Recruiting
Phase 3

Zanzalintinib & Pembrolizumab

Sponsor:

Exelixis

Code:

NCT07750158

Conditions

Colorectal Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Zanzalintinib

Pembrolizumab (+) Berahyaluronidase alfa

Placebo

Study Details

Brief summary:

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

Conditions

Colorectal Cancer

Study ID

NCT07750158

Start date

Aug 25, 2026

Status verified date

Sep, 2026

Completion date

Apr 5, 2030

Anticipated

Primary completion date

Apr 5, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

600 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Zanzalintinib + Pembrolizumab (+) Berahyaluronidase alfa

Participants will receive zanzalintinib in combination with pembrolizumab (+) berahyaluronidase alfa for up to 2 years.

experimental: Zanzalintinib Monotherapy

Participants will receive zanzalintinib for up to 2 years.

placebo comparator: Placebo

Participants will receive placebo to match zanzalintinib for up to 2 years.

Interventions

Zanzalintinib

Oral tablets administered once daily.

Pembrolizumab (+) Berahyaluronidase alfa

Pembrolizumab + berahyaluronidase alfa fixed-dose combination administered via subcutaneous (SC) injection once every 3 weeks (Q3W).

Placebo

Placebo to match zanzalintinib oral tablets administered once daily.

Primary outcome measure

  • Disease-Free Survival (DFS) in Zanzalintinib + MK-3475A Versus Placebo as Assessed by the Investigator [ Time Frame: Up to 24 months ]
  • DFS in Zanzalintinib Monotherapy Versus Placebo as Assessed by the Investigator [ Time Frame: Up to 24 months ]

Central Contacts and Locations

Central contacts

Exelixis Clinical Trials

1-888-393-5494druginfo@exelixis.com

Locations

Oncology Hematology West, PC dba Nebraska Cancer Specialists - Council Bluffs

Recruiting

Council Bluffs, Iowa, United States, 51503

Oncology Hematology West, PC dba Nebraska Cancer Specialists - Grand Island

Recruiting

Grand Island, Nebraska, United States, 68803

Oncology Hematology West, PC dba Nebraska Cancer Specialists - Regional

Recruiting

Grand Island, Nebraska, United States, 68803

Oncology Hematology West, PC dba Nebraska Cancer Specialists - Methodist

Recruiting

Omaha, Nebraska, United States, 68114

Oncology Hematology West, PC dba Nebraska Cancer Specialists - Bergan

Recruiting

Omaha, Nebraska, United States, 68124

Oncology Hematology West, PC dba Nebraska Cancer Specialists - Legacy

Recruiting

Omaha, Nebraska, United States, 68130

Oncology Hematology West, PC dba Nebraska Cancer Specialists - Papillion

Recruiting

Papillion, Nebraska, United States, 68046

Astera Cancer Care

Recruiting

Bridgewater, New Jersey, United States, 08807

Astera Cancer Care

Recruiting

East Brunswick, New Jersey, United States, 08816

Astera Cancer Care

Recruiting

Edison, New Jersey, United States, 08820

Astera Cancer Care

Recruiting

Monroe, New Jersey, United States, 08831

Astera Cancer Care

Recruiting

Somerset, New Jersey, United States, 08873

Astera Cancer Care

Recruiting

Toms River, New Jersey, United States, 08757

More Information

Sponsor

Exelixis

Last update posted

Sep 21, 2026

Last verified

Sep, 2026

Keywords

  • Molecular Residual Disease
  • Stage II
  • Stage III
  • Circulating Tumor Deoxyribose Nucleic Acid (ctDNA) Positive
  • Signatera Test
  • Recurrence Prevention
  • Early Stage Resectable Colorectal Cancer (CRC)
  • Curative-Intent Therapy
  • Microsatellite-Stable (MSS)
  • Microsatellite Instability (MSI) - Low
  • Mismatch Repair Proficient (pMMR)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-24. This information was provided to ClinicalTrials.gov by Exelixis on 2026-09-21. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.