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

NCT07750158 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: XL092-316MK-3475A-G72
• Study Type: interventional
• Target: 600
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of this study is to evaluate the effectiveness of zanzalintinib + MK-3475A and zanzalintinib alone compared with placebo.

Conditions

Colorectal Cancer

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)

Outcome Measures

Primary Outcomes (2)

• Disease-Free Survival (DFS) in Zanzalintinib + MK-3475A Versus Placebo as Assessed by the Investigator

  Up to 24 months

• DFS in Zanzalintinib Monotherapy Versus Placebo as Assessed by the Investigator

  Up to 24 months

Secondary Outcomes (6)

• Proportion of Participants with ctDNA Clearance in Zanzalintinib + MK-3475A Versus Placebo

  Up to 24 months

• Proportion of Participants with ctDNA Clearance in Zanzalintinib Monotherapy Versus Placebo

  Up to 24 months

• Overall Survival (OS) in Zanzalintinib + MK-3475A Versus Placebo

  Up to 24 months

• OS in Zanzalintinib Monotherapy Versus Placebo

  Up to 24 months

• DFS in Zanzalintinib + MK-3475A Versus Zanzalintinib Monotherapy as Assessed by the Investigator

  Up to 24 months

Study Arms (3)

Zanzalintinib + MK-3475A

EXPERIMENTAL

Participants will receive zanzalintinib in combination with MK-3475A (pembrolizumab + berahyaluronidase alfa) for up to 2 years.

Drug: Zanzalintinib; Biological: MK-34574

Zanzalintinib Monotherapy

EXPERIMENTAL

Participants will receive zanzalintinib for up to 2 years.

Drug: Zanzalintinib

Placebo

EXPERIMENTAL

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

Drug: Placebo

Interventions

Zanzalintinib DRUG

Oral tablets administered once daily.

Also known as: XL092

Zanzalintinib + MK-3475A; Zanzalintinib Monotherapy

MK-34574 BIOLOGICAL

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

Also known as: KEYTRUDA QLEX™, KEYTRUDA SC

Zanzalintinib + MK-3475A

Placebo DRUG

Placebo to match zanzalintinib oral tablets administered once daily.

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Exelixis: lead
• Merck Sharp & Dohme LLC: collaborator

MeSH Terms

Conditions

Colorectal Neoplasms; Microsatellite Instability

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; Genomic Instability; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Medical Director

  Exelixis

  STUDY DIRECTOR

Central Study Contacts

Exelixis Clinical Trials

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This is a partially blinded trial: the arm of zanzalintinib + MK-3475A is an open-label arm; the arms of zanzalintinib monotherapy and placebo are blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2026
• First Posted: August 6, 2026
• Study Start: August 6, 2026
• Primary Completion (Estimated): April 5, 2030
• Study Completion (Estimated): April 5, 2030
• Last Updated: August 6, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share