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

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.

• Authors: Richard D Kim, Nilofer S Azad, Michael A Morse, Elizabeth Poplin, Amit Mahipal, Benjamin Tan Jr, Sharon A Mavroukakis, Massimo Fantini, Kwong Y Tsang, Anjum Zaki, Jose Torrealba, Philip M Arlen, Muhammad S Beg
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 26 Issue 14 Pg. 3557-3564 (07 15 2020) ISSN: 1557-3265 [Electronic] United States
• PMID: 32303539 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2020 American Association for Cancer Research.

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents, Immunological
• MUC5AC protein, human
• Mucin 5AC
• ensituximab

Topics

• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antineoplastic Agents, Immunological (administration & dosage, adverse effects)
• Colorectal Neoplasms (diagnosis, drug therapy, immunology, mortality)
• Female
• Humans
• Infusions, Intravenous
• Male
• Middle Aged
• Mucin 5AC (antagonists & inhibitors, immunology)
• Neoplasm Staging
• Progression-Free Survival