A Randomized, Double-Blind, Phase 3 Study of Standard-of-Care Chemotherapy and Bevacizumab With or Without INCA33890 in the First-Line Treatment of Metastatic Microsatellite Stable Colorectal Cancer

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Investigational drug late phase More information Active drug More information Moderate burden on patient More information

Trial Details

Sponsor: Incyte Corporation (industry)

Phase: 3

Start date: Dec. 16, 2025

Planned enrollment: 700

Trial ID: NCT07284849
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More trial details at ClinicalTrials.gov More info

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Goal: To determine whether adding INCA33890 to first-line FOLFOX plus bevacizumab improves efficacy versus FOLFOX plus bevacizumab alone in metastatic microsatellite-stable colorectal cancer, while characterizing safety and patient-reported outcomes.

Patients: Adults with stage IV colorectal adenocarcinoma not amenable to curative resection, microsatellite stable by historical testing, with measurable disease per RECIST v1.1, ECOG 0–1, and adequate organ function. No prior systemic therapy for unresectable/metastatic disease is allowed (prior adjuvant/neoadjuvant therapy permitted if no recurrence within 12 months). Key exclusions include MSI-H/dMMR, BRAF V600E mutation, untreated/progressing CNS metastases, recent other malignancy, prior PD-(L)1/other checkpoint inhibitor exposure within 3 years, active autoimmune disease requiring systemic treatment within 2 years, significant uncontrolled comorbidity, and prior organ transplant.

Design: Phase 3, randomized, double-blind, placebo-controlled, multicenter first-line study with planned enrollment of approximately 700 participants. Participants are assigned to receive standard chemotherapy and bevacizumab with either INCA33890 or placebo, with investigator-assessed tumor response per RECIST v1.1 and follow-up for survival, safety, and quality of life.

Treatments: Experimental arm: INCA33890 in combination with bevacizumab and FOLFOX at protocol-defined doses. Control arm: placebo in combination with bevacizumab and FOLFOX. FOLFOX plus bevacizumab represents a standard first-line regimen for metastatic colorectal cancer in appropriate patients. INCA33890 is an investigational bispecific antibody designed to target PD-1 and TGFβR2, aiming to couple checkpoint inhibition with localized blockade of TGF-β signaling in PD-1–expressing cells to mitigate immunosuppressive signaling while limiting systemic TGF-β pathway inhibition. Early clinical experience reported in heavily pretreated metastatic MSS colorectal cancer showed objective responses (reported ORR about 15% in an expansion cohort), supporting evaluation in the first-line setting. Across early-phase experience, the safety profile was described as manageable, with commonly reported treatment-related events including fatigue, pruritus, and infusion reactions, and immune-related toxicities broadly consistent with PD-1–based therapies.

Outcomes: The primary endpoint is progression-free survival (time from randomization to RECIST v1.1 progression per investigator assessment or death), assessed up to 3 years. Key secondary endpoints include overall survival (up to 4 years), objective response rate, duration of response, treatment-emergent adverse events including events leading to dose interruption/reduction/discontinuation, and patient-reported outcomes/health-related quality of life using EQ-5D-5L, EORTC QLQ-C30, and FCSI-9 (up to 4 years).

Burden on patient: Moderate burden. Treatment requires intravenous multi-agent chemotherapy (FOLFOX) and bevacizumab with blinded intravenous study drug (INCA33890 or placebo), implying frequent clinic visits typical of first-line mCRC infusion regimens, routine laboratory monitoring, and standard serial imaging for RECIST assessments over time. Additional burden beyond usual care is expected from blinding-related procedures and regular quality-of-life questionnaires; intensive phase 1–style pharmacokinetic sampling or mandatory repeat biopsies are not described in the provided information, suggesting no major high-burden research procedures beyond standard metastatic colorectal cancer trial monitoring.

Last updated: Feb 2026

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Ravenna, 48100, Italy

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Kōtoku, 135-8550, Japan

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Chiba, 260-8717, Japan

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Akashi-shi, 673-8558, Japan

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Kita-gun, 761-0793, Japan

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Kobe, 650-0047, Japan

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Nankoku-shi, 783-8505, Japan

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Osaka, 541-8567, Japan

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Hidaka-shi, 350-1298, Japan

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Kawasaki-shi, 216-8511, Japan

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Suita-shi, 565-0871, Japan

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Maastricht, 6229 HX, Netherlands

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Oslo, 00405, Norway

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Warsaw, 01-748, Poland

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Siedlce, 08-110, Poland

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Warsaw, 02-781, Poland

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Jelenia Góra, 58-506, Poland

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Suwon, 443-380, South Korea

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Seoul, 05505, South Korea

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Seoul, 04763, South Korea

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Seoul, 02841, South Korea

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Goyang-si, 10408, South Korea

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Changwon-si, 51353, South Korea

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Seongnam, 13620, South Korea

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Seoul, 03080, South Korea

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Seoul, 03722, South Korea

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Seoul, 06591, South Korea

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Seoul, 03312, South Korea

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Complejo Hospitalario Universitario Insular-Materno Infantil

Las Palmas de Gran Canaria, 35016, Spain

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Hospital Clinic Barcelona Main

Barcelona, 08036, Spain

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Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

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Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

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Barcelona, 08035, Spain

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Badalona, 08916, Spain

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Terrassa, 08221, Spain

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Madrid, 28041, Spain

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Madrid, 28040, Spain

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Hospital Universitario Marques de Valdecilla

Santander, 39012, Spain

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Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

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Hospital Universitario Puerta de Hierro de Majadahonda

Majadahonda, 28220, Spain

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Pamplona, 31008, Spain

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Hospital de La Santa Creu I Sant Pau

Barcelona, 08041, Spain

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Son Espases University Hospital

Palma de Mallorca, 07120, Spain

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Chuv, Lausanne University Hospital

Lausanne, 01005, Switzerland

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Hoch Health Ostschweiz

Sankt Gallen, 09007, Switzerland

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Inselspital - Universitaetsspital Bern

Bern, 03010, Switzerland

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Barts Hospital

London, EC1A 7BE, United Kingdom

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Bristol Haematology and Oncology Centre

Bristol, BS2 8ED, United Kingdom

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Guys Hospital

London, SE1 9RT, United Kingdom

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Kent Oncology Centre - Maidstone Hospital

Maidstone, ME16 9QQ, United Kingdom

No email / No phone

Status: Not yet recruiting

St James University Hospital

Leeds, LS9 7TF, United Kingdom

No email / No phone

Status: Not yet recruiting

The Christie Nhs Foundation Trust Uk

Manchester, M20 4BX, United Kingdom

No email / No phone

Status: Not yet recruiting

The Royal Marsden Nhs Foundation Trust - Sutton

Sutton, SM2 5PT, United Kingdom

No email / No phone

Status: Not yet recruiting

Velindre Cancer Centre

Cardiff, CF14 2TL, United Kingdom

No email / No phone

Status: Not yet recruiting

The University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

No email / No phone

Status: Not yet recruiting

Long Beach Medical Center

Long Beach, California, 90806, United States

No email / No phone

Status: Not yet recruiting

Los Angeles Cancer Network

Anaheim, California, 92801, United States

No email / No phone

Status: Not yet recruiting

Providence Medical Foundation

Fullerton, California, 92835, United States

No email / No phone

Status: Not yet recruiting

Toi Clinical Research

Cerritos, California, 90703, United States

No email / No phone

Status: Not yet recruiting

University of California Los Angeles Health

Los Angeles, California, 90095, United States

No email / No phone

Status: Not yet recruiting

Hartford Hospital

Hartford, Connecticut, 06102, United States

No email / No phone

Status: Not yet recruiting

George Washington University

Washington D.C., District of Columbia, 20037, United States

No email / No phone

Status: Not yet recruiting

Advent Health

Orlando, Florida, 32804, United States

No email / No phone

Status: Not yet recruiting

Ascension Sacred Heart Pensacola

Pensacola, Florida, 32504, United States

No email / No phone

Status: Not yet recruiting

Florida Oncology & Hematology

Fort Myers, Florida, 33912, United States

No email / No phone

Status: Not yet recruiting

Orlando Health Cancer Institute Downtown Orlando

Orlando, Florida, 32806, United States

No email / No phone

Status: Not yet recruiting

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

No email / No phone

Status: Not yet recruiting

Tampa General Hospital-Cancer Institute

Tampa, Florida, 33606, United States

No email / No phone

Status: Not yet recruiting

University of Florida Health

Gainesville, Florida, 32610, United States

No email / No phone

Status: Not yet recruiting

Piedmont Cancer Institute

Locust Grove, Georgia, 30248, United States

No email / No phone

Status: Not yet recruiting

University of Hawaii Cancer Center

Honolulu, Hawaii, 96813-2402, United States

No email / No phone

Status: Not yet recruiting

St Lukes Mountain States Tumor Institute Msti Boise

Boise, Idaho, 83712, United States

No email / No phone

Status: Not yet recruiting

Endeavor Health

Evanston, Illinois, 60201, United States

No email / No phone

Status: Not yet recruiting

Springfield Clinic

Springfield, Illinois, 62702, United States

No email / No phone

Status: Not yet recruiting

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

No email / No phone

Status: Not yet recruiting

Community Health Network, Inc.

Indianapolis, Indiana, 46250, United States

No email / No phone

Status: Not yet recruiting

Hematology Oncology of Indiana

Indianapolis, Indiana, 46260, United States

No email / No phone

Status: Not yet recruiting

University of Iowa Hospital and Clinics

Iowa City, Iowa, 52242, United States

No email / No phone

Status: Not yet recruiting

Cancer Center For Blood Disorders A Division of American Oncology Partners P.A

Bethesda, Maryland, 20817, United States

No email / No phone

Status: Not yet recruiting

Saint Agnes Hospital

Baltimore, Maryland, 21229-5201, United States

No email / No phone

Status: Not yet recruiting

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

No email / No phone

Status: Not yet recruiting

Henry Ford Hospital

Detroit, Michigan, 48202, United States

No email / No phone

Status: Not yet recruiting

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

No email / No phone

Status: Not yet recruiting

St. Joseph Mercy Hospital

Ann Arbor, Michigan, 48106, United States

No email / No phone

Status: Not yet recruiting

Midamerica Cancer Care

Kansas City, Missouri, 64121, United States

No email / No phone

Status: Not yet recruiting

Missouri Cancer Associates

Columbia, Missouri, 65201, United States

No email / No phone

Status: Not yet recruiting

Oncology Hematology Associates

Springfield, Missouri, 65807, United States

No email / No phone

Status: Not yet recruiting

Saint Luke'S Hospital of Kansas City

Kansas City, Missouri, 64111, United States

No email / No phone

Status: Not yet recruiting

Morristown Medical Center

Morristown, New Jersey, 07960, United States

No email / No phone

Status: Not yet recruiting

Presbyterian Healthcare Services

Albuquerque, New Mexico, 87113, United States

No email / No phone

Status: Not yet recruiting

Icahn School of Medicine At Mount Sinai

New York, New York, 10029, United States

No email / No phone

Status: Not yet recruiting

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

No email / No phone

Status: Not yet recruiting

Montefiore Einstein For Cancer Care

The Bronx, New York, 10461, United States

No email / No phone

Status: Not yet recruiting

Ny Cancer and Blood Specialists

Shirley, New York, 11967, United States

No email / No phone

Status: Not yet recruiting

University of Rochester

Rochester, New York, 14623-2327, United States

No email / No phone

Status: Not yet recruiting

Messino Cancer Center

Asheville, North Carolina, 28806, United States

No email / No phone

Status: Not yet recruiting

Oncology Specialists of Charlotte

Charlotte, North Carolina, 28207, United States

No email / No phone

Status: Not yet recruiting

The University of North Carolina At Chapel Hill

Chapel Hill, North Carolina, 27514, United States

No email / No phone

Status: Not yet recruiting

Ohio Health

Columbus, Ohio, 43214, United States

No email / No phone

Status: Not yet recruiting

Ohio State University-Arthur G James Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

No email / No phone

Status: Not yet recruiting

University of Cincinnati Cancer Institute

Cincinnati, Ohio, 45219, United States

No email / No phone

Status: Not yet recruiting

Allegheny General Hospital Cancer Institute

Pittsburgh, Pennsylvania, 15212, United States

No email / No phone

Status: Not yet recruiting

Alliance Cancer Specialists

Doylestown, Pennsylvania, 18901, United States

No email / No phone

Status: Not yet recruiting

Cancer Care Associates of York

York, Pennsylvania, 17403, United States

No email / No phone

Status: Not yet recruiting

Hillman Cancer Center

Monroeville, Pennsylvania, 15146, United States

No email / No phone

Status: Not yet recruiting

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17933, United States

No email / No phone

Status: Not yet recruiting

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

No email / No phone

Status: Not yet recruiting

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

No email / No phone

Status: Not yet recruiting

Ascension Seton Spclty Care Ctr

Austin, Texas, 78712, United States

No email / No phone

Status: Not yet recruiting

Baylor Scott & White Health

Temple, Texas, 76508, United States

No email / No phone

Status: Not yet recruiting

Md Anderson Cancer Center

Houston, Texas, 77030, United States

No email / No phone

Status: Not yet recruiting

University of Texas Southwestern Medical Center

Dallas, Texas, 75235, United States

No email / No phone

Status: Not yet recruiting

Vandalia Health Charleston Area Medical Center

Charleston, West Virginia, 25304, United States

No email / No phone

Status: Not yet recruiting

West Virginia University Cancer Institute

Morgantown, West Virginia, 26506, United States

No email / No phone

Status: Not yet recruiting

Flinders Medical Centre

Bedford Park, South Australia, 05042, Australia

No email / No phone

Status: Withdrawn

Rigshospitalet

Copenhagen, 02100, Denmark

No email / No phone

Status: Withdrawn

Institut Paoli Calmettes

Marseille, 13273, France

No email / No phone

Status: Withdrawn

Haematologisch-Onkologischen Praxis Eppendorf (Hope)

Hamburg, 20249, Germany

No email / No phone

Status: Withdrawn

Universitaetsklinikum Leipzig Aoer

Leipzig, 04103, Germany

No email / No phone

Status: Withdrawn

Agostino Gemelli Policlinico Universitario

Rome, 00168, Italy

No email / No phone

Status: Withdrawn

Amsterdam Umc

Amsterdam, 1081 HV, Netherlands

No email / No phone

Status: Withdrawn

Netherlands Cancer Institute Antoni Van Leeuwenhoek Ziekenhuis

Amsterdam, 1066 CX, Netherlands

No email / No phone

Status: Withdrawn

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

No email / No phone

Status: Withdrawn

Uniwersytecki Szpital Kliniczny Im. Fryderyka Chopina W Rzeszowie

Rzeszów, 35-055, Poland

No email / No phone

Status: Withdrawn

Hospital General Universitario de Valencia

Valencia, 46014, Spain

No email / No phone

Status: Withdrawn

Ironwood Cancer & Research Centers

Chandler, Arizona, 85224-5665, United States

No email / No phone

Status: Withdrawn

H. Lee Moffitt Cancer Center and Research Institute Hospital

Tampa, Florida, 33612-9497, United States

No email / No phone

Status: Withdrawn

Iu Simon Cancer Center

Indianapolis, Indiana, 46202, United States

No email / No phone

Status: Withdrawn

Ochsner Clinic Foundation Ocf Ochsner Cancer Institute Oci

New Orleans, Louisiana, 70121, United States

No email / No phone

Status: Withdrawn

New England Cancer Specialists

Scarborough, Maine, 04074-7171, United States

No email / No phone

Status: Withdrawn

University of Michigan

Ann Arbor, Michigan, 48109, United States

No email / No phone

Status: Withdrawn

Monter Cancer Center

New Hyde Park, New York, 11042, United States

No email / No phone

Status: Withdrawn

Sidney Kimmel Comprehensive Cancer Center

Philadelphia, Pennsylvania, 19107, United States

No email / No phone

Status: Withdrawn

Sarah Cannon Research Institute Scri Oncology Partners

Nashville, Tennessee, 37203, United States

No email / No phone

Status: Withdrawn

Tennessee Oncology, Pllc

Nashville, Tennessee, 37203, United States

No email / No phone

Status: Withdrawn

Inova Schar Cancer Institute

Fairfax, Virginia, 22031-4867, United States

No email / No phone

Status: Withdrawn

Cancer Care Northwest

Spokane, Washington, 99202, United States

No email / No phone

Status: Withdrawn

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

No email / No phone

Status: Withdrawn

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