Praluzatamab Ravtansine, a CD166-Targeting Antibody- Drug Conjugate, in Patients with Advanced Solid Tumors: An Open-Label Phase I/II Trial: An Open-Label Phase I/II Trial

Valentina Boni, Mary J. Fidler, Hendrik-Tobias Arkenau, Alexander Spira, Funda Meric-Bernstam, Nataliya Uboha, Rachel E. Sanborn, Randy F. Sweis, Patricia LoRusso, Misako Nagasaka, Javier Garcia-Corbacho, Shadia Jalal, James J. Harding, Stella K. Kim, Iris H. C. Miedema, Danielle J. Vugts, Marc C. Huisman, Gerben J. C. Zwezerijnen, Guus A. M. S. van Dongen, C. Willemien Menke van der Houven van OordtSong Wang, Tam Dang, Ivan A. Zein, Olga Vasiljeva, Susan K. Lyman, Virginia Paton, Alison Hannah, Joyce F. Liu

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)


Purpose: Praluzatamab ravtansine (CX-2009) is a conditionally activated Probody drug conjugate (PDC) comprising an anti-CD166 mAb conjugated to DM4, with a protease-cleavable linker and a peptide mask that limits target engagement in normal tissue and circulation. The tumor microenvironment is enriched for proteases capable of cleaving the linker, thereby releasing the mask, allowing for localized binding of CX-2009 to CD166. CX-2009 was evaluated in a phase I/II clinical trial for patients with advanced solid tumors. Patients and Methods: Eligible patients had metastatic cancer receiving ≥2 prior treatments. CX-2009 was administered at escalating doses every 3 weeks (0.25–10 mg/kg) or every 2 weeks (4–6 mg/kg). Primary objective was to determine the safety profile and recommended phase II dose (RP2D). Results: Of 99 patients enrolled, the most prevalent subtype was breast cancer (n ¼ 45). Median number of prior therapies was 5 (range, 1–19). Dose-limiting toxicities were observed at 8 mg/kg every 3 weeks and 6 mg/kg every 2 weeks. On the basis of tolerability, the RP2D was 7 mg/kg every 3 weeks. Tumor regressions were observed at doses ≥4 mg/kg. In the hormone receptor–positive/HER2-nonamplified breast cancer subset (n ¼ 22), 2 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 of 22 posttreatment biopsies. Conclusions: CD166 is a novel, ubiquitously expressed target. CX-2009 is the first conditionally activated antibody–drug conjugatetoCD166todemonstratebothtranslationalandclinicalactivity in a variety of tumor types.

Original languageEnglish
Pages (from-to)2020-2029
Number of pages10
JournalClinical cancer research : an official journal of the American Association for Cancer Research
Issue number10
Early online date14 Feb 2022
Publication statusPublished - 15 May 2022

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