Study of NIS793 or placebo in combination with gemcitabine and nab-paclitaxel in participants with metastatic ductal adenocarcinoma of the pancreas (mPDAC)

Argentina, Australia, Belgium, Brazil, Canada, China, Czechia, Finland, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Norway, Russian Federation, Singapore, Slovakia, Spain, Sweden, Switzerland, Taiwan, Turkey, United Kingdom, United States (ICTRP)

ICTRP Trial ID
EUCTR2021-000591-10 (ICTRP)

Official title (approved by ethics committee)
A randomized, double-blind, phase III study comparing NIS793 in combination with gemcitabine and nab-paclitaxel versus placebo combined with gemcitabine and nab-paclitaxel for first line treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC) (BASEC)

Academic title
A randomized, double-blind, phase III study comparing NIS793 in combination with gemcitabine and nab-paclitaxel versus placebo combined with gemcitabine and nab-paclitaxel for first line treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC) (ICTRP)

Public title
Study of efficacy and safety of NIS793 in combination with standard of care (SOC) chemotherapy in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) (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: NIS793Pharmaceutical Form: Concentrate for solution for infusionINN or Proposed INN: not yet definedCurrent Sponsor code: NIS793Other descriptive name: NIS793Concentration unit: mg/ml milligram(s)/millilitreConcentration type: equalConcentration number: 100-Pharmaceutical form of the placebo: Solution for infusionRoute of administration of the placebo: Intravenous useProduct Name: PazenirPharmaceutical Form: Powder for solution for infusionINN or Proposed INN: PaclitaxelCAS Number: 33069-62-4Other descriptive name: PACLITAXEL ALBUMIN-BOUNDConcentration unit: mg/ml milligram(s)/millilitreConcentration type: equalConcentration number: 5-Product Name: GEMCITABINE SANDOZPharmaceutical Form: Powder for solution for infusionINN or Proposed INN: GEMCITABINECAS Number: 95058-81-4Other descriptive name: gemcitabineConcentration unit: mg milligram(s)Concentration type: equalConcentration number: 40- (ICTRP)

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

Trial design
Controlled: yesRandomised: yesOpen: noSingle blind: noDouble blind: yesParallel group: yesCross over: noOther: noIf controlled, specify comparator, Other Medicinial Product: noPlacebo: yesOther: noNumber of treatment arms in the trial: 3 (ICTRP)

Inclusion/Exclusion criteria
Gender: Female: yesMale: yes
Inclusion criteria: Participants eligible must meet all of the following criteria: 1. signed ICF prior to study treatment2. age >= 18 years at the time of ICF3. histologically or cytologically confirmed mPDAC eligible for treatment in first line setting and not amenable for potentially curative surgery4. presence of at least one measurable lesion assessed by CT and/or MRI according to RECIST 1.15. ECOG performance status 0-16. adequate organ function as defined by the following laboratory values: - ANC >= 1.5 x 10*9 /L- platelets >= 100 x 10*9/L- hemoglobin >= 9g /dL- calculated creatinine clearance >= 60 mL/min- albumin >= 3 g/dL- PT/INR and PTT <= 1.5 x ULN- total bilirubin <= 1.5 X ULN- AST and/or ALT <= 3.0 x ULN7. WCBP must have negative pregnancy test during screening and before starting study treatment8. able to adhere to study visit schedule and other protocol requirements9. must have recovered from treatment-related toxicities of prior anticancer therapies to grade <= 1 (CTCAE v 5.0), except alopeciaAre the trial subjects under 18? noNumber of subjects for this age range: F.1.2 Adults (18-64 years) yesF.1.2.1 Number of subjects for this age range 200F.1.3 Elderly (>=65 years) yesF.1.3.1 Number of subjects for this age range 290 (ICTRP)

Exclusion criteria: participants meeting any of the following criteria are not eligible for inclusion:1. previous systemic anti-cancer treatment for mPDAC2. pancreatic neuroendocrine, acinar or inslet tumors3. known status of MSI-H or MMR-deficient pancreatic cancer4. presence of symptomatic CNS metastases, or CNS metastases that requires direct therapy or increasing doses of corticosteroids 2 weeks prior to study entry5. known history of severe allergy or hypersensitivity to any of the study drug or their excipients6. currently receiving any of the prohibited medications which cannot be discontinued within >= 7 days or 5 half-lifes, whichever is longer7. not recovered from a major surgery or has a major surgery within 4 weeks prior to start of the study8. radiation therapy or brain radiotherapy <= 4 weeks prior to study start9. impaired cardiac function or clinically significant cardio-vascular disease, such as: - congestive heart failure requiring treatment (NYHA grade >= 2), or clinically significant arrhythmia- acute myocardial infarction, unstable angina pectoris, coronary stenting or bypass surgery < 3 months prior to study entry- LVEF < 50%- elevated cardiac enzymes (troponin I) > 2 x ULN- cardiac valvulopathy >= grade 2- uncontrolled hypertension10. history of positive test for HIV infection11. active or chronic HBV or HCV infections12. active untreated or uncontrolled systemic fungal, bacterial or viral infections13. use of hematopoietic growth factors or transfusion support <= 2 weeks prior to start the study14. conditions that are considered to have a high risk of clinically significant gastrointestinal track bleeding or any other condition associated with or history of significant bleeding15. serious, non-healing wounds16. pre-existing peripheral neuropathy > grade 117. concurrent malignancy other than disease under treatment18. any significant medical condition, laboratory abnormality or psychiatric or social condition that would constitute unacceptable risk to the patients, contraindicate participation, limit patient's ability to comply with study requirements or compromise patient's compliance with the study protocol 19. pregnant or breast-feeding woman 20. WCBP, unless using highly effective method of contraception during and up to 90 days after the study drug treatment (NIS793)21. currently receiving other anti-cancer therapy or received other investigational product within 30 days or 5 half-lives prior to study treatment, whichever is longer

Primary and secondary end points
Main Objective: safety run in: to confirm the recommended phase 3 dose (RP3D) of NIS793 in combination with gemcitabine and nab-paclitaxel
randomized part: to compare OS in participants with mPDAC treated as the first line treatment with the combination of NIS793, gemcitabine and nab-paclitaxel to the combination of placebo with gemcitabine and nab-paclitaxel;Secondary Objective: safety run in:
1. safety and tolerability of NIS793 in combination with SoC
2. PK of NIS793 in combination with SoC
3. preliminary anti-tumor activity of NIS793 in combination with SoC

randomized part:
1. efficacy (PFS, ORR, DCR; DOR, TTR) of NIS793 in combination with SoC versus placebo in combination with SoC
2. safety and tolerability in each treatment arm
3. health-related QoL and other PROs in each treatment arm;Primary end point(s): safety run in: incidence of DLTs in the first cycle
randomized part: OS;Timepoint(s) of evaluation of this end point: safety run in: 4 weeks of treatment
randomized part: at participants' death (ICTRP)

Secondary end point(s): safety run in: 1. safety: incidence and severity of AEs2. tolerability: dose interruptions, dose reductions, dose intensity3. PK parameters for NIS793 in combination with SoC4. PFS, ORR, DCR, DOR, TTRrandomized part: 1. PFS, ORR, DCR, DOR, TTR2. incidence and severity of AEs and SAEs, dose interruptions, dose reductions3. change from baseline of individual domain scores in the PROMIS-29 profile and EQ-5D-5L at week 124. time to deterioration ;Timepoint(s) of evaluation of this end point: safety run in:1-3. first 4 weeks of treatment4. end of studyrandomized partat protocol defined timepoints (12 weeks)end of study (ICTRP)

Registration date
14.09.2021 (ICTRP)

Incorporation of the first participant
15.12.2021 (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
CNIS793B12301, 2021-000591-10-HU (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-000591-10 (ICTRP)