Cabozantinib and Panitumumab to Treat KRAS Wild-Type Metastatic Colorectal Cancer

Summary

There will be three parts to this phase I study: 1) the Combination Dose Finding cohort; 2) the Combination Expansion cohort; and 3) the Monotherapy MET Amplified cohort. In the Combination Dose Finding cohort and the Combination Expansion cohort, we will combine cabozantinib and panitumumab in patients with KRAS wild-type metastatic colorectal cancer (CRC). In the Monotherapy MET Amplified cohort, we will screen at least 50 patients for MET gene amplification ("MET amplification"). Patients with MET amplification will receive cabozantinib only (monotherapy). The primary objective of this open-label phase Ib trial are: 1. To determine the maximum tolerated dose and the recommended phase II dose for the combination of cabozantinib and panitumumab in patients with KRAS wild-type metastatic colorectal cancer and 2. To identify the objective response rate (ORR) of cabozantinib monotherapy in patients with prospectively identified MET amplified metastatic colorectal cancer. The secondary objectives are: 1. To describe the non-dose limiting toxicities of cabozantinib and panitumumab. 2. To describe the clinical activity (ORR, PFS, OS) of cabozantinib and panitumumab. 3. To describe the safety and tolerability of cabozantinib monotherapy in patients with MET amplified colorectal cancer. 4. To describe the clinical activity (PFS, OS) of cabozantinib monotherapy in patients with MET amplified colorectal cancer.

Timeline

Start

2014-01

Primary completion

2018-05-10

Completion

2018-08-29

Publications

• Results Strickler JH, Rushing CN, Uronis HE, Morse MA, Niedzwiecki D, Blobe GC, Moyer AN, Bolch E, Webb R, Haley S, Hatch AJ, Altomare IP, Sherrill GB, Chang DZ, Wells JL, Hsu SD, Jia J, Zafar SY, Nixon AB, Hurwitz HI. Cabozantinib and Panitumumab for RAS Wild-Type Metastatic Colorectal Cancer. Oncologist. 2021 Jun;26(6):465-e917. doi: 10.1002/onco.13678. Epub 2021 Feb 9.
• Jia J, Howard L, Liu Y, Starr MD, Brady JC, Niedzwiecki D, Strickler JH, Nixon AB. Cabozantinib with or without Panitumumab for RAS wild-type metastatic colorectal cancer: impact of MET amplification on clinical outcomes and circulating biomarkers. Cancer Chemother Pharmacol. 2022 Mar;89(3):413-422. doi: 10.1007/s00280-022-04404-8. Epub 2022 Feb 16.

Drugs

Indications