Phase 3
N=511
Study of Efficacy and Safety of NIS793 in Combination With Standard of Care (SOC) Chemotherapy in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) - daNIS-2
Metastatic Pancreatic Ductal Adenocarcinoma
Bottom Line
View on ClinicalTrials.gov: NCT04935359 ↗Enrolled (actual)
511
Serious AEs
34.9%
Results posted
May 2026
Primary outcome: Primary: Safety run-in Part: Percentage of Participants With Dose Limiting Toxicities (DLTs) During the First Cycle (4 Weeks) of Treatment. — 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- NIS793 (Drug); Nab-paclitaxel (Drug); Gemcitabine (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Aug 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Safety run-in Part: Percentage of Participants With Dose Limiting Toxicities (DLTs) During the First Cycle (4 Weeks) of Treatment. |
— | — |
| PRIMARY Randomized Part: Overall Survival (OS) |
9.2; 11.2 | — |
| SECONDARY Percentage of Participants With Adverse Events (AEs) |
21; 239; 239; 13; 144; 110 | — |
| SECONDARY Percentage of Participants With Dose Interruptions and Dose Reductions of NIS793 in Combination With Gemcitabine and Nab-paclitaxel |
5; 92; 82; 16; 147; 159 | — |
| SECONDARY Dose Intensity of NIS793 in Combination With Gemcitabine and Nab-paclitaxel |
3669.2; 3134.1; 3183.4 | — |
| SECONDARY Progression-Free Survival (PFS) |
5.4; 4.6; 5.4 | — |
| SECONDARY Overall Response Rate (ORR) |
19.0; 21.6; 25.3 | — |
| SECONDARY Disease Control Rate (DCR) |
76.2; 66.9; 72.2 | — |
| SECONDARY Duration of Response (DOR) |
8.6; 6.2; 5.6 | — |
| SECONDARY Time to Response (TTR) |
NA; NA; NA | — |
| SECONDARY Safety run-in Part: Trough Concentration (Ctrough) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel |
230000; 207000; 300000; 309000; 370000; 425000 | — |
| SECONDARY Safety run-in Part: Maximum Concentration (Cmax) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel |
549000; 837000 | — |
| SECONDARY Safety run-in Part: Time to Reach Maximum Concentration (Tmax) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel |
1.12; 0.883 | — |
| SECONDARY Randomized Part (Chinese Participants With Intensive PK Sampling): Trough Concentration (Ctrough) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel |
149000; 366000; 380000; 371000; 493000 | — |
| SECONDARY Randomized Part (Chinese Participants With Intensive PK Sampling): Maximum Concentration (Cmax) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel |
691000; 978000 | — |
| SECONDARY Randomized Part (Chinese Participants With Intensive PK Sampling): Time to Reach Maximum Concentration (Tmax) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel |
1.52; 3.98 | — |
| SECONDARY Randomized Part (Chinese Participants With Intensive PK Sampling): Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel |
48900000 | — |
| SECONDARY Randomized Part (Chinese Participants With Intensive PK Sampling): Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel |
159000000 | — |
| SECONDARY Randomized Part (Participants Without Intensive PK Sampling): Trough Concentration (Ctrough) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel |
249000; 331000; 335000; 334000; 302000 | — |
| SECONDARY Randomized Part (Participants Without Intensive PK Sampling): Maximum Concentration (Cmax) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel |
625000; 807000 | — |
| SECONDARY Randomized Part (Participants Without Intensive PK Sampling): Time to Reach Maximum Concentration (Tmax) of NIS793 in Combination With Gemcitabine and Nab-paclitaxel |
1.08; 0.833 | — |
| SECONDARY Randomized Part: Anti-drug Antibodies (ADA) Against NIS793 Prevalence at Baseline |
196; 0 | — |
| SECONDARY Randomized Part: Anti-drug Antibodies (ADA) Against NIS793 Incidence on Treatment |
0; 0; 196 | — |
Summary
The purpose of this study was to evaluate the efficacy and safety of NIS793 in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel and placebo in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC). This study aimed to explore whether blockade of Transforming Growth Factor β (TGFβ) in combination with gemcitabine/nab-paclitaxel could reduce fibrosis in PDAC, restore chemo-sensitivity and ultimately lead to improvements in overall survival (OS) and other clinically relevant outcomes.
Eligibility Criteria
Key Inclusion Criteria
Applicable for both Safety run-in and Randomized part
- Participants aged ≥18 years with histologically or cytologically confirmed (based on local assessment and per local guidelines) mPDAC eligible for treatment in the first line setting and not amenable for potentially curative surgery
- Presence of at least one measurable lesion assessed by Computerized Tomography (CT) and/or Magnetic Resonance Imaging (MRI) according to RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
- Adequate organ function (assessed by central laboratory for eligibility)
- Participants must have recovered from treatment-related toxicities of prior anticancer therapies to grade ≤ 1 (CTCAE v 5.0) at time of screening, except alopecia.
Key Main Exclusion Criteria:
Applicable for both Safety run-in and Randomized part
- Previous systemic anti-cancer treatment for metastatic PDAC
- Pancreatic neuroendocrine (islet) or acinar tumors
- Participants with known status of microsatellite instability-high (MSI-H) or mismatch repair-deficient pancreatic cancer (if status is not already available, testing is not required at screening).
- Participant has not recovered from a major surgery performed prior to start of study treatment or has had a major surgery within 4 weeks prior to start of study treatment.
- Radiation therapy or brain radiotherapy ≤ 4 weeks prior to start of study treatment (palliative radiotherapy to bone lesions allowed > 2 weeks prior to start of study treatment).
- Impaired cardiac function or clinically significant cardio-vascular disease
- Use of hematopoietic growth factors or transfusion support ≤ 2 weeks prior to start of study treatment.
- Participant has conditions that are considered to have a high risk of clinically significant gastrointestinal tract bleeding or any other condition associated with or history of significant bleeding.
- Serious non-healing wounds.
- Pregnant or breast-feeding women
- Women of childbearing potential, unless willing to use highly effective contraception methods during treatment and after stopping study treatments as indicated
- Pre-existing peripheral neuropathy > grade 1 (CTCAE v5.0)
Other Inclusion/Exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT04935359). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.