Study to investigate NIS793 (with or without Spartalizumab) in combination with chemotherapy in patients with metastatic pancreatic cancer

Australia, Austria, Belgium, Canada, Czech Republic, Finland, France, Germany, Italy, Japan, Singapore, Spain, Switzerland, Taiwan, United Kingdom, United States (ICTRP)

ICTRP Trial ID
EUCTR2020-000349-14 (ICTRP)

Official title (approved by ethics committee)
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) (BASEC)

Academic 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) (ICTRP)

Public title
Study of NIS793 (with and without spartalizumab) in combination with standard of care chemotherapy in previously untreated metastatic pancreatic cancer patients (ICTRP)

Disease under investigation
Pancreatic ductal adenocarcinoma
MedDRA version: 21.0Level: LLTClassification code 10033604Term: Pancreatic cancerSystem Organ Class: 100000004864;Therapeutic area: Diseases [C] - Cancer [C04] (ICTRP)

Intervention under investigation

Product Code: NIS793
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Not yet defined
Current Sponsor code: NIS793
Other descriptive name: NIS793
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Name: Spartalizumab
Product Code: PDR001
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Spartalizumab
Current Sponsor code: PDR001
Other descriptive name: PDR001
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Product Name: nab-paclitaxel
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Paclitaxel
CAS Number: 33069-62-4
Other descriptive name: PACLITAXEL ALBUMIN-BOUND
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Product Name: gemcitabine
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: GEMCITABINE
CAS Number: 95058-81-4
Other descriptive name: gemcitabine
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-

(ICTRP)

Type of trial
Interventional clinical trial of medicinal product (ICTRP)

Trial design
Controlled: no Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 4 (ICTRP)

Inclusion/Exclusion criteria
Gender:
Female: yes
Male: yes

Inclusion criteria:
Participants with histologically or cytologically confirmed treatment na?ve metastatic adenocarcinoma of the pancreas with measurable disease per RECIST 1.1.
Participants must have a site of disease amenable to biopsy, be candidate for tumor biopsy, and must be willing to undergo a tumor biopsy at screening and during therapy on the study.
ECOG performance status = 1
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 62
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 94
(ICTRP)

Exclusion criteria:
Previous radiotherapy, surgery (note: placement of biliary stent is allowed), chemotherapy or investigational therapy for the treatment of metastatic disease. Participants having received previous chemotherapy in the adjuvant setting
Participants with MSI-H pancreatic adenocarcinoma
Participants with a diagnosis of pancreatic neuroendocrine tumors (NETs), acinar, or islet cell tumors
Participants amenable to potentially curative resection
Presence of symptomatic CNS metastases or CNS metastases that require local CNS-directed therapy
History of severe hypersensitivity reactions to other monoclonal antibodies
Malignant disease other than that being treated in the study
Systemic chronic steroid therapy (>10mg/day prednisone or equivalent) or any immunosuppressive therapy
Known history of testing positive for HIV infection
Active HBV and HCV infection
Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment
Active, known or suspected autoimmune disease
History of or current pneumonitis or interstitial lung disease


Primary and secondary end points
Main Objective: Safety Run-in part:
? To assess the safety and tolerability of NIS793 with spartalizumab in combination with gemcitabine/nab-paclitaxel.

Randomized part:
? To evaluate the Progression Free Survival (PFS) per Investigator assessment of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus SOC chemotherapy gemcitabine/nab-paclitaxel.
? To evaluate the PFS of NIS793 with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel
;Secondary Objective: Randomized part:
? To evaluate the safety and tolerability of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel
? To assess the preliminary anti-tumor activity of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel
? To assess Overall Survival (OS) of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel
? To assess the CD8 and PD-L1 status of the participants at screening and on treatment versus gemcitabine/nab-paclitaxel
? To characterize the incidence of immunogenicity of NIS793 and spartalizumab in combination with gemcitabine/nab-paclitaxel
? To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)
;Primary end point(s): Safety Run-in part:
1) Incidence of DLTs during the first 4 weeks of treatment
2) Safety: Incidence and severity of treatment emergent AEs and SAEs, changes between baseline and post-baseline laboratory parameters, vital signs, and ECG parameters
3) Tolerability: Dose interruptions, reductions and dose intensity

Randomized part:
4) Progression-free survival based on Response Evaluation Criteria in Solid Tumors (RECIST1.1) as per local Investigator?s review;Timepoint(s) of evaluation of this end point: 1) DLT observation period 4 weeks
2), 3), 4) end of study (ICTRP)

Secondary end point(s): Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs and ECGs, dose interruptions, reductions, and dose intensity
Overall response rate (ORR), Duration of response (DOR), Time to Progression (TTP) RECIST 1.1 as per local Investigator?s review
Overall Survival (OS)
Change from baseline in CD8 and PD-L1 IHC related markers
Antidrug antibodies (ADA) prevalence at baseline and ADA incidence on-treatment (anti-NIS793 and anti-spartalizumab)
Pharmacokinetic parameters (e.g. Ctrough, Cmax, AUClast)
PK concentration time profiles
;Timepoint(s) of evaluation of this end point: as per protocol Table 8-1 (ICTRP)

Registration date
16.07.2020 (ICTRP)

Incorporation of the first participant
09.11.2020 (ICTRP)

Secondary sponsors
not available

Additional contacts
Information&Communication M?dicales, icm.phfr@novartis.com, +33 1 5547 6600, Novartis Pharma S.A.S (ICTRP)

Secondary trial IDs
CNIS793B12201, 2020-000349-14-FI (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-000349-14 (ICTRP)