Colorectal Cancer
Conditions
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)
Brief summary
The primary objective of this study is to evaluate the effectiveness of zanzalintinib + Pembrolizumab (+) berahyaluronidase alfa and zanzalintinib alone compared with placebo.
Interventions
DRUGZanzalintinib
Oral tablets administered once daily.
BIOLOGICALPembrolizumab (+) Berahyaluronidase alfa
Pembrolizumab + berahyaluronidase alfa fixed-dose combination administered via subcutaneous (SC) injection once every 3 weeks (Q3W).
DRUGPlacebo
Placebo to match zanzalintinib oral tablets administered once daily.
Sponsors
Exelixis
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
| Proportion of Participants with Treatment Emergent Adverse Events (TEAEs) | Up to 24 months |
Countries
United States
Contacts
CONTACTExelixis Clinical Trials
STUDY_DIRECTORMedical Director
Exelixis
Outcome results
None listed