PMID- 35625959
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 14
IP  - 10
DP  - 2022 May 10
TI  - Phase II Trial of CDX-3379 and Cetuximab in Recurrent/Metastatic, HPV-Negative, 
      Cetuximab-Resistant Head and Neck Cancer.
LID - 10.3390/cancers14102355 [doi]
LID - 2355
AB  - 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 FAT1 
      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 FAT1 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 FAT1-mutated versus 0/17 (0%; 95% CI: 0-19.5) in the 
      FAT1-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 FAT1 hypothesis warrant consideration.
FAU - Bauman, Julie E
AU  - Bauman JE
AUID- ORCID: 0000-0002-1398-6636
AD  - Division of Hematology/Oncology, Department of Medicine, University of Arizona 
      Cancer Center, University of Arizona, Tucson, AZ 85724, USA.
AD  - Division of Hematology/Oncology, Department of Medicine, GW Cancer Center, The 
      George Washington University, Washington, DC 20052, USA.
FAU - Julian, Ricklie
AU  - Julian R
AD  - Division of Hematology/Oncology, Department of Medicine, University of Arizona 
      Cancer Center, University of Arizona, Tucson, AZ 85724, USA.
FAU - Saba, Nabil F
AU  - Saba NF
AUID- ORCID: 0000-0003-4972-1477
AD  - Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory 
      University, Atlanta, GA 30322, USA.
FAU - Wise-Draper, Trisha M
AU  - Wise-Draper TM
AD  - Division of Hematology/Oncology, Department of Medicine, University of Cincinnati 
      Cancer Center, University of Cincinnati, Cincinnati, OH 45267, USA.
FAU - Adkins, Douglas R
AU  - Adkins DR
AD  - Division of Hematology/Oncology, Department of Medicine, Siteman Cancer Center, 
      Washington University School of Medicine, St. Louis, MO 63110, USA.
FAU - O'Brien, Paul
AU  - O'Brien P
AD  - Division of Hematology/Oncology, Department of Medicine, MUSC Hollings Cancer 
      Center, Medical University of South Carolina, Charleston, SC 29425, USA.
FAU - Fidler, Mary Jo
AU  - Fidler MJ
AD  - Department of Internal Medicine, Rush University Medical Center, Chicago, IL 
      60612, USA.
FAU - Gibson, Michael K
AU  - Gibson MK
AD  - Division of Hematology, Department of Medicine, Vanderbilt-Ingram Cancer Center, 
      Vanderbilt University Medical Center, Nashville, TN 37232, USA.
FAU - Duvvuri, Umamaheswar
AU  - Duvvuri U
AD  - Division of Head and Neck Surgery, Department of Otolaryngology, UPMC Hillman 
      Cancer Center, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 
      15232, USA.
FAU - Heath-Chiozzi, Margo
AU  - Heath-Chiozzi M
AD  - Celldex Therapeutics, Hampton, NJ 08827, USA.
FAU - Alvarado, Diego
AU  - Alvarado D
AD  - Celldex Therapeutics, Hampton, NJ 08827, USA.
FAU - Gedrich, Richard
AU  - Gedrich R
AD  - Celldex Therapeutics, Hampton, NJ 08827, USA.
FAU - Golden, Philip
AU  - Golden P
AD  - Celldex Therapeutics, Hampton, NJ 08827, USA.
FAU - Cohen, Roger B
AU  - Cohen RB
AD  - Division of Hematology/Oncology, Department of Medicine, Perelman School of 
      Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
LA  - eng
PT  - Journal Article
DEP - 20220510
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC9139981
OTO - NOTNLM
OT  - CDX-3379
OT  - EGFR
OT  - ErbB3
OT  - cetuximab
OT  - head and neck cancer
COIS- M.H.-C., D.A., R.G. and P.G. are employed by Celldex Therapeutics. The remaining 
      authors declare no potential conflict of interest.
EDAT- 2022/05/29 06:00
MHDA- 2022/05/29 06:01
PMCR- 2022/05/10
CRDT- 2022/05/28 01:08
PHST- 2022/03/17 00:00 [received]
PHST- 2022/05/03 00:00 [revised]
PHST- 2022/05/03 00:00 [accepted]
PHST- 2022/05/28 01:08 [entrez]
PHST- 2022/05/29 06:00 [pubmed]
PHST- 2022/05/29 06:01 [medline]
PHST- 2022/05/10 00:00 [pmc-release]
AID - cancers14102355 [pii]
AID - cancers-14-02355 [pii]
AID - 10.3390/cancers14102355 [doi]
PST - epublish
SO  - Cancers (Basel). 2022 May 10;14(10):2355. doi: 10.3390/cancers14102355.