Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT04390763
Other study ID # CNIS793B12201
Secondary ID 2020-000349-14
Status Terminated
Phase Phase 2
First received
Last updated
Start date October 16, 2020
Est. completion date May 2, 2024

Study information

Verified date May 2024
Source Novartis
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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 untreated mPDAC.


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


Recruitment information / eligibility

Status Terminated
Enrollment 164
Est. completion date May 2, 2024
Est. primary completion date April 26, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
NIS793
anti-TGFb antibody
Spartalizumab
anti-PD-1 antibody
Drug:
gemcitabine
SOC chemotherapy
nab-paclitaxel
SOC chemotherapy

Locations

Country Name City State
Australia Novartis Investigative Site Melbourne Victoria
Australia Novartis Investigative Site Westmead New South Wales
Austria Novartis Investigative Site Salzburg
Austria Novartis Investigative Site Wien
Belgium Novartis Investigative Site Liege
Czechia Novartis Investigative Site Brno Czech Republic
Finland Novartis Investigative Site Helsinki
France Novartis Investigative Site Paris 10
France Novartis Investigative Site Toulouse 4
Germany Novartis Investigative Site Essen
Germany Novartis Investigative Site Heidelberg
Germany Novartis Investigative Site Ulm
Italy Novartis Investigative Site Milano MI
Italy Novartis Investigative Site Milano MI
Italy Novartis Investigative Site Rozzano MI
Italy Novartis Investigative Site Verona VR
Singapore Novartis Investigative Site Singapore
Singapore Novartis Investigative Site Singapore
Spain Novartis Investigative Site Barcelona Catalunya
Spain Novartis Investigative Site Barcelona Catalunya
Spain Novartis Investigative Site Madrid
Switzerland Novartis Investigative Site St. Gallen
Switzerland Novartis Investigative Site Zurich
Taiwan Novartis Investigative Site Taichung
Taiwan Novartis Investigative Site Taipei
United Kingdom Novartis Investigative Site Oxford
United States Winship Cancer Institute Main Centre Atlanta Georgia
United States Sidney Kimmel CCC At JH Baltimore Maryland
United States Beth Israel Deaconess Medical Cente Boston Massachusetts
United States Massachusetts General Hospital Massachusetts General Hospital Boston Massachusetts
United States Univ of Pittsburgh Cancer Institute HIllman Cancer Center Pittsburgh Pennsylvania

Sponsors (1)

Lead Sponsor Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Czechia,  Finland,  France,  Germany,  Italy,  Singapore,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 4 weeks
Primary 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.
8 months
Primary 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 8 months
Primary 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 8 months
Primary 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 18 months
Secondary 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.
18 months
Secondary Dose interruption/reduction in Randomized part 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 18 months
Secondary Dose intensity in Randomized part 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 18 months
Secondary 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 18 months
Secondary 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 18 months
Secondary 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 18 months
Secondary 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 18 months
Secondary 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 18 months
Secondary 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 18 months
Secondary 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) 12 months
Secondary 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) 12 months
Secondary Pharmacokinetic parameter Ctrough To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel) 12 months
See also
  Status Clinical Trial Phase
Active, not recruiting NCT04935359 - 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 Phase 3
Active, not recruiting NCT05095064 - Retrospective Study on the Efficacy and Tolerability of Liposomal Irinotecan
Active, not recruiting NCT05039177 - A Study of ERAS-007 in Patients With Advanced Gastrointestinal Malignancies Phase 1/Phase 2
Recruiting NCT04888312 - Safety and Efficacy of Mitazalimab in Combination With Chemotherapy in Pancreatic Cancer Patients Phase 1/Phase 2
Not yet recruiting NCT06206876 - FL118 for Treating Patients With Advanced Pancreatic Ductal Adenocarcinoma Phase 1
Recruiting NCT05642962 - Pancrelipase in People With Pancreatic Ductal Adenocarcinoma (PDAC) Phase 1/Phase 2
Completed NCT02501902 - Dose-Escalation Study Of Palbociclib + Nab-Paclitaxel In mPDAC Phase 1
Active, not recruiting NCT04581343 - A Phase 1B Study of Canakinumab, Spartalizumab, Nab-paclitaxel, and Gemcitabine in Metastatic PC Patients Phase 1
Completed NCT02558894 - Phase II Study of MEDI4736 Monotherapy or in Combinations With Tremelimumab in Metastatic Pancreatic Ductal Carcinoma Phase 2
Terminated NCT02732938 - Ph1b/2 Study of PF-04136309 in Combination With Gem/Nab-P in First-line Metastatic Pancreatic Patients Phase 2
Recruiting NCT05472259 - A Study Evaluating the Efficacy of 5-FU + NALIRI and 5-FU + NALIRINOX for PDAC (NALPAC) Phase 2
Recruiting NCT06445062 - Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors Phase 1/Phase 2
Recruiting NCT02600949 - Personalized Peptide Vaccine in Treating Patients With Advanced Pancreatic Cancer or Colorectal Cancer Phase 1
Recruiting NCT05630183 - A Study of Botensilimab in Participants With Metastatic Pancreatic Cancer Phase 2
Completed NCT02583477 - Phase Ib/II Study of MEDI4736 Evaluated in Different Combinations in Metastatic Pancreatic Ductal Carcinoma Phase 1/Phase 2
Terminated NCT04329949 - Study of Relacorilant in Combination With Nab-Paclitaxel in Patients With Metastatic Pancreatic Ductal Adenocarcinoma Phase 3
Terminated NCT02101021 - Gemcitabine and Nab-paclitaxel Combined With Momelotinib in Participants With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma Phase 3
Suspended NCT05685602 - CA-4948 Added to Standard Chemotherapy to Treat Metastatic or Unresectable Pancreatic Cancer Phase 1
Not yet recruiting NCT06398587 - Onvansertib in Combination With Gemcitabine and Nab-paclitaxel for the Treatment of Patients With Locally-advanced, Unresectable, or Metastatic Pancreatic Ductal Adenocarcinoma Phase 2
Completed NCT04990037 - A Study of the Safety and Tolerance of CAN04 in Combination With FOLFIRINOX in Subjects With Metastatic Pancreatic Ductal Adenocarcinoma Phase 1