Phase I, first-in-human study of the Probody therapeutic CX-2029 in adults with advanced solid tumor malignancies

Melissa Johnson, Anthony El-Khoueiry, Navid Hafez, Nehal Lakhani, Hirva Mamdani, Jordi Rodon, Rachel E. Sanborn, Javier Garcia-Corbacho, Valentina Boni, Mark Stroh, Alison L. Hannah, Song Wang, Henry Castro, Alexander Spira

Research output: Contribution to journalArticlepeer-review


Purpose: PROCLAIM-CX-2029 is a phase I first-in-human study of CX-2029, a Probody-drug conjugate targeting CD71 (transferrin receptor 1) in adults with advanced solid tumors. Although the transferrin receptor is highly expressed across multiple tumor types, it has not been considered a target for antibody-drug conjugates (ADCs) due to its broad expression on normal cells. CX-2029 is a masked form of a proprietary anti-CD71 antibody conjugated to monomethyl auristatin E, designed to be unmasked in the tumor microenvironment by tumor-associated proteases, therefore limiting off-tumor toxicity and creating a therapeutic window for this previously undruggable target. Patients and Methods: This was a dose-escalation, multicenter trial to evaluate the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of CX-2029. The primary endpoint was to determine the maximum tolerated dose (MTD) and cycle 1 dose-limiting toxicity (DLT). CX-2029 was administered i.v. every 3 weeks. Results: Forty-five patients were enrolled in eight dose levels. No DLTs were reported in the dose escalation through 4 mg/kg. At 5 mg/kg, there were two DLTs (febrile neutropenia and pancytopenia). Following expansion of the 4 mg/kg dose to six patients, two additional DLTs were observed (infusion-related reaction and neutropenia/anemia). Both the 4 and 5 mg/kg doses were declared above the maximum tolerated dose. The recommended phase II dose is 3 mg/kg. The most common dose-dependent hematologic toxicities were anemia and neutropenia. Confirmed partial responses were observed in three patients, all with squamous histologies. Conclusions: The Probody therapeutic platform enables targeting CD71, a previously undruggable ADC target, at tolerable doses associated with clinical activity.

Original languageEnglish (US)
Pages (from-to)4521-4530
Number of pages10
JournalClinical Cancer Research
Issue number16
StatePublished - Aug 15 2021
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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