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

NCT04952753 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: CNIS793E122012021-000553-40
• Study Type: interventional
• Target: 204
• Locations: 17 countries
• Sites: 55

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.

Conditions

Metastatic Colorectal Cancer

Keywords

NIS793; metastatic colorectal cancer; colorectal cancer; transforming growth factor βeta (TGF-β); anti PD-1 monoclonal antibody

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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)

  Up to approximately 12 months

• Safety run-in: Percentage of participants with dose interruptions and dose reductions of investigational drug

  Upto approximately 12 months

• Safety run-in: Dose intensity of investigational drug

  Up to approximately 12 months

• Safety run-in: PFS by investigator assessment per RECIST 1.1

  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

  Up to approximately 12 months

Study Arms (5)

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

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

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)

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.

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

Drug: NIS793; Drug: Bevacizumab; Drug: Modified FOLFOX6; Drug: FOLFIRI; Drug: Tislelizumab

Interventions

NIS793 DRUG

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

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)

Bevacizumab DRUG

Bevacizumab will be administered IV

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 FOLFOX6 DRUG

5-fluorouracil \[continuous infusion\], leucovorin \[administered IV\] (or levoleucovorin \[administered IV\]), and oxaliplatin \[administered IV\]

Also known as: 5FU+Leucovorin+Oxaliplatin

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)

FOLFIRI DRUG

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

Also known as: 5FU+Leucovorin+Irinotecan

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)

Tislelizumab DRUG

Investigational drug tislelizumab will be administered intravenously (IV).

Also known as: VDT482

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

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (55)

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

University of Michigan Medical

Ann Arbor, Michigan, 48109-0331, United States

Location

WA Uni School Of Med

St Louis, Missouri, 63110, United States

Location

Astera Cancer Center

East Brunswick, New Jersey, 08816, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Uni Of TX MD Anderson Cancer Cntr

Houston, Texas, 77030, United States

Location

Mays Cancer Center

San Antonio, Texas, 78229, United States

Location

Novartis Investigative Site

Adelaide, South Australia, 5000, Australia

Location

Novartis Investigative Site

Bendigo, Victoria, 3550, Australia

Location

Novartis Investigative Site

Perth, Western Australia, 6009, Australia

Location

Novartis Investigative Site

Brussels, 1000, Belgium

Location

Novartis Investigative Site

Brussels, 1200, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Brampton, Ontario, L6R 3J7, Canada

Location

Novartis Investigative Site

Cambridge, Ontario, N1R 3G2, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H2W 1T8, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H3T 1E2, Canada

Location

Novartis Investigative Site

Brno, Czech Republic, 656 53, Czechia

Location

Novartis Investigative Site

Hradec Králové, CZE, 500 05, Czechia

Location

Novartis Investigative Site

Prague, 140 59, Czechia

Location

Novartis Investigative Site

Avignon, 84082, France

Location

Novartis Investigative Site

Créteil, 94010, France

Location

Novartis Investigative Site

Nantes, 44093, France

Location

Novartis Investigative Site

Frankfurt am Main, Hesse, 60488, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Bochum, 44791, Germany

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Hamburg, 20249, Germany

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

Novartis Investigative Site

Pokfulam, Hong Kong

Location

Novartis Investigative Site

Shatin, Hong Kong

Location

Novartis Investigative Site

Haifa, 3109601, Israel

Location

Novartis Investigative Site

Petah Tikva, 4941492, Israel

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Milan, MI, 20162, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 464 8681, Japan

Location

Novartis Investigative Site

Kashiwa, Chiba, 277 8577, Japan

Location

Novartis Investigative Site

Kawasaki, Kanagawa, 216-8511, Japan

Location

Novartis Investigative Site

Osaka, Osaka, 541-8567, Japan

Location

Novartis Investigative Site

Toyama, 930-0194, Japan

Location

Novartis Investigative Site

Singapore, 119074, Singapore

Location

Novartis Investigative Site

Seoul, 05505, South Korea

Location

Novartis Investigative Site

Sabadell, Barcelona, 08208, Spain

Location

Novartis Investigative Site

Santander, Cantabria, 39008, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

Madrid, 28040, Spain

Location

Novartis Investigative Site

Sankt Gallen, 9007, Switzerland

Location

Novartis Investigative Site

Tainan, 70403, Taiwan

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Novartis Investigative Site

Aberdeen, Grampian Region, AB25 2ZN, United Kingdom

Location

Novartis Investigative Site

Cambridge, CB2 0QQ, United Kingdom

Location

Novartis Investigative Site

Oxford, OX3 7LE, United Kingdom

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

NIS-793; Bevacizumab; IFL protocol; tislelizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2021
• First Posted: July 7, 2021
• Study Start: November 15, 2021
• Primary Completion: January 20, 2025
• Study Completion: January 20, 2025
• Last Updated: March 26, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

AU (3); JP (5); CA (4); ES (5); CH (1); BE (3); GB (3); HK (2); IL (2); IT (3); TW (2); US (7); KR (1); FR (3); SG (1); CZ (3); DE (7)