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Zanzalintinib Alone or in Combination With Pembrolizumab and Berahyaluronidase Alfa in Participants With Colorectal Cancer With Molecular Residual Disease

RecruitingPhase 3

Randomized Phase 3 Study of Zanzalintinib ± Subcutaneous Pembrolizumab and Berahyaluronidase Alfa (MK-3475A) Versus Placebo in Participants With Colorectal Cancer With Stage II/III Molecular Residual Disease Following Definitive Therapy

Who can join

Ages 18 and older · All sexes

Full eligibility criteria
Key Inclusion Criteria:

* Histologically confirmed diagnosis of Stage II or III adenocarcinoma of colon or rectum.
* Documented local MSI and/or mismatch repair (MMR) test result demonstrating MSS, MSI-low, or pMMR status.
* Colon or rectal cancer with completed definitive therapy.
* ctDNA-positive based on local testing using the Natera Signatera tissue-informed molecular residual disease (MRD) assay.
* No radiographic evidence of disease, as confirmed by a negative baseline computed tomography (CT) of the chest, abdomen, and pelvis (CAP), or CT of chest and magnetic resonance imaging (MRI) of abdomen/pelvis.

Key Exclusion Criteria:

* History of solid organ or allogeneic stem cell transplant.
* Known additional malignancy that is progressing or has required active treatment within the past 2 years.
* Prior treatment with immune checkpoint inhibitors (ICIs) or Vascular endothelial growth factor receptor (VEGFR) inhibitors.
* History of CRC requiring systemic anticancer therapy prior to the definitive therapy.
* Use of systemic anticancer therapy (including investigational therapy) or radiation therapy after the completion of definitive therapy.
* Administration of a live, attenuated vaccine within 30 days of randomization and during treatment.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

About the study

The primary objective of this study is to evaluate the effectiveness of zanzalintinib + Pembrolizumab (+) berahyaluronidase alfa and zanzalintinib alone compared with placebo.

What is being tested

Sponsor: Exelixis · Participants: 600 · Started: Aug 25, 2026

Contact the study team

Official record on ClinicalTrials.gov — NCT07750158

Locations in the U.S.

IowaOncology Hematology West, PC dba Nebraska Cancer Specialists - Council Bluffs, Council Bluffs
NebraskaOncology Hematology West, PC dba Nebraska Cancer Specialists - Grand Island, Grand Island
Oncology Hematology West, PC dba Nebraska Cancer Specialists - Regional, Grand Island
Oncology Hematology West, PC dba Nebraska Cancer Specialists - Bergan, Omaha
Oncology Hematology West, PC dba Nebraska Cancer Specialists - Legacy, Omaha
Oncology Hematology West, PC dba Nebraska Cancer Specialists - Methodist, Omaha
Oncology Hematology West, PC dba Nebraska Cancer Specialists - Papillion, Papillion
New JerseyAstera Cancer Care, Bridgewater
Astera Cancer Care, East Brunswick
Astera Cancer Care, Edison
Astera Cancer Care, Monroe
Astera Cancer Care, Somerset
Astera Cancer Care, Toms River

Conditions

From ClinicalTrials.gov, data retrieved Oct 2, 2026. Each study sets its own eligibility; the study team decides who can join.