maximum Observed Plasma Concentration (Cmax) of Gemcitabine
Time frame: 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
Randomized Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Gemcitabine
Time frame: 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
Randomized Part: Trough Serum Concentration (Ctrough) of Gemcitabine
Time frame: Cycle 4: pre-dose on Day 1. One cycle=28 days
Randomized Part: Maximum Observed Plasma Concentration (Cmax) of Nab-paclitaxel
Time frame: 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
Randomized Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Nab-paclitaxel
Time frame: 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
Randomized Part: Trough Serum Concentration (Ctrough) of Nab-paclitaxel
Time frame: Cycle 4: pre-dose on Day 1. One cycle=28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
31 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NIS793, Spartalizumab and gemcitabine in people with Metastatic Pancreatic Ductal Adenocarcinoma, run by Novartis Pharmaceuticals at 31 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 31 sites in United States, Italy, Germany, Spain, Australia and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety run-in Part: Number of Participants With Dose-Limiting Toxicities (DLTs) (time frame: First cycle of treatment (28 days)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2025.