Praluzatamab ravtansine, a CD166-targeting antibody-drug conjugate, in patients with advanced solid tumors: an open-label phase 1/2 trial.
Publication Title
Clinical cancer research : an official journal of the American Association for Cancer Research
Document Type
Article
Publication Date
2-14-2022
Keywords
oregon; chiles; portland
Abstract
PURPOSE: Praluzatamab ravtansine (CX-2009) is a conditionally activated Probody
EXPERIMENTAL DESIGN: Eligible patients had metastatic cancer receiving {greater than or equal to}2 prior treatments. CX-2009 was administered at escalating doses every 3 weeks (0.25-10 mg/kg; Q3W) or every 2 weeks (4-6 mg/kg; Q2W). Primary objective was to determine the safety profile and recommended phase 2 dose (RP2D).
RESULTS: Of 99 patients enrolled, the most prevalent subtype was breast cancer (BC) (n=45). Median number of prior therapies was 5 (range, 1-19). Dose-limiting toxicities were observed at 8 mg/kg Q3W and 6 mg/kg Q2W. Based on tolerability, the RP2D was 7 mg/kg Q3W. Tumor regressions were observed at doses {greater than or equal to}4 mg/kg. In the HR-positive/HER2-non-amplified BC subset (n=22), two patients (9%) had confirmed partial responses, and 10 patients (45%) had stable disease. Imaging with zirconium-labeled CX-2009 confirmed uptake in tumor lesions and shielding of major organs. Activated, unmasked CX-2009 was measurable in 18/22 post-treatment biopsies.
CONCLUSION: CD166 is a novel, ubiquitously expressed target. CX-2009 is the first conditionally activated antibody-drug conjugate to CD166 to demonstrate both translational and clinical activity in a variety of tumor types.
Clinical Institute
Cancer
Specialty/Research Institute
Earle A. Chiles Research Institute
Specialty/Research Institute
Oncology
Specialty/Research Institute
Pharmacy
