Metastatic Colorectal CancerPhase 2daNIS-3NCT04952753
Study of NIS793 and Other Novel Investigational Combinations With SOC Anti-cancer Therapy for the 2L Treatment of mCRC
A Phase 2 study testing NIS793, Bevacizumab and Modified FOLFOX6 in people with Metastatic Colorectal Cancer, run by Novartis Pharmaceuticals at 55 sites in 17 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- NIS793, Bevacizumab and Modified FOLFOX6
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 204 participants
- Where
- 55 sitesin 17 countries
- Study dates
- 15 Nov 2021to 20 Jan 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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
Trial locations and contacts
55 sites in 17 countries.
55 sites in 17 countries
United States7 sites
University of Michigan Medical
Ann Arbor, Michigan, 48109-0331
Astera Cancer Center
East Brunswick, New Jersey, 08816
Uni Of TX MD Anderson Cancer Cntr
Houston, Texas, 77030
The Angeles Clinic and Research Institute
Los Angeles, California, 90025
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Mays Cancer Center
San Antonio, Texas, 78229
WA Uni School Of Med
St Louis, Missouri, 63110
Germany7 sites
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Bochum, 44791
Novartis Investigative Site
Dresden, 01307
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Frankfurt am Main, Hesse, 60488
Novartis Investigative Site
Hamburg, 20249
Novartis Investigative Site
Ulm, 89081
Japan5 sites
Novartis Investigative Site
Kashiwa, Chiba, 277 8577
Novartis Investigative Site
Kawasaki, Kanagawa, 216-8511
Novartis Investigative Site
Nagoya, Aichi-ken, 464 8681
Novartis Investigative Site
Osaka, Osaka, 541-8567
Novartis Investigative Site
Toyama, 930-0194
Spain5 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
Madrid, 28040
Novartis Investigative Site
Sabadell, Barcelona, 08208
Novartis Investigative Site
Santander, Cantabria, 39008
Canada4 sites
Novartis Investigative Site
Brampton, Ontario, L6R 3J7
Novartis Investigative Site
Cambridge, Ontario, N1R 3G2
Novartis Investigative Site
Montreal, Quebec, H2W 1T8
Novartis Investigative Site
Montreal, Quebec, H3T 1E2
Australia3 sites
Novartis Investigative Site
Adelaide, South Australia, 5000
Novartis Investigative Site
Bendigo, Victoria, 3550
Novartis Investigative Site
Perth, Western Australia, 6009
Belgium3 sites
Novartis Investigative Site
Brussels, 1000
Novartis Investigative Site
Brussels, 1200
Novartis Investigative Site
Leuven, 3000
Czechia3 sites
Novartis Investigative Site
Brno, Czech Republic, 656 53
Novartis Investigative Site
Hradec Králové, CZE, 500 05
Novartis Investigative Site
Prague, 140 59
France3 sites
Novartis Investigative Site
Avignon, 84082
Novartis Investigative Site
Créteil, 94010
Novartis Investigative Site
Nantes, 44093
Italy3 sites
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Milan, MI, 20162
Novartis Investigative Site
Rozzano, MI, 20089
United Kingdom3 sites
Novartis Investigative Site
Aberdeen, Grampian Region, AB25 2ZN
Novartis Investigative Site
Cambridge, CB2 0QQ
Novartis Investigative Site
Oxford, OX3 7LE
Hong Kong2 sites
Novartis Investigative Site
Pokfulam
Novartis Investigative Site
Shatin
Israel2 sites
Novartis Investigative Site
Haifa, 3109601
Novartis Investigative Site
Petah Tikva, 4941492
Taiwan2 sites
Novartis Investigative Site
Tainan, 70403
Novartis Investigative Site
Taipei, 10002
About this study
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)
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.
Read the 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.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- NIS793, Bevacizumab, Modified FOLFOX6, FOLFIRI, Tislelizumab
- Keywords
- NIS793, metastatic colorectal cancer, colorectal cancer, transforming growth factor βeta (TGF-β), anti PD-1 monoclonal antibody
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NIS793Drug
Investigational drug NIS793 will be administered intravenously (IV) at the dose and schedule determined in the safety run-in part.
BevacizumabDrug
Bevacizumab will be administered IV
Modified FOLFOX6Drug
Also called 5FU+Leucovorin+Oxaliplatin
5-fluorouracil [continuous infusion], leucovorin [administered IV] (or levoleucovorin [administered IV]), and oxaliplatin [administered IV]
FOLFIRIDrug
Also called 5FU+Leucovorin+Irinotecan
5-fluorouracil [continuous infusion], leucovorin [administered IV] (or levoleucovorin [administered IV]), and irinotecan [administered IV]
TislelizumabDrug
Also called VDT482
Investigational drug tislelizumab will be administered intravenously (IV).
| Study group | Role | What they receive |
|---|---|---|
| Safety run-in: NIS793+SOC (Investigational arm 1) | Experimental | 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 Receives: Drug: NIS793; Drug: Bevacizumab; Drug: Modified FOLFOX6; Drug: FOLFIRI |
| Expansion: NIS793+SOC (Investigational arm 1) | Experimental | 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 Receives: Drug: NIS793; Drug: Bevacizumab; Drug: Modified FOLFOX6; Drug: FOLFIRI |
| Expansion: SOC (control arm) | Active comparator | 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) Receives: Drug: Bevacizumab; Drug: Modified FOLFOX6; Drug: FOLFIRI |
| Safety run-in: NIS793+Tislelizumab+SOC (Investigational arm 2) | Experimental | 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. Receives: Drug: NIS793; Drug: Bevacizumab; Drug: Modified FOLFOX6; Drug: FOLFIRI; Drug: Tislelizumab |
| Expansion: NIS793+Tislelizumab+SOC (Investigational arm 2) | Experimental | 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 Receives: Drug: NIS793; Drug: Bevacizumab; Drug: Modified FOLFOX6; Drug: FOLFIRI; Drug: Tislelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 4 weeks
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.
Measured: From randomization up to disease progression or death, assessed up to approximately 12 months
Secondary outcomes (23)
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
Measured: Up to approximately 12 months
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)
Measured: Upto approximately 12 months
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
Measured: Up to approximately 12 months
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.
Measured: From enrollment up to disease progression or death, assessed up to approximately 12 months
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
Measured: Up to approximately 12 months
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
Measured: Up to approximately 12 months
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
Measured: From first documented response up to disease progression or death, assessed up to approximately 12 months
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.
Measured: From enrollment up to death, assessed up to approximately 12 months
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.
Measured: From enrollment up to first documented response, assessed up to approximately 12 months
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
Measured: Up to approximately 12 months
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)
Measured: Up to approximately 12 months
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
Measured: Up to approximately 12 months
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
Measured: Up to approximately 12 months
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
Measured: Up to approximately 12 months
Expansion: 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
Measured: From first documented response up to disease progression or death, assessed up to approximately 12 months
Expansion part: Overall Survival (OS)
OS is defined as the time from the date of enrollment to date of death due to any cause.
Measured: From randomization up to death, assessed up to approximately 12 months
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.
Measured: From enrollment up to first documented response, assessed up to approximately 12 months
Maximum concentration (Cmax) of NIS793
Blood samples will be collected at indicated time-points for analysis of Cmax of NIS793
Measured: From the date of first study drug intake up to approximately 12 months
Maximum concentration (Cmax) of tislelizumab
Blood samples will be collected at indicated time-points for analysis of Cmax of tislelizumab
Measured: From the date of first study drug intake up to approximately 12 months
Trough Concentration (Ctrough) of NIS793
Blood samples will be collected at indicated time-points for analysis of Ctrough of NIS793
Measured: From the date of first study drug intake up to approximately 12 months
Trough Concentration (Ctrough) tislelizumab
Blood samples will be collected at indicated time-points for analysis of Ctrough of tislelizumab
Measured: From the date of first study drug intake up to approximately 12 months
Antidrug antibodies (ADA) at baseline
Prevalence of ADA (anti-NIS793, anti-tislelizumab) at baseline is defined as the proportion of participants who have an ADA positive result at baseline
Measured: Baseline
ADA incidence on treatment
Incidence of ADA (anti-NIS793, 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)
Measured: From the date of first study drug intake up to approximately 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2021
- Study start15 Nov 2021
- Primary completion20 Jan 2025
- Study completion20 Jan 2025
Why it stopped: The study was terminated early due to the halt of NIS793 treatment and urgent safety measures issued in July and August 2023, respectively, as continued evaluation of Standard of Care alone will not support the trial's purpose.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 204 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04952753
- Sponsor's protocol ID
- CNIS793E12201
- Other IDs
- 2021-000553-40
- Acronym
- daNIS-3
- Status last verified
- Mar 2025
- First submitted
- 28 Jun 2021
- Last updated
- 26 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04952753
- Acronym / sponsor ID
- daNIS-3 / CNIS793E12201
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- NIS793, metastatic colorectal cancer, colorectal cancer, transforming growth factor βeta (TGF-β), anti PD-1 monoclonal antibody
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated early due to the halt of NIS793 treatment and urgent safety measures issued in July and August 2023, respectively, as continued evaluation of Standard of Care alone will not support the trial's purpose.
- Enrolment
- 204 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 15 Nov 2021 (actual)
- Primary completion
- 20 Jan 2025 (actual)
- Study completion
- 20 Jan 2025 (actual)
- First posted
- 7 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Safety run-in: NIS793+SOC (Investigational arm 1) | Experimental | Drug: NIS793, Drug: Bevacizumab, Drug: Modified FOLFOX6, Drug: FOLFIRIIn 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 |
| Expansion: NIS793+SOC (Investigational arm 1) | Experimental | Drug: NIS793, Drug: Bevacizumab, Drug: Modified FOLFOX6, Drug: FOLFIRIIn 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 |
| Expansion: SOC (control arm) | Active comparator | Drug: Bevacizumab, Drug: Modified FOLFOX6, Drug: FOLFIRIIn 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) |
| Safety run-in: NIS793+Tislelizumab+SOC (Investigational arm 2) | Experimental | Drug: NIS793, Drug: Bevacizumab, Drug: Modified FOLFOX6, Drug: FOLFIRI, Drug: TislelizumabIn 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. |
| Expansion: NIS793+Tislelizumab+SOC (Investigational arm 2) | Experimental | Drug: NIS793, Drug: Bevacizumab, Drug: Modified FOLFOX6, Drug: FOLFIRI, Drug: TislelizumabIn 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 |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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 (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NIS793Investigational drug NIS793 will be administered intravenously (IV) at the dose and schedule determined in the safety run-in part. | Drug | Expansion: NIS793+SOC (Investigational arm 1), Expansion: NIS793+Tislelizumab+SOC (Investigational arm 2), Safety run-in: NIS793+SOC (Investigational arm 1), Safety run-in: NIS793+Tislelizumab+SOC (Investigational arm 2) |
| BevacizumabBevacizumab will be administered IV | Drug | Expansion: NIS793+SOC (Investigational arm 1), Expansion: NIS793+Tislelizumab+SOC (Investigational arm 2), Expansion: SOC (control arm), Safety run-in: NIS793+SOC (Investigational arm 1), Safety run-in: NIS793+Tislelizumab+SOC (Investigational arm 2) |
| Modified FOLFOX6Also: 5FU+Leucovorin+Oxaliplatin5-fluorouracil [continuous infusion], leucovorin [administered IV] (or levoleucovorin [administered IV]), and oxaliplatin [administered IV] | Drug | Expansion: NIS793+SOC (Investigational arm 1), Expansion: NIS793+Tislelizumab+SOC (Investigational arm 2), Expansion: SOC (control arm), Safety run-in: NIS793+SOC (Investigational arm 1), Safety run-in: NIS793+Tislelizumab+SOC (Investigational arm 2) |
| FOLFIRIAlso: 5FU+Leucovorin+Irinotecan5-fluorouracil [continuous infusion], leucovorin [administered IV] (or levoleucovorin [administered IV]), and irinotecan [administered IV] | Drug | Expansion: NIS793+SOC (Investigational arm 1), Expansion: NIS793+Tislelizumab+SOC (Investigational arm 2), Expansion: SOC (control arm), Safety run-in: NIS793+SOC (Investigational arm 1), Safety run-in: NIS793+Tislelizumab+SOC (Investigational arm 2) |
| TislelizumabAlso: VDT482Investigational drug tislelizumab will be administered intravenously (IV). | Drug | Expansion: NIS793+Tislelizumab+SOC (Investigational arm 2), Safety run-in: NIS793+Tislelizumab+SOC (Investigational arm 2) |
Primary outcome
Safety run-in: Percentage of participants with dose limiting toxicities (DLTs) during the first cycle (4 weeks) of treatment.
Time frame: Up to 4 weeks
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
Time frame: From randomization up to disease progression or death, assessed up to approximately 12 months
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.
23 secondary outcomes
Safety run-in: Percentage of participants with Adverse Events (AEs)
Time frame: Up to approximately 12 months
Safety run-in: Percentage of participants with dose interruptions and dose reductions of investigational drug
Time frame: Upto approximately 12 months
Safety run-in: Dose intensity of investigational drug
Time frame: Up to approximately 12 months
Safety run-in: PFS by investigator assessment per RECIST 1.1
Time frame: From enrollment up to disease progression or death, assessed up to approximately 12 months
Safety run-in: Overall response rate (ORR) by investigator assessment per RECIST 1.1
Time frame: Up to approximately 12 months
Safety run-in: Disease control rate (DCR) by investigator assessment per RECIST 1.1
Time frame: Up to approximately 12 months
Safety run-in: Duration of response (DOR) by investigator assessment per RECIST 1.1
Time frame: From first documented response up to disease progression or death, assessed up to approximately 12 months
Safety run-in part: Overall Survival (OS)
Time frame: From enrollment up to death, assessed up to approximately 12 months
Safety run-in: Time to response (TTR) by investigator assessment per RECIST 1.1
Time frame: From enrollment up to first documented response, assessed up to approximately 12 months
Expansion: Percentage of participants with Adverse Events (AEs)
Time frame: Up to approximately 12 months
Expansion part: Percentage of participants with dose interruptions and dose reductions of investigational drug
Time frame: Up to approximately 12 months
Expansion: Dose intensity of investigational drug
Time frame: Up to approximately 12 months
Expansion: Overall response rate (ORR) by investigator assessment per RECIST 1.1
Time frame: Up to approximately 12 months
Expansion: Disease control rate (DCR) by investigator assessment per RECIST 1.1
Time frame: Up to approximately 12 months
Expansion: Duration of response (DOR) by investigator assessment per RECIST 1.1
Time frame: From first documented response up to disease progression or death, assessed up to approximately 12 months
Expansion part: Overall Survival (OS)
Time frame: From randomization up to death, assessed up to approximately 12 months
Expansion: Time to response (TTR) by investigator assessment per RECIST 1.1
Time frame: From enrollment up to first documented response, assessed up to approximately 12 months
Maximum concentration (Cmax) of NIS793
Time frame: From the date of first study drug intake up to approximately 12 months
Maximum concentration (Cmax) of tislelizumab
Time frame: From the date of first study drug intake up to approximately 12 months
Trough Concentration (Ctrough) of NIS793
Time frame: From the date of first study drug intake up to approximately 12 months
Trough Concentration (Ctrough) tislelizumab
Time frame: From the date of first study drug intake up to approximately 12 months
Antidrug antibodies (ADA) at baseline
Time frame: Baseline
ADA incidence on treatment
Time frame: From the date of first study drug intake up to approximately 12 months
Results and safety
The study was stopped early (reason given: The study was terminated early due to the halt of NIS793 treatment and urgent safety measures issued in July and August 2023, respectively, as continued evaluation of Standard of Care alone will not support the trial's purpose.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2025.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
55 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NIS793, Bevacizumab and Modified FOLFOX6 in people with Metastatic Colorectal Cancer, run by Novartis Pharmaceuticals at 55 sites in 17 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 55 sites in United States, Germany, Japan, Spain, Canada and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The study was terminated early due to the halt of NIS793 treatment and urgent safety measures issued in July and August 2023, respectively, as continued evaluation of Standard of Care alone will not support the trial's purpose.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety run-in: Percentage of participants with dose limiting toxicities (DLTs) during the first cycle (4 weeks) of treatment. (time frame: Up to 4 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2025.