TY - JOUR
T1 - Praluzatamab Ravtansine, a CD166-Targeting Antibody–Drug Conjugate, in Patients with Advanced Solid Tumors
T2 - An Open-Label Phase I/II Trial
AU - Boni, Valentina
AU - Fidler, Mary J.
AU - Arkenau, Hendrik Tobias
AU - Spira, Alexander
AU - Meric-Bernstam, Funda
AU - Uboha, Nataliya
AU - Sanborn, Rachel E.
AU - Sweis, Randy F.
AU - LoRusso, Patricia
AU - Nagasaka, Misako
AU - Garcia-Corbacho, Javier
AU - Jalal, Shadia
AU - Harding, James J.
AU - Kim, Stella K.
AU - Miedema, Iris H.C.
AU - Vugts, Danielle J.
AU - Huisman, Marc C.
AU - Zwezerijnen, Gerben J.C.
AU - van Dongen, Guus A.M.S.
AU - van der Houven van Oordt, C. Willemien Menke
AU - Wang, Song
AU - Dang, Tam
AU - Zein, Ivan A.
AU - Vasiljeva, Olga
AU - Lyman, Susan K.
AU - Paton, Virginia
AU - Hannah, Alison
AU - Liu, Joyce F.
N1 - Publisher Copyright:
© 2022 The Authors; Published by the American Association for Cancer Research
PY - 2022/5/15
Y1 - 2022/5/15
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-21-3656
DO - 10.1158/1078-0432.CCR-21-3656
M3 - Article
C2 - 35165101
AN - SCOPUS:85130631607
SN - 1078-0432
VL - 28
SP - 2020
EP - 2029
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 10
ER -