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 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: CNIS793B122012020-000349-14
• Study Type: interventional
• Target: 164
• Locations: 13 countries
• Sites: 29

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 previously untreated mPDAC.

Conditions

Metastatic Pancreatic Ductal Adenocarcinoma

Keywords

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

Outcome Measures

Primary Outcomes (7)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  Up to approximately 2 years

Secondary Outcomes (24)

• Randomized Part: Number of Participants With AEs and SAEs During the On-treatment Period

  Up to approximately 1.8 years

• Randomized Part: Number of Participants With Dose Reductions and Dose Interruptions of NIS793, Spartalizumab, Gemcitabine and Nab-paclitaxel

  Up to approximately 1.7 years

• Randomized Part: Dose Intensity of NIS973 and Spartalizumab

  Cycle 1 and Cycle 3. The duration of each cycle was 28 days

• Randomized Part: Dose Intensity of Gemcitabine and Nab-paclitaxel

  Cycle 1 and Cycle 3. The duration of each cycle was 28 days

• Randomized Part: Overall Response Rate (ORR) Per RECIST v1.1

  Up to approximately 1.7 years

Study Arms (4)

Safety Run-in

EXPERIMENTAL

Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel

Biological: NIS793; Biological: Spartalizumab; Drug: gemcitabine; Drug: nab-paclitaxel

Randomized Arm 1

EXPERIMENTAL

Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel

Biological: NIS793; Biological: Spartalizumab; Drug: gemcitabine; Drug: nab-paclitaxel

Randomized Arm 2

EXPERIMENTAL

Combination of NIS793 + gemcitabine + nab-paclitaxel

Biological: NIS793; Drug: gemcitabine; Drug: nab-paclitaxel

Randomized Arm 3

ACTIVE COMPARATOR

gemcitabine + nab-paclitaxel

Drug: gemcitabine; Drug: nab-paclitaxel

Interventions

NIS793 BIOLOGICAL

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

Randomized Arm 1; Randomized Arm 2; Safety Run-in

Spartalizumab BIOLOGICAL

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

Also known as: PDR001

Randomized Arm 1; Safety Run-in

gemcitabine DRUG

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

Randomized Arm 1; Randomized Arm 2; Randomized Arm 3; Safety Run-in

nab-paclitaxel DRUG

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

Also known as: abraxane

Randomized Arm 1; Randomized Arm 2; Randomized Arm 3; Safety Run-in

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (31)

Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Sidney Kimmel CCC At JH

Baltimore, Maryland, 21231, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Cente

Boston, Massachusetts, 02215, United States

Location

Univ of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Novartis Investigative Site

Westmead, New South Wales, 2145, Australia

Location

Novartis Investigative Site

Melbourne, Victoria, 3000, Australia

Location

Novartis Investigative Site

Salzburg, 5020, Austria

Location

Novartis Investigative Site

Vienna, A-1090, Austria

Location

Novartis Investigative Site

Liège, 4000, Belgium

Location

Novartis Investigative Site

Brno, Czech Republic, 656 53, Czechia

Location

Novartis Investigative Site

Helsinki, FIN-00029, Finland

Location

Novartis Investigative Site

Paris, 75475, France

Location

Novartis Investigative Site

Toulouse, 31054, France

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

Novartis Investigative Site

Milan, MI, 20132, Italy

Location

Novartis Investigative Site

Milan, MI, 20141, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Verona, VR, 37134, Italy

Location

Novartis Investigative Site

Singapore, 119074, Singapore

Location

Novartis Investigative Site

Singapore, 168583, Singapore

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

Madrid, 28050, Spain

Location

Novartis Investigative Site

Sankt Gallen, 9007, Switzerland

Location

Novartis Investigative Site

Zurich, 8091, Switzerland

Location

Novartis Investigative Site

Taichung, 40447, Taiwan

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Novartis Investigative Site

Oxford, OX3 7LE, United Kingdom

Location

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Interventions

NIS-793; spartalizumab; Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2020
• First Posted: May 18, 2020
• Study Start: October 16, 2020
• Primary Completion: April 26, 2024
• Study Completion: May 2, 2024
• Last Updated: October 16, 2025
• Results First Posted: May 28, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

SG (2); FR (2); CH (2); TW (2); IT (4); AU (2); DE (3); ES (3); GB (1); US (5); CZ (1); FI (1); BE (1)