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Study of NIS793 and Other Novel Investigational Combinations With SOC Anti-cancer Therapy for the 2L Treatment of mCRC (daNIS-3)

Primary Purpose

Metastatic Colorectal Cancer

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
NIS793
Bevacizumab
Modified FOLFOX6
FOLFIRI
Tislelizumab
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring NIS793, metastatic colorectal cancer, colorectal cancer, transforming growth factor βeta (TGF-β), anti PD-1 monoclonal antibody

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • 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 Exclusion Criteria:

  • Previously administered TGF-β 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

Sites / Locations

  • The Angeles Clinic and Research Institute .
  • University of Michigan Medical Center .
  • Washington University School .
  • Astera Cancer Center
  • Sarah Cannon Research Institute DeptofSarahCannonRes.Inst. (2)
  • Uni of TX MD Anderson Cancer Cntr
  • Mays Cancer Center
  • Novartis Investigative Site
  • Novartis Investigative Site
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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Active Comparator

Experimental

Experimental

Arm Label

Safety run-in: NIS793+SOC (Investigational arm 1)

Expansion: NIS793+SOC (Investigational arm 1)

Expansion: SOC (control arm)

Safety run-in: NIS793+Tislelizumab+SOC (Investigational arm 2)

Expansion: NIS793+Tislelizumab+SOC (Investigational arm 2)

Arm Description

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

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

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)

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.

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

Outcomes

Primary Outcome Measures

Safety run-in: Percentage of participants with dose limiting toxicities (DLTs) during the first cycle (4 weeks) of treatment.
Percentage of participants with DLTs during the first cycle of treatment. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness or concomitant medication that occurs within the first cycle of treatment with NIS793 with or without tislelizumab in combination with Bevacizumab and modified FOLFOX6/ FOLFIRI and meets protocol defined DLT criteria.
Expansion: Progression-free survival (PFS) by investigator assessment per RECIST 1.1
PFS defined as the time from the date of enrollment (run-in part) or randomization (randomized part) to the date of the first documented progression based on investigator assessment and according to RECIST 1.1 or death due to any cause.

Secondary Outcome Measures

Safety run-in: Percentage of participants with Adverse Events (AEs)
Percentage of participants with AEs and SAEs including changes in laboratory parameters, vital signs, body weight and cardiac assessments
Safety run-in: Percentage of participants with dose interruptions and dose reductions of investigational drug
Tolerability measured by the percentage of subjects who have dose adjustments (interruptions or reductions) of investigational drug (e.g. NIS793, NIS793+tislelizumab)
Safety run-in: Dose intensity of investigational drug
Tolerability measured by the dose intensity of investigational drug (e.g. NIS793, NIS793+tislelizumab). Dose intensity will be computed as the ratio of actual cumulative dose received and actual duration of exposure
Safety run-in: PFS by investigator assessment per RECIST 1.1
PFS defined as the time from the date of enrollment to the date of the first documented progression based on investigator assessment and according to RECIST 1.1 or death due to any cause.
Safety run-in: Overall response rate (ORR) by investigator assessment per RECIST 1.1
ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR), as per investigator assessment and according to RECIST 1.1
Safety run-in: Disease control rate (DCR) by investigator assessment per RECIST 1.1
DCR is the proportion of participants with BOR of CR or PR or stable disease (SD) as per investigator assessment and according to RECIST 1.1
Safety run-in: Duration of response (DOR) by investigator assessment per RECIST 1.1
DOR is defined as the duration of time between the date of the first documented response (CR or PR) and the date of first documented progression or death due to any cause
Safety run-in part: Overall Survival (OS)
OS is defined as the time from the date of enrollment to date of death due to any cause.
Safety run-in: Time to response (TTR) by investigator assessment per RECIST 1.1
TTR is defined as the duration of time between the date of enrollment and the date of first documented response of either CR or PR.
Expansion: Percentage of participants with Adverse Events (AEs)
Percentage of participants with AEs and SAEs including changes in laboratory parameters, vital signs, body weight and cardiac assessments
Expansion part: Percentage of participants with dose interruptions and dose reductions of investigational drug
Tolerability measured by the percentage of subjects who have dose adjustments (interruptions) of investigational drug (e.g. NIS793, NIS793+tislelizumab)
Expansion: Dose intensity of investigational drug
Tolerability measured by the dose intensity of investigational drug (e.g. NIS793, NIS793+Tislelizumab). Dose intensity will be computed as the ratio of actual cumulative dose received and actual duration of exposure
Expansion: Overall response rate (ORR) by investigator assessment per RECIST 1.1
ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR), as per investigator assessment and according to RECIST 1.1
Expansion: Disease control rate (DCR) by investigator assessment per RECIST 1.1
DCR is the proportion of participants with BOR of CR or PR or stable disease (SD) as per investigator assessment and according to RECIST 1.1
Expansion part: Overall Survival (OS)
OS is defined as the time from the date of enrollment to date of death due to any cause.
Expansion: Time to response (TTR) by investigator assessment per RECIST 1.1
TTR is defined as the duration of time between the date of enrollment and the date of first documented response of either CR or PR.
Maximum concentration (Cmax) of NIS793
Blood samples will be collected at indicated time-points for analysis of Cmax of NIS793
Maximum concentration (Cmax) of tislelizumab
Blood samples will be collected at indicated time-points for analysis of Cmax of tislelizumab
Maximum concentration (Cmax) of bevacizumab
Blood samples will be collected at indicated time-points for analysis of Cmax of bevacizumab
Maximum concentration (Cmax) of irinotecan and its metabolite (SN38)
Blood samples will be collected at indicated time-points for analysis of Cmax of irinotecan and SN-38
Trough Concentration (Ctrough) of NIS793
Blood samples will be collected at indicated time-points for analysis of Ctrough of NIS793
Trough Concentration (Ctrough) tislelizumab
Blood samples will be collected at indicated time-points for analysis of Ctrough of tislelizumab
Trough Concentration (Ctrough) of bevacizumab
Blood samples will be collected at indicated time-points for analysis of Ctrough of bevacizumab
Trough Concentration (Ctrough) of irinotecan and its metabolite (SN38)
Blood samples will be collected at indicated time-points for analysis of Ctrough of irinotecan and SN-38
Antidrug antibodies (ADA) at baseline
Prevalence of ADA (anti-NIS793, anti-bevacizumab, anti-tislelizumab) at baseline is defined as the proportion of participants who have an ADA positive result at baseline
ADA incidence on treatment
Incidence of ADA (anti-NIS793, anti-bevacizumab, anti-tislelizumab) on treatment is defined as the proportion of participants who are treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)

Full Information

First Posted
June 28, 2021
Last Updated
October 9, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT04952753
Brief Title
Study of NIS793 and Other Novel Investigational Combinations With SOC Anti-cancer Therapy for the 2L Treatment of mCRC
Acronym
daNIS-3
Official 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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 15, 2021 (Actual)
Primary Completion Date
May 20, 2024 (Anticipated)
Study Completion Date
September 20, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to evaluate the preliminary efficacy and safety of NIS793 and other novel investigational combinations with standard of care (SOC) anti-cancer therapy vs SOC anti-cancer therapy for the second line treatment of mCRC. This study aims to explore whether different mechanisms of action may reverse resistance and improve responsiveness to the currently considered SOC anti-cancer therapy in the second line metastatic colorectal cancer (mCRC) setting.
Detailed Description
This is an open-label, multi-center, phase II, 2-part platform study with Safety run-in and Expansion parts. The platform design of this study is adaptive to allow flexibility in the introduction of additional treatment arms with new investigational drugs in combination with SOC anti-cancer therapy for the second line treatment of mCRC. The study will include a control arm that will enroll participants treated with SOC anti-cancer therapy (bevacizumab with mFOLFOX6 or FOLFIRI) for the second line treatment of mCRC. The choice of the chemotherapy medications (mFOLFOX6 or FOLFIRI) will be determined by the Investigator based on prior exposure to oxaliplatin or irinotecan. Each investigational arm will include a combination of an investigational drug and the SOC anti-cancer therapy. The first investigational arm of the study will explore the combination of anti-transforming growth factor β (TGF-β) monoclonal antibody, NIS793 with SOC anti-cancer therapy. The second investigational arm of the study will explore the combination of anti-transforming growth factor β (TGF-β) monoclonal antibody, NIS793 with Tislelizumab, which is an anti-PD1 monoclonal antibody, and SOC anti-cancer therapy. Combination of other investigational drugs with SOC anti-cancer therapy may be added by protocol amendments an additional investigational arms. In each investigational arm, a Safety run-in part will be conducted before opening the expansion part to confirm the recommended phase 2 dose (RP2D) for a combination of any investigational drug with SOC anti-cancer therapy unless the dose has been confirmed externally to this trial. The decision to open the Expansion part of the study will be based on dose confirmation of investigational drug with available safety, relevant PK and other relevant data from Safety run-in part. Participants in the expansion part will be randomized in 1:2 ratio to the control arm or investigational arm.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
NIS793, metastatic colorectal cancer, colorectal cancer, transforming growth factor βeta (TGF-β), anti PD-1 monoclonal antibody

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
205 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Safety run-in: NIS793+SOC (Investigational arm 1)
Arm Type
Experimental
Arm Description
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
Arm Title
Expansion: NIS793+SOC (Investigational arm 1)
Arm Type
Experimental
Arm Description
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
Arm Title
Expansion: SOC (control arm)
Arm Type
Active Comparator
Arm Description
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)
Arm Title
Safety run-in: NIS793+Tislelizumab+SOC (Investigational arm 2)
Arm Type
Experimental
Arm Description
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.
Arm Title
Expansion: NIS793+Tislelizumab+SOC (Investigational arm 2)
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
NIS793
Intervention Description
Investigational drug NIS793 will be administered intravenously (IV) at the dose and schedule determined in the safety run-in part.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Intervention Description
Bevacizumab will be administered IV
Intervention Type
Drug
Intervention Name(s)
Modified FOLFOX6
Other Intervention Name(s)
5FU+Leucovorin+Oxaliplatin
Intervention Description
5-fluorouracil [continuous infusion], leucovorin [administered IV] (or levoleucovorin [administered IV]), and oxaliplatin [administered IV]
Intervention Type
Drug
Intervention Name(s)
FOLFIRI
Other Intervention Name(s)
5FU+Leucovorin+Irinotecan
Intervention Description
5-fluorouracil [continuous infusion], leucovorin [administered IV] (or levoleucovorin [administered IV]), and irinotecan [administered IV]
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Other Intervention Name(s)
VDT482
Intervention Description
Investigational drug tislelizumab will be administered intravenously (IV).
Primary Outcome Measure Information:
Title
Safety run-in: Percentage of participants with dose limiting toxicities (DLTs) during the first cycle (4 weeks) of treatment.
Description
Percentage of participants with DLTs during the first cycle of treatment. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness or concomitant medication that occurs within the first cycle of treatment with NIS793 with or without tislelizumab in combination with Bevacizumab and modified FOLFOX6/ FOLFIRI and meets protocol defined DLT criteria.
Time Frame
Up to 4 weeks
Title
Expansion: Progression-free survival (PFS) by investigator assessment per RECIST 1.1
Description
PFS defined as the time from the date of enrollment (run-in part) or randomization (randomized part) to the date of the first documented progression based on investigator assessment and according to RECIST 1.1 or death due to any cause.
Time Frame
From randomization up to disease progression or death, assessed up to approximately 12 months
Secondary Outcome Measure Information:
Title
Safety run-in: Percentage of participants with Adverse Events (AEs)
Description
Percentage of participants with AEs and SAEs including changes in laboratory parameters, vital signs, body weight and cardiac assessments
Time Frame
Up to approximately 12 months
Title
Safety run-in: Percentage of participants with dose interruptions and dose reductions of investigational drug
Description
Tolerability measured by the percentage of subjects who have dose adjustments (interruptions or reductions) of investigational drug (e.g. NIS793, NIS793+tislelizumab)
Time Frame
Upto approximately 12 months
Title
Safety run-in: Dose intensity of investigational drug
Description
Tolerability measured by the dose intensity of investigational drug (e.g. NIS793, NIS793+tislelizumab). Dose intensity will be computed as the ratio of actual cumulative dose received and actual duration of exposure
Time Frame
Up to approximately 12 months
Title
Safety run-in: PFS by investigator assessment per RECIST 1.1
Description
PFS defined as the time from the date of enrollment to the date of the first documented progression based on investigator assessment and according to RECIST 1.1 or death due to any cause.
Time Frame
From enrollment up to disease progression or death, assessed up to approximately 12 months
Title
Safety run-in: Overall response rate (ORR) by investigator assessment per RECIST 1.1
Description
ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR), as per investigator assessment and according to RECIST 1.1
Time Frame
Up to approximately 12 months
Title
Safety run-in: Disease control rate (DCR) by investigator assessment per RECIST 1.1
Description
DCR is the proportion of participants with BOR of CR or PR or stable disease (SD) as per investigator assessment and according to RECIST 1.1
Time Frame
Up to approximately 12 months
Title
Safety run-in: Duration of response (DOR) by investigator assessment per RECIST 1.1
Description
DOR is defined as the duration of time between the date of the first documented response (CR or PR) and the date of first documented progression or death due to any cause
Time Frame
From first documented response up to disease progression or death, assessed up to approximately 12 months
Title
Safety run-in part: Overall Survival (OS)
Description
OS is defined as the time from the date of enrollment to date of death due to any cause.
Time Frame
From enrollment up to death, assessed up to approximately 12 months
Title
Safety run-in: Time to response (TTR) by investigator assessment per RECIST 1.1
Description
TTR is defined as the duration of time between the date of enrollment and the date of first documented response of either CR or PR.
Time Frame
From enrollment up to first documented response, assessed up to approximately 12 months
Title
Expansion: Percentage of participants with Adverse Events (AEs)
Description
Percentage of participants with AEs and SAEs including changes in laboratory parameters, vital signs, body weight and cardiac assessments
Time Frame
Up to approximately 12 months
Title
Expansion part: Percentage of participants with dose interruptions and dose reductions of investigational drug
Description
Tolerability measured by the percentage of subjects who have dose adjustments (interruptions) of investigational drug (e.g. NIS793, NIS793+tislelizumab)
Time Frame
Up to approximately 12 months
Title
Expansion: Dose intensity of investigational drug
Description
Tolerability measured by the dose intensity of investigational drug (e.g. NIS793, NIS793+Tislelizumab). Dose intensity will be computed as the ratio of actual cumulative dose received and actual duration of exposure
Time Frame
Up to approximately 12 months
Title
Expansion: Overall response rate (ORR) by investigator assessment per RECIST 1.1
Description
ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR), as per investigator assessment and according to RECIST 1.1
Time Frame
Up to approximately 12 months
Title
Expansion: Disease control rate (DCR) by investigator assessment per RECIST 1.1
Description
DCR is the proportion of participants with BOR of CR or PR or stable disease (SD) as per investigator assessment and according to RECIST 1.1
Time Frame
Up to approximately 12 months
Title
Expansion part: Overall Survival (OS)
Description
OS is defined as the time from the date of enrollment to date of death due to any cause.
Time Frame
From randomization up to death, assessed up to approximately 12 months
Title
Expansion: Time to response (TTR) by investigator assessment per RECIST 1.1
Description
TTR is defined as the duration of time between the date of enrollment and the date of first documented response of either CR or PR.
Time Frame
From enrollment up to first documented response, assessed up to approximately 12 months
Title
Maximum concentration (Cmax) of NIS793
Description
Blood samples will be collected at indicated time-points for analysis of Cmax of NIS793
Time Frame
From the date of first study drug intake up to approximately 12 months
Title
Maximum concentration (Cmax) of tislelizumab
Description
Blood samples will be collected at indicated time-points for analysis of Cmax of tislelizumab
Time Frame
From the date of first study drug intake up to approximately 12 months
Title
Maximum concentration (Cmax) of bevacizumab
Description
Blood samples will be collected at indicated time-points for analysis of Cmax of bevacizumab
Time Frame
From the date of first study drug intake up to approximately 12 months
Title
Maximum concentration (Cmax) of irinotecan and its metabolite (SN38)
Description
Blood samples will be collected at indicated time-points for analysis of Cmax of irinotecan and SN-38
Time Frame
From the date of first study drug intake up to approximately 12 months
Title
Trough Concentration (Ctrough) of NIS793
Description
Blood samples will be collected at indicated time-points for analysis of Ctrough of NIS793
Time Frame
From the date of first study drug intake up to approximately 12 months
Title
Trough Concentration (Ctrough) tislelizumab
Description
Blood samples will be collected at indicated time-points for analysis of Ctrough of tislelizumab
Time Frame
From the date of first study drug intake up to approximately 12 months
Title
Trough Concentration (Ctrough) of bevacizumab
Description
Blood samples will be collected at indicated time-points for analysis of Ctrough of bevacizumab
Time Frame
From the date of first study intake up to approximately 12 months.
Title
Trough Concentration (Ctrough) of irinotecan and its metabolite (SN38)
Description
Blood samples will be collected at indicated time-points for analysis of Ctrough of irinotecan and SN-38
Time Frame
From the date of first study drug intake up to approximately 12 months.
Title
Antidrug antibodies (ADA) at baseline
Description
Prevalence of ADA (anti-NIS793, anti-bevacizumab, anti-tislelizumab) at baseline is defined as the proportion of participants who have an ADA positive result at baseline
Time Frame
Baseline
Title
ADA incidence on treatment
Description
Incidence of ADA (anti-NIS793, anti-bevacizumab, anti-tislelizumab) on treatment is defined as the proportion of participants who are treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)
Time Frame
From the date of first study drug intake up to approximately 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: 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 Exclusion Criteria: Previously administered TGF-β 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
The Angeles Clinic and Research Institute .
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
Facility Name
University of Michigan Medical Center .
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0331
Country
United States
Facility Name
Washington University School .
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Astera Cancer Center
City
East Brunswick
State/Province
New Jersey
ZIP/Postal Code
08816
Country
United States
Facility Name
Sarah Cannon Research Institute DeptofSarahCannonRes.Inst. (2)
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Uni of TX MD Anderson Cancer Cntr
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Mays Cancer Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Novartis Investigative Site
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Novartis Investigative Site
City
Bendigo
State/Province
Victoria
ZIP/Postal Code
3550
Country
Australia
Facility Name
Novartis Investigative Site
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Novartis Investigative Site
City
Bruxelles
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Novartis Investigative Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Brampton
State/Province
Ontario
ZIP/Postal Code
L6R 3J7
Country
Canada
Facility Name
Novartis Investigative Site
City
Cambridge
State/Province
Ontario
ZIP/Postal Code
N1R 3G2
Country
Canada
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W 1T8
Country
Canada
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
Novartis Investigative Site
City
Brno
State/Province
Czech Republic
ZIP/Postal Code
656 53
Country
Czechia
Facility Name
Novartis Investigative Site
City
Hradec Kralove
State/Province
CZE
ZIP/Postal Code
500 05
Country
Czechia
Facility Name
Novartis Investigative Site
City
Praha 4
ZIP/Postal Code
140 59
Country
Czechia
Facility Name
Novartis Investigative Site
City
Avignon
ZIP/Postal Code
84082
Country
France
Facility Name
Novartis Investigative Site
City
Creteil
ZIP/Postal Code
94010
Country
France
Facility Name
Novartis Investigative Site
City
Nantes Cedex 1
ZIP/Postal Code
44093
Country
France
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Novartis Investigative Site
City
Bochum
ZIP/Postal Code
44791
Country
Germany
Facility Name
Novartis Investigative Site
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Frankfurt
ZIP/Postal Code
60488
Country
Germany
Facility Name
Novartis Investigative Site
City
Hamburg
ZIP/Postal Code
20249
Country
Germany
Facility Name
Novartis Investigative Site
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Novartis Investigative Site
City
Pokfulam
Country
Hong Kong
Facility Name
Novartis Investigative Site
City
Shatin New Territories
Country
Hong Kong
Facility Name
Novartis Investigative Site
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Novartis Investigative Site
City
Petach Tikva
ZIP/Postal Code
4941492
Country
Israel
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20133
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20162
Country
Italy
Facility Name
Novartis Investigative Site
City
Rozzano
State/Province
MI
ZIP/Postal Code
20089
Country
Italy
Facility Name
Novartis Investigative Site
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
464 8681
Country
Japan
Facility Name
Novartis Investigative Site
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
277 8577
Country
Japan
Facility Name
Novartis Investigative Site
City
Kawasaki-city
State/Province
Kanagawa
ZIP/Postal Code
216-8511
Country
Japan
Facility Name
Novartis Investigative Site
City
Osaka-city
State/Province
Osaka
ZIP/Postal Code
541-8567
Country
Japan
Facility Name
Novartis Investigative Site
City
Toyama-city
State/Province
Toyama
ZIP/Postal Code
930-0194
Country
Japan
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
119074
Country
Singapore
Facility Name
Novartis Investigative Site
City
Sabadell
State/Province
Barcelona
ZIP/Postal Code
08208
Country
Spain
Facility Name
Novartis Investigative Site
City
Santander
State/Province
Cantabria
ZIP/Postal Code
39008
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08036
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Novartis Investigative Site
City
St. Gallen
ZIP/Postal Code
9007
Country
Switzerland
Facility Name
Novartis Investigative Site
City
Tainan
ZIP/Postal Code
70403
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Aberdeen
State/Province
Scotland
ZIP/Postal Code
AB25 2ZN
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Cambridge
ZIP/Postal Code
01223 7620
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Oxford
ZIP/Postal Code
OX3 7LJ
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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

Learn more about this trial

Study of NIS793 and Other Novel Investigational Combinations With SOC Anti-cancer Therapy for the 2L Treatment of mCRC

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