Phase II Study of Ensituximab, a Novel Chimeric Monoclonal Antibody, in Adults with Unresectable, Metastatic Colorectal Cancer

  • Clin Cancer Res. 2020 Jul 15;26(14):3557-3564. doi: 10.1158/1078-0432.CCR-20-0426.
Richard D Kim  1 ,  Nilofer S Azad  2 ,  Michael A Morse  3 ,  Elizabeth Poplin  4 ,  Amit Mahipal  5 ,  Benjamin Tan Jr  6 ,  Sharon A Mavroukakis  7 ,  Massimo Fantini  7 ,  Kwong Y Tsang  7 ,  Anjum Zaki  7 ,  Jose Torrealba  8 ,  Philip M Arlen  7 ,  Muhammad S Beg  9
Affiliations
  • 1. Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida. [email protected].
  • 2. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • 3. Department of Oncology, Duke University Medical Center, Durham, North Carolina.
  • 4. Department of Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
  • 5. Department of Oncology, Mayo Clinic, Rochester, Minnesota.
  • 6. Department of Oncology, Washington University School of Medicine Siteman Cancer Center, St. Louis, Missouri.
  • 7. Precision Biologics, Inc., Bethesda, Maryland.
  • 8. Department of Pathology, University of Texas Southwestern Medical Center of Dallas, Dallas, Texas.
  • 9. Department of Oncology, University of Texas Southwestern Medical Center of Dallas, Dallas, Texas.
PMID: 32303539 DOI: 10.1158/1078-0432.CCR-20-0426
Abstract

Purpose: Patients with metastatic colorectal Cancer refractory to chemotherapy have limited treatment options. Ensituximab (NEO-102) is a novel chimeric mAb targeting a variant of MUC5AC with specificity to colorectal Cancer.

Patients and methods: Single-arm, phase II trial assessed the efficacy and safety of ensituximab in patients with advanced, refractory Cancer who expressed MUC5AC antigen in tumor tissue. Ensituximab was administered intravenously every 2 weeks with 3 mg/kg as recommended phase II dose (RP2D). A minimum sample size of 43 patients was required on the basis of the assumption that ensituximab would improve median overall survival (OS) by 7 months using a one-sided significance level of 10% and 80% power. Written informed consent was obtained from all patients.

Results: Sixty-three patients with advanced, refractory colorectal Cancer were enrolled and 53 subjects were treated in phase II arm. Median age was 58 years and 46% of the patients were female. Among 57 evaluable patients, median OS was 6.8 months. No responses were observed, and stable disease was achieved in 21% of the patients. The most common treatment-related adverse events (AE) at RP2D included fatigue (38%), anemia (30%), nausea (15%), vomiting (11%), increased bilirubin (9%), constipation (8%), decreased appetite (6%), and diarrhea (6%). Serious AEs at least possibly related to ensituximab occurred in 4 patients and included anemia, nausea, increased bilirubin, and hypoxia. No patients discontinued treatment due to drug-related AEs.

Conclusions: Ensituximab was well tolerated and demonstrated modest antitumor activity in patients with heavily pretreated refractory colorectal Cancer.

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