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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04952753




Registration number
NCT04952753
Ethics application status
Date submitted
28/06/2021
Date registered
7/07/2021

Titles & IDs
Public title
Study of NIS793 and Other Novel Investigational Combinations With SOC Anti-cancer Therapy for the 2L Treatment of mCRC
Scientific title
An Open-label, Multi-center, ph II Platform Study Evaluating the Efficacy and Safety of NIS793 and Other New Investigational Drug Combinations With SOC Anti-cancer Therapy for the 2L Treatment of Metastatic Colorectal Cancer (mCRC)
Secondary ID [1] 0 0
2021-000553-40
Secondary ID [2] 0 0
CNIS793E12201
Universal Trial Number (UTN)
Trial acronym
daNIS-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - NIS793
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Modified FOLFOX6
Treatment: Drugs - FOLFIRI
Treatment: Drugs - Tislelizumab

Experimental: Safety run-in: NIS793+SOC (Investigational arm 1) - In the safety run-in part for investigational arm 1, participants will be treated with a combination of SOC anti-cancer therapy (bevacizumab with either modified FOLFOX6 or FOLFIRI) and NIS793 to confirm the RP2D of the NIS793

Experimental: Expansion: NIS793+SOC (Investigational arm 1) - In the expansion part, participants in the investigational arm 1 will be treated with a combination of SOC anti-cancer therapy (bevacizumab with either modified FOLFOX6 or FOLFIRI) and NIS793 at the RP2D defined in the safety run-in

Active comparator: Expansion: SOC (control arm) - In the expansion part, participants in the control arm will be treated with a combination of SOC anti-cancer therapy (bevacizumab with either modified FOLFOX6 or FOLFIRI)

Experimental: Safety run-in: NIS793+Tislelizumab+SOC (Investigational arm 2) - In the safety run-in part for investigational arm 2, participants will be treated with a combination of SOC anti-cancer therapy (bevacizumab with either modified FOLFOX6 or FOLFIRI), NIS793 and tislelizumab to confirm the RP2D of NIS793.

Experimental: Expansion: NIS793+Tislelizumab+SOC (Investigational arm 2) - In the expansion part, participants in the investigational arm 2 will be treated with a combination of SOC anti-cancer therapy (bevacizumab with either modified FLOFOX6 or FOLFIRI) with NIS793 and tislelizumab at the RP2D for NIS793 defined in the safety run-in


Treatment: Drugs: NIS793
Investigational drug NIS793 will be administered intravenously (IV) at the dose and schedule determined in the safety run-in part.

Treatment: Drugs: Bevacizumab
Bevacizumab will be administered IV

Treatment: Drugs: Modified FOLFOX6
5-fluorouracil \[continuous infusion\], leucovorin \[administered IV\] (or levoleucovorin \[administered IV\]), and oxaliplatin \[administered IV\]

Treatment: Drugs: FOLFIRI
5-fluorouracil \[continuous infusion\], leucovorin \[administered IV\] (or levoleucovorin \[administered IV\]), and irinotecan \[administered IV\]

Treatment: Drugs: Tislelizumab
Investigational drug tislelizumab will be administered intravenously (IV).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety run-in: Percentage of participants with dose limiting toxicities (DLTs) during the first cycle (4 weeks) of treatment.
Timepoint [1] 0 0
Up to 4 weeks
Primary outcome [2] 0 0
Expansion: Progression-free survival (PFS) by investigator assessment per RECIST 1.1
Timepoint [2] 0 0
From randomization up to disease progression or death, assessed up to approximately 12 months
Secondary outcome [1] 0 0
Safety run-in: Percentage of participants with Adverse Events (AEs)
Timepoint [1] 0 0
Up to approximately 12 months
Secondary outcome [2] 0 0
Safety run-in: Percentage of participants with dose interruptions and dose reductions of investigational drug
Timepoint [2] 0 0
Upto approximately 12 months
Secondary outcome [3] 0 0
Safety run-in: Dose intensity of investigational drug
Timepoint [3] 0 0
Up to approximately 12 months
Secondary outcome [4] 0 0
Safety run-in: PFS by investigator assessment per RECIST 1.1
Timepoint [4] 0 0
From enrollment up to disease progression or death, assessed up to approximately 12 months
Secondary outcome [5] 0 0
Safety run-in: Overall response rate (ORR) by investigator assessment per RECIST 1.1
Timepoint [5] 0 0
Up to approximately 12 months
Secondary outcome [6] 0 0
Safety run-in: Disease control rate (DCR) by investigator assessment per RECIST 1.1
Timepoint [6] 0 0
Up to approximately 12 months
Secondary outcome [7] 0 0
Safety run-in: Duration of response (DOR) by investigator assessment per RECIST 1.1
Timepoint [7] 0 0
From first documented response up to disease progression or death, assessed up to approximately 12 months
Secondary outcome [8] 0 0
Safety run-in part: Overall Survival (OS)
Timepoint [8] 0 0
From enrollment up to death, assessed up to approximately 12 months
Secondary outcome [9] 0 0
Safety run-in: Time to response (TTR) by investigator assessment per RECIST 1.1
Timepoint [9] 0 0
From enrollment up to first documented response, assessed up to approximately 12 months
Secondary outcome [10] 0 0
Expansion: Percentage of participants with Adverse Events (AEs)
Timepoint [10] 0 0
Up to approximately 12 months
Secondary outcome [11] 0 0
Expansion part: Percentage of participants with dose interruptions and dose reductions of investigational drug
Timepoint [11] 0 0
Up to approximately 12 months
Secondary outcome [12] 0 0
Expansion: Dose intensity of investigational drug
Timepoint [12] 0 0
Up to approximately 12 months
Secondary outcome [13] 0 0
Expansion: Overall response rate (ORR) by investigator assessment per RECIST 1.1
Timepoint [13] 0 0
Up to approximately 12 months
Secondary outcome [14] 0 0
Expansion: Disease control rate (DCR) by investigator assessment per RECIST 1.1
Timepoint [14] 0 0
Up to approximately 12 months
Secondary outcome [15] 0 0
Expansion: Duration of response (DOR) by investigator assessment per RECIST 1.1
Timepoint [15] 0 0
From first documented response up to disease progression or death, assessed up to approximately 12 months
Secondary outcome [16] 0 0
Expansion part: Overall Survival (OS)
Timepoint [16] 0 0
From randomization up to death, assessed up to approximately 12 months
Secondary outcome [17] 0 0
Expansion: Time to response (TTR) by investigator assessment per RECIST 1.1
Timepoint [17] 0 0
From enrollment up to first documented response, assessed up to approximately 12 months
Secondary outcome [18] 0 0
Maximum concentration (Cmax) of NIS793
Timepoint [18] 0 0
From the date of first study drug intake up to approximately 12 months
Secondary outcome [19] 0 0
Maximum concentration (Cmax) of tislelizumab
Timepoint [19] 0 0
From the date of first study drug intake up to approximately 12 months
Secondary outcome [20] 0 0
Trough Concentration (Ctrough) of NIS793
Timepoint [20] 0 0
From the date of first study drug intake up to approximately 12 months
Secondary outcome [21] 0 0
Trough Concentration (Ctrough) tislelizumab
Timepoint [21] 0 0
From the date of first study drug intake up to approximately 12 months
Secondary outcome [22] 0 0
Antidrug antibodies (ADA) at baseline
Timepoint [22] 0 0
Baseline
Secondary outcome [23] 0 0
ADA incidence on treatment
Timepoint [23] 0 0
From the date of first study drug intake up to approximately 12 months

Eligibility
Key inclusion criteria
Key

* Participants age 18 or older with 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.
* Presence of at least one measurable lesion assessed by CT and/or MRI according to RECIST 1.1.
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
* Adequate organ function (assessed by central laboratory for eligibility).

Key
Minimum age
18 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Previously administered TGF-ß targeted therapies or anti-cancer immunotherapy.
* Microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) and/or BRAFV600 mutation positive colorectal cancer.
* 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).
* 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).
* Participants who have not recovered from a major surgery performed prior to start of study treatment or have had a major surgery within 4 weeks prior to start of study treatment.
* Impaired cardiac function or clinically significant cardio-vascular disease.
* Participants with 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.
* Stroke or transient ischemic attack, or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 3 months before start of study treatment.
* 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 required.

Other inclusion/exclusion criteria may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/11/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
6/01/2025
Actual
Sample size
Target
Accrual to date
Final
204
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Adelaide
Recruitment hospital [2] 0 0
Novartis Investigative Site - Bendigo
Recruitment hospital [3] 0 0
Novartis Investigative Site - Perth
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3550 - Bendigo
Recruitment postcode(s) [3] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
New Jersey
Country [5] 0 0
United States of America
State/province [5] 0 0
Tennessee
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
Belgium
State/province [7] 0 0
Bruxelles
Country [8] 0 0
Belgium
State/province [8] 0 0
Leuven
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
Canada
State/province [10] 0 0
Quebec
Country [11] 0 0
Czechia
State/province [11] 0 0
Czech Republic
Country [12] 0 0
Czechia
State/province [12] 0 0
CZE
Country [13] 0 0
Czechia
State/province [13] 0 0
Praha 4
Country [14] 0 0
France
State/province [14] 0 0
Avignon
Country [15] 0 0
France
State/province [15] 0 0
Creteil
Country [16] 0 0
France
State/province [16] 0 0
Nantes Cedex 1
Country [17] 0 0
Germany
State/province [17] 0 0
Berlin
Country [18] 0 0
Germany
State/province [18] 0 0
Bochum
Country [19] 0 0
Germany
State/province [19] 0 0
Dresden
Country [20] 0 0
Germany
State/province [20] 0 0
Essen
Country [21] 0 0
Germany
State/province [21] 0 0
Frankfurt
Country [22] 0 0
Germany
State/province [22] 0 0
Hamburg
Country [23] 0 0
Germany
State/province [23] 0 0
Ulm
Country [24] 0 0
Hong Kong
State/province [24] 0 0
Pokfulam
Country [25] 0 0
Hong Kong
State/province [25] 0 0
Shatin
Country [26] 0 0
Israel
State/province [26] 0 0
Haifa
Country [27] 0 0
Israel
State/province [27] 0 0
Petach Tikva
Country [28] 0 0
Italy
State/province [28] 0 0
MI
Country [29] 0 0
Italy
State/province [29] 0 0
RM
Country [30] 0 0
Japan
State/province [30] 0 0
Aichi
Country [31] 0 0
Japan
State/province [31] 0 0
Chiba
Country [32] 0 0
Japan
State/province [32] 0 0
Kanagawa
Country [33] 0 0
Japan
State/province [33] 0 0
Osaka
Country [34] 0 0
Japan
State/province [34] 0 0
Toyama
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Seoul
Country [36] 0 0
Singapore
State/province [36] 0 0
Singapore
Country [37] 0 0
Spain
State/province [37] 0 0
Barcelona
Country [38] 0 0
Spain
State/province [38] 0 0
Cantabria
Country [39] 0 0
Spain
State/province [39] 0 0
Catalunya
Country [40] 0 0
Spain
State/province [40] 0 0
Madrid
Country [41] 0 0
Switzerland
State/province [41] 0 0
St Gallen
Country [42] 0 0
Taiwan
State/province [42] 0 0
Tainan
Country [43] 0 0
Taiwan
State/province [43] 0 0
Taipei
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Grampian Region
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Cambridge
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04952753