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
Trial Snapshot
- Phase
- Phase 3
- Status
- Not yet recruiting
- Sponsor
- Exelixis
- Enrollment
- 600
- Locations
- 13
- Primary Endpoint
- Disease-Free Survival (DFS) in Zanzalintinib + MK-3475A Versus Placebo as Assessed by the Investigator
Study Overview
Brief Summary
The primary objective of this study is to evaluate the effectiveness of zanzalintinib + Pembrolizumab (+) berahyaluronidase alfa and zanzalintinib alone compared with placebo.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, 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 Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
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.
Arms & Interventions
Zanzalintinib + MK-3475A
Participants will receive zanzalintinib in combination with MK-3475A (pembrolizumab + berahyaluronidase alfa) for up to 2 years.
Intervention: MK-34574 (Biological)
Placebo
Participants will receive placebo to match zanzalintinib for up to 2 years.
Intervention: Placebo (Drug)
Zanzalintinib + MK-3475A
Participants will receive zanzalintinib in combination with MK-3475A (pembrolizumab + berahyaluronidase alfa) for up to 2 years.
Intervention: Zanzalintinib (Drug)
Zanzalintinib Monotherapy
Participants will receive zanzalintinib for up to 2 years.
Intervention: Zanzalintinib (Drug)
Zanzalintinib + Pembrolizumab (+) Berahyaluronidase alfa
Participants will receive zanzalintinib in combination with pembrolizumab (+) berahyaluronidase alfa for up to 2 years.
Intervention: Zanzalintinib (Drug)
Zanzalintinib + Pembrolizumab (+) Berahyaluronidase alfa
Participants will receive zanzalintinib in combination with pembrolizumab (+) berahyaluronidase alfa for up to 2 years.
Intervention: Pembrolizumab (+) Berahyaluronidase alfa (Biological)
Outcomes
Primary Outcomes
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
Secondary Outcomes
- 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)