Dataset Information

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

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.

SUBMITTER: Boni V

PROVIDER: S-EPMC9365353 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

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

Boni Valentina V Fidler Mary J MJ Arkenau Hendrik-Tobias HT Spira Alexander A Meric-Bernstam Funda F Uboha Nataliya N Sanborn Rachel E RE Sweis Randy F RF LoRusso Patricia P Nagasaka Misako M Garcia-Corbacho Javier J Jalal Shadia S Harding James J JJ Kim Stella K SK Miedema Iris H C IHC Vugts Danielle J DJ Huisman Marc C MC Zwezerijnen Gerben J C GJC van Dongen Guus A M S GAMS Menke van der Houven van Oordt C Willemien CW Wang Song S Dang Tam T Zein Ivan A IA Vasiljeva Olga O Lyman Susan K SK Paton Virginia V Hannah Alison A Liu Joyce F JF

Clinical cancer research : an official journal of the American Association for Cancer Research 20220501 10

<h4>Purpose</h4>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 patien ...[more]

PMID: 35165101

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Dataset Information

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

Purpose

Patients and methods

Results

Conclusions

Publications

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

Similar Datasets

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