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

  • Clin Cancer Res. 2022 May 13;28(10):2020-2029. doi: 10.1158/1078-0432.CCR-21-3656.
Valentina Boni  1 ,  Mary J Fidler  2 ,  Hendrik-Tobias Arkenau  3 ,  Alexander Spira  4 ,  Funda Meric-Bernstam  5 ,  Nataliya Uboha  6 ,  Rachel E Sanborn  7 ,  Randy F Sweis  8 ,  Patricia LoRusso  9 ,  Misako Nagasaka  10 ,  Javier Garcia-Corbacho  11 ,  Shadia Jalal  12 ,  James J Harding  13 ,  Stella K Kim  14 ,  Iris H C Miedema  15 ,  Danielle J Vugts  16 ,  Marc C Huisman  16 ,  Gerben J C Zwezerijnen  16 ,  Guus A M S van Dongen  16 ,  C Willemien Menke van der Houven van Oordt  15 ,  Song Wang  17 ,  Tam Dang  17 ,  Ivan A Zein  17 ,  Olga Vasiljeva  17 ,  Susan K Lyman  17 ,  Virginia Paton  17 ,  Alison Hannah  17 ,  Joyce F Liu  18
Affiliations
  • 1. START Madrid HM CIOCC (Centro Integral Oncológico Clara Campal), Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain.
  • 2. Rush University Medical Center, Chicago, Illinois.
  • 3. Sarah Cannon Research Institute UK Limited, London, United Kingdom.
  • 4. Virginia Cancer Specialists, Fairfax, Virginia.
  • 5. MD Anderson Cancer Center, Houston, Texas.
  • 6. University of Wisconsin-Carbone Cancer Center, Madison, Wisconsin.
  • 7. Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, Oregon.
  • 8. University of Chicago Medicine, Chicago, Illinois.
  • 9. Yale University School of Medicine, New Haven, Connecticut.
  • 10. Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
  • 11. Hospital Clinic Barcelona, Barcelona/IDIBAPs, Spain.
  • 12. Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana.
  • 13. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York.
  • 14. Robert Cizik Eye Clinic, Houston, Texas.
  • 15. Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands.
  • 16. Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands.
  • 17. CytomX Therapeutics, Inc., South San Francisco, California.
  • 18. Dana-Farber Cancer Institute, Boston, Massachusetts.
PMID: 35165101 DOI: 10.1158/1078-0432.CCR-21-3656
Abstract

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 = 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 = 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 conjugate to CD166 to demonstrate both translational and clinical activity in a variety of tumor types.

Products