Phase II Trial of CDX-3379 and Cetuximab in Recurrent/Metastatic, HPV-Negative, Cetuximab-Resistant Head and Neck Cancer

Julie E. Bauman, Division of Hematology/Oncology, Department of Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA.
Ricklie Julian, Division of Hematology/Oncology, Department of Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA.
Nabil F. Saba, Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
Trisha M. Wise-Draper, Division of Hematology/Oncology, Department of Medicine, University of Cincinnati Cancer Center, University of Cincinnati, Cincinnati, OH 45267, USA.
Douglas R. Adkins, Division of Hematology/Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
Paul O'Brien, Division of Hematology/Oncology, Department of Medicine, MUSC Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
Mary Jo Fidler, Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, USA.
Michael K. Gibson, Division of Hematology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Umamaheswar Duvvuri, Division of Head and Neck Surgery, Department of Otolaryngology, UPMC Hillman Cancer Center, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15232, USA.
Margo Heath-Chiozzi, Celldex Therapeutics, Hampton, NJ 08827, USA.
Diego Alvarado, Celldex Therapeutics, Hampton, NJ 08827, USA.
Richard Gedrich, Celldex Therapeutics, Hampton, NJ 08827, USA.
Philip Golden, Celldex Therapeutics, Hampton, NJ 08827, USA.
Roger B. Cohen, Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Document Type

Journal Article

Publication Date

5-10-2022

Journal

Cancers

Volume

14

Issue

10

DOI

10.3390/cancers14102355

Keywords

CDX-3379; EGFR; ErbB3; cetuximab; head and neck cancer

Abstract

In phase I development, CDX-3379, an anti-ErbB3 monoclonal antibody, showed promising molecular and antitumor activity in head and neck squamous cell carcinoma (HNSCC), alone or in combination with cetuximab. Preliminary biomarker data raised the hypothesis of enhanced response in tumors harboring mutations. This phase II, multicenter trial used a Simon 2-stage design to investigate the efficacy of CDX-3379 and cetuximab in 30 patients with recurrent/metastatic, HPV-negative, cetuximab-resistant HNSCC. The primary endpoint was objective response rate (ORR). Secondary endpoints included ORR in patients with somatic mutations, progression-free survival (PFS), overall survival (OS), and safety. Thirty patients were enrolled from March 2018 to September 2020. The ORR in genomically unselected patients was 2/30 (6.7%; 95% confidence interval [CI], 0.8-22.1). Median PFS and OS were 2.2 (95% CI: 1.3-3.6) and 6.6 months (95% CI: 2.7-7.5), respectively. Tissue was available in 27 patients including one of two responders. ORR was 1/10 (complete response; 10%; 95% CI 0.30-44.5) in the -mutated versus 0/17 (0%; 95% CI: 0-19.5) in the -wildtype cohorts. Sixteen patients (53%) experienced treatment-related adverse events (AEs) ≥ grade 3. The most common AEs were diarrhea (83%) and acneiform dermatitis (53%). Dose modification was required in 21 patients (70%). The modest ORR coupled with excessive, dose-limiting toxicity of this combination precludes further clinical development. Dual ErbB3-EGFR inhibition remains of scientific interest in HPV-negative HNSCC. Should more tolerable combinations be identified, development in an earlier line of therapy and prospective evaluation of the hypothesis warrant consideration.

Department

Medicine

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