First-in-human phase 1 clinical trial of anti-core 1 O-glycans targeting monoclonal antibody NEO-201 in treatment-refractory solid tumors

Christopher B. Cole, Maria Pia Morelli, Massimo Fantini*, Markku Miettinen, Patricia Fetsch, Cody Peer, William D. Figg, Tyler Yin, Nicole Houston, Ann McCoy, Stanley Lipkowitz, Alexandra Zimmer, Jung min Lee, Miroslava Pavelova, Erin N. Villanueva, Kathryn Trewhitt, B. Brooke Solarz, Maria Fergusson, Sharon A. Mavroukakis, Anjum ZakiKwong Y. Tsang, Philip M. Arlen, Christina M. Annunziata*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background: NEO201 is a humanized IgG1 monoclonal antibody (mAb) generated against tumor-associated antigens from patients with colorectal cancer. NEO-201 binds to core 1 or extended core 1 O-glycans expressed by its target cells. Here, we present outcomes from a phase I trial of NEO-201 in patients with advanced solid tumors that have not responded to standard treatments. Methods: This was a single site, open label 3 + 3 dose escalation clinical trial. NEO-201 was administered intravenously every two weeks in a 28-day cycle at dose level (DL) 1 (1 mg/kg), DL 1.5 (1.5 mg/kg) and DL 2 (2 mg/kg) until dose limiting toxicity (DLT), disease progression, or patient withdrawal. Disease evaluations were conducted after every 2 cycles. The primary objective was to assess the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of NEO-201. The secondary objective was to assess the antitumor activity by RECIST v1.1. The exploratory objectives assessed pharmacokinetics and the effect of NEO-201 administration on immunologic parameters and their impact on clinical response. Results: Seventeen patients (11 colorectal, 4 pancreatic and 2 breast cancers) were enrolled; 2 patients withdrew after the first dose and were not evaluable for DLT. Twelve of the 15 patients evaluable for safety discontinued due to disease progression and 3 patients discontinued due to DLT (grade 4 febrile neutropenia [1 patient] and prolonged neutropenia [1 patient] at DL 2, and grade 3 prolonged (> 72 h) febrile neutropenia [1 patient] at DL 1.5). A total of 69 doses of NEO-201 were administered (range 1–15, median 4). Common (> 10%) grade 3/4 toxicities occurred as follows: neutropenia (26/69 doses, 17/17 patients), white blood cell decrease (16/69 doses, 12/17 patients), lymphocyte decrease (8/69 doses, 6/17 patients). Thirteen patients were evaluable for disease response; the best response was stable disease (SD) in 4 patients with colorectal cancer. Analysis of soluble factors in serum revealed that a high level of soluble MICA at baseline was correlated with a downregulation of NK cell activation markers and progressive disease. Unexpectedly, flow cytometry showed that NEO-201 also binds to circulating regulatory T cells and reduction of the quantities of these cells was observed especially in patients with SD. Conclusions: NEO-201 was safe and well tolerated at the MTD of 1.5 mg/kg, with neutropenia being the most common adverse event. Furthermore, a reduction in the percentage of regulatory T cells following NEO-201 treatment supports our ongoing phase II clinical trial evaluating the efficiency of the combination of NEO-201 with the immune checkpoint inhibitor pembrolizumab in adults with treatment-resistant solid tumors. Trial registration: NCT03476681. Registered 03/26/2018. Graphical Abstract: [Figure not available: see fulltext.]

Original languageEnglish
Article number76
JournalJournal of Experimental and Clinical Cancer Research
Issue number1
StatePublished - Dec 2023
Externally publishedYes


  • Antibody-dependent cellular cytotoxicity
  • Cancer immunotherapy
  • Clinical trial
  • Monoclonal antibody
  • NEO-201
  • O-glycan
  • Regulatory T cells


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