metastatic colorectal cancer (mCRC) MedDRA version: 21.0 Level: PT Classification code 10061451 Term: Colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 27.0 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: NIS793
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: not yet available
Current Sponsor code: NIS793
Other descriptive name: NIS793
Concentration unit: m
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent must be obtained prior to participation in the study. 2. Age 18 years (or older, if required by local regulations) at the time of informed consent. 3. Histologically or cytologically confirmed (by local laboratory and local clinical guidelines) metastatic colorectal adenocarcinoma that is not amenable to potentially curative surgery in the opinion of the investigator and progressed on or within 6 months after the last dose of one prior line of systemic anti-cancer therapy administered for metastatic disease. 4. Presence of at least one measurable lesion assessed by CT and/or MRI according to RECIST 1.1. 5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1. 6. Adequate organ function as defined by the following laboratory values (assessed by central laboratory for eligibility except where indicated): • Absolute neutrophil count = 1.5 × 109/L • Platelets count = 100 × 109/L • Hemoglobin = 9 g/dL • Calculated creatinine clearance = 60 mL/min (e.g. by using Cockcroft-Gault equation) • Albumin = 3 g/dL • PT/INR and PTT = 1.5 x ULN. Participants requiring therapeutic anticoagulants are eligible if coagulation parameters are within therapeutic range. • Total bilirubin = 1.5 X ULN • Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase /serum glutamic pyruvic transaminase (ALT/SGPT) = 3.0 x ULN (=5 x ULN in presence of liver metastasis). In participants with elevated ALT or AST, the values must be stable for at least 2 weeks and with no evidence of biliary obstruction by imaging. 7. Women of child-bearing potential must have negative pregnancy tests during the screening period and before starting study treatment. 8. Able to adhere to study visit schedule and other protocol requirements. 9. Participant must have recovered from treatment related toxicities of prior anticancer therapies to grade =1 (CTCAE v5.0) at the time of screening, except alopecia. 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 164 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 102
Exclusion criteria
Exclusion criteria: 1.Previously administered of anti-cancer immunotherapy or TGF-ß targeted therapies 2.Microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) &/or BRAFV600 mutation positive colorectal cancer (tests performed by local laboratory and per local guidelines) 3.Known complete or partial dipyrimidine dehydrogenase (DPD) enzyme deficiency (testing for DPD enzyme deficiency is not mandatory unless required by local regulations and can be conducted at a local laboratory) 4.For participants treated with irinotecan: Known history or clinical evidence of reduced UGT1A1 activity (testing for UGT1A1 status is not mandatory unless required by local regulations and can be conducted at a local laboratory) 5.Presence of symptomatic CNS metastases, or CNS metastases that requires directed therapy (such as focal radiotherapy or surgery), or increasing doses of corticosteroids 2 weeks prior to study entry. Participants with treated symptomatic brain metastases should be neurologically stable for 4 weeks post-treatment & prior to study entry & at a dose of = 10 mg per day prednisone or equivalent for at least 2 weeks before administration of any study treatment. 6.Known history of severe allergy or hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes (monoclonal antibodies) or contraindication to any of the study drugs as outlined in the 'Contraindications' or 'Warnings and Precautions' sections of the SOC local prescribing information 7.Participant is currently receiving other anti-cancer therapy or received other investigational product within 30 days or 5 half-lives prior to initiation of study treatment whichever is longer 8.Participant is currently receiving any of the prohibited medications as outlined in the protocol or in the SOC anti-cancer therapy local prescribing information & these cannot be discontinued = 7 days or 5 half-lives whichever is longer before the first dose of drug 9.Participant has not recovered from a major surgery performed prior to start of study treatment or has had a major surgery within 4 weeks days prior to start of study treatment 10.Radiation therapy = 4 weeks or brain-radiotherapy = 4 weeks prior to start of study treatment 11.Impaired cardiac function or clinically significant cardio-vascular disease such as: •Congestive heart failure requiring treatment (NYHA grade =2), or clinically significant arrhythmia (including uncontrolled atrial flutter/fibrillation) •Acute myocardial infarction, unstable angina pectoris, coronary stenting, or bypass surgery 2 x ULN •Cardiac valvulopathy= grade 2 •Uncontrolled hypertension defined by a systolic blood pressure =160 mg &/or diastolic blood pressure =100 mg Hg •Medical history or current diagnosis of myocarditis 12.History of positive test for human immunodeficiency virus (HIV) 13.Active or chronic hepatitis B virus (HBV) or hepatitis C virus 14.Active untreated or uncontrolled systemic fungal, bacterial or viral infection (incl. COVID-19) which in the opinion of the investigator places the study participant at unacceptable risk 15.Use of hematopoietic growth factors or transfusion support = 2 weeks prior to start of study treatment 16.Participant has conditions that are considered to have a high risk of clinically significant gastrointestinal tract bleeding or any other condition associated or history of significant bleeding 17.Serious
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Safety run-in: To confirm the recommended phase 2 dose (RP2D) of each investigational arm (NIS793 or or NIS793 plus tislelizumab or any investigational drug(s) in combination with SOC) (SOC: either modified FOLFOX6 + bevacizumab or FOLFIRI+ bevacizumab chemotherapy regimen) Expansion part: To evaluate preliminary efficacy of each investigational arm (NIS793 or or NIS793 plus tislelizumab or any investigational drug(s) in combination with SOC anti-cancer therapy) versus control arm(SOC anti-cancer therapy) in terms of progression-free survival (PFS) by Investigator's assessment per RECIST 1.1 ;Secondary Objective: Safety run-in: 1. To characterize the safety and tolerability of each investigational arm (NIS793 or NIS793+tislelizumab or any investigational drug(s) in combination with SOC) 2. Preliminary anti-tumor activity of each investigational arm 3. To characterize the pharmacokinetics (PK) of each investigational treatment (NIS793 or NIS793+tislelizumab in combination with SOC) 4. To characterize the immunogenicity of each investigational treatment Expansion part: 1. To evaluate and compare efficacy of each investigational arm and control arm in terms of ORR, DCR, DOR, TTR by Investigator's assessment per RECIST 1.1 2. To evaluate and compare the overall survival (OS) of each investigational arm and control arm 3. Safety and tolerability 4. To characterize the PK of each investigational treatment (NIS793 or NIS793+tislelizumab in combination with SOC) 5. To characterize the immunogenicity of components of each investigational arm, control arm;Primary end point(s): Safety run-in: Incidence of DLTs during the first treatment cycle (4 weeks) of treatment Expansion part: Progression-free survival (PFS) by Investigator’s assessment per RECIST 1.1;Timepoint(s) of evaluation of this end point: safety run-in: 4 weeks of treatment expansion part: until progression of the disease | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety run-in: 1. Safety: Incidence and severity of AEs including changes in laboratory parameters, vital signs and ECG parameters 2. Tolerability: Dose interruptions, reductions and dose intensity 3. PFS, overall response rate (ORR), disease control rate (DCR), duration of response (DOR) and time to response (TTR)by Investigator's assessment per RECIST 1.1 and Overall survival (OS) 4. Drug concentrations in serum or plasma of each investigational treatment and components of SOC therapy (bevacizumab, irinotecan, SN-38) over time and derived PK parameters (e.g. Ctrough, Cmax) 5. Incidence of antidrug antibodies (ADA), prevalence at baseline and ADA incidence during the treatment for investigational treatment(s) and bevacizumab. expansion part: 1. ORR, DCR, DOR, TTR by investigator's assessment by RECIST 1.1 2. OS 3. Incidence and severity of AEs, changes in laboratory parameters, vital signs and ECG parameters; dose interruptions, reductions and dose intensity 4. Drug concentrations in serum or plasma of each investigational treatment and components of SOC therapy (bevacizumab, irinotecan, SN-38) over time and derived PK parameters (e.g. Ctrough, Cmax) 5. Incidence of antidrug antibodies (ADA), prevalence at baseline and ADA incidence during the treatment for investigational treatment(s) and bevacizumab.;Timepoint(s) of evaluation of this end point: safety run-in: 1,2 - 4 weeks of treatment 3 - end of treatment 4,5 - at protocol defined timepoints expansion part: 1, 2, 3 - at the end of treatment 4,5 - at protocol defined timepoints | — |
Countries
Australia, Belgium, Canada, Czechia, Czech Republic, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Singapore, Spain, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactInformacní služba – klin. hodnocení
Novartis s.r.o.
Outcome results
None listed