Praluzatamab ravtansine, a CD166-targeting antibody-drug conjugate, in patients with advanced solid tumors: an open-label phase 1/2 trial.
Document Type
Article
Publication Date
2-14-2022
Publication Title
Clinical cancer research : an official journal of the American Association for Cancer Research
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
Department
Earle A. Chiles Research Institute
Department
Oncology
Department
Pharmacy
Recommended Citation
Boni, Valentina; Fidler, Mary J; Arkenau, Hendrik-Tobias; Spira, Alexander; Meric-Bernstam, Funda; Uboha, Nataliya; Sanborn, Rachel E; Sweis, Randy F; LoRusso, Patricia; Nagasaka, Misako; Garcia-Corbacho, Javier; Jalal, Shadia; Harding, James J; Kim, Stella K; Miedema, Iris H C; Vugts, Danielle J; Huisman, Marc C; Zwezerijnen, Gerben J C; van Dongen, Guus A M S; Menke-van der Houven van Oordt, Catharina W; Wang, Song; Dang, Tam; Zein, Ivan A; Vasiljeva, Olga; Lyman, Susan K; Paton, Virginia; Hannah, Alison; and Liu, Joyce F, "Praluzatamab ravtansine, a CD166-targeting antibody-drug conjugate, in patients with advanced solid tumors: an open-label phase 1/2 trial." (2022). Articles, Abstracts, and Reports. 5862.
https://digitalcommons.providence.org/publications/5862
