NCT04963283

Study of Cabozantinib and Nivolumab in Refractory Metastatic Microsatellite Stable (MSS) Colorectal Cancer

A Phase II Study of Cabozantinib and Nivolumab in Refractory Metastatic Microsatellite Stable (MSS) Colorectal Cancer

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 48 (actual)
• Sponsor: University of Colorado, Denver · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Data from a prior phase II study of single agent cabozantinib in metastatic, refractory colorectal cancer (NCT03542877) combined with the compelling preclinical data in colorectal mouse models utilizing cabozantinib combined with nivolumab have led to this concept for a clinical trial to combine cabozantinib and nivolumab in patients with metastatic MSS CRC in the third line setting and beyond.

Detailed description

This is an open-label, single-arm, 2-stage, phase II study of cabozantinib in combination with nivolumab in patients with refractory metastatic CRC. Up to 46 evaluable patients will be treated with cabozantinib 40 mg orally daily in combination with nivolumab 480 mg IV every 28 days. One cycle is defined as 28 days.

Conditions

• Colorectal Adenocarcinoma
• Colon Cancer
• Colon Adenocarcinoma
• Rectum Cancer
• Rectal Cancer
• Rectal Adenocarcinoma
• Colorectal Cancer

Interventions

Type	Name	Description
DRUG	Cabozantinib	Cabozantinib is a multi-targeted inhibitor of RTKs. The targets of cabozantinib include several RTKs known to play important roles in tumor cell proliferation and/or tumor neovascularization, namely MET, VEGFR2 (also known as KDR), AXL, and RET. Other recognized targets of cabozantinib include ROS1, TRKA, TRKB, TIE2, TYRO3, and MER, two additional members of the VEGFR family (VEGFR1, VEGFR3), and the closely related RTKs KIT and FLT-3. The mode of action for cabozantinib is similar to other drugs targeting RTKs: binding in a fully reversible manner to a region of the kinase domain (including the ATP-binding site) which forces the kinase activation loop into a pseudo-inactive conformation, thereby inhibiting subsequent catalytic activity.
DRUG	Nivolumab	Nivolumab is a human monoclonal antibody that targets the programmed death-1 (PD-1) cluster of differentiation 279 (CD279) cell surface membrane receptor. Nivolumab binds specifically to the human PD-1 receptor and inhibits the interaction of PD-1 with its ligands, programmed death ligands-1 (PD-L1) and 2 (PD-L2), which promotes immune responses and antigen-specific T-cell responses to foreign- and self- antigens. Nivolumab is expressed in Chinese hamster ovary (CHO) cells and is produced using standard mammalian cell cultivation and chromatographic purification technologies.

Timeline

• Start date: 2021-06-23
• Primary completion: 2026-02-24
• Completion: 2027-02-09
• First posted: 2021-07-15
• Last updated: 2026-03-31

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study