A Window of Opportunity Study of KTN3379 in Surgically Resectable Head and Neck Cancer Patients

The purpose of this study is to evaluate the activity and safety of KTN3379 in head and neck cancer patients and to explore downstream molecular pathways to identify tumor response and resistance mechanisms by evaluating various biomarkers before and after treatment.

Study Overview

• Status: Completed
• Conditions: Squamous Cell Carcinoma of the Head and Neck
• Intervention / Treatment: Biological: KTN3379

Detailed Description

This is an open-label study in patients with squamous cell carcinoma of the head and neck (SCCHN) scheduled for surgery. Two cohorts of SCCHN patients, HPV negative and HPV positive, will be treated with KTN3379 to evaluate effects on ErbB3 phosphorylation and other biomarkers in tumor tissue. The KTN3379 treatment duration is within the expected window of time that elapses from initial patient evaluation by a surgeon to performance of surgery. Paired preoperative and postoperative tumor specimen analyses allow evaluation of proliferation, ErbB3 related biomarkers, pErbB3 modulation and pharmacodynamic changes in downstream molecular pathways.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • UCSF Helen Diller Family Comprehensive Cancer Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed primary, untreated SCCHN including variants. Patients must be candidates for surgical resection. Primary tumors of oral cavity, oropharynx, hypopharnyx or larynx are included.
2. Written informed consent and any locally required authorization (e.g., HIPAA in the USA) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
3. Females of childbearing potential who are sexually active with a nonsterilized male partner must use 2 methods of effective contraception from screening, and must agree to continue using such precautions for 60 days after the final dose of KTN3379. Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or those who are postmenopausal (defined as 12 months with no menses without an alternative medical cause)
4. Nonsterilized males who are sexually active with a female partner of child-bearing potential must, with their partner, use 2 acceptable methods of effective contraception from Day 1 through 60 days after receipt of the final dose of KTN3379.
5. Eastern Cooperative Oncology Group (ECOG) status of 0 or 1

6. Adequate bone and marrow function as defined below:

   • Hemoglobin ≥ 10 g/dL
   • Absolute neutrophil count ≥ 1500/mm3
   • Platelet count ≥ 100,000/mm3
   • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 ×ULN
   • Bilirubin ≤ 1.5 × ULN except for cases of documented or suspected Gilbert's disease, in which bilirubin must be ≤ 5 × ULN
   • Serum creatinine ≤ 1.5 g/dL
   • Normal PT or INR and aPTT

Exclusion Criteria:

1. Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment.
2. Immunosuppressive or systemic steroids medication within 7 days before the first dose of KTN3379 (inhaled and topical corticosteroids are permitted).
3. Another invasive malignancy within 2 years prior to enrollment except for localized prostate cancer, cervical carcinoma in situ, non-melanomatous carcinoma of the skin, or ductal carcinoma in situ of the breast that has/have been surgically cured
4. Major surgical procedure within 30 days prior to Day 1 or incomplete recovery from any prior surgery
5. Pregnancy or lactation
6. Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled or idiopathic hypotension, unstable angina pectoris, cardiac arrhythmia including atrial fibrillation, significant cardiac conduction abnormalities including prolongation of QTc interval or BBB, active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent
7. Patients with a left ventricular cardiac ejection fraction < 50% as assessed by an echocardiogram or MUGA scan
8. Patients with prior primary treatment for head and neck cancer (e.g. chemoradiation or radiation alone).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Treatment with KTN3379 in HPV positive head and neck cancer patients	Biological: KTN3379
Experimental: B; Treatment with KTN3379 in HPV negative head and neck cancer patients	Biological: KTN3379

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pErbB3 levels in tumor tissue	Reduction in pErbB3 levels	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with adverse events as a measure of safety and tolerability	Adverse events (AEs), serious adverse events (SAEs), laboratory evaluations, radiological assessments, vital signs, electrocardiograms (ECGs), and physical examinations.	6 weeks
Ki67 proliferative index in tumor tissue	Ki67 proliferative index in tumor tissue before and after treatment	4 weeks
Changes in tumor measurements (RECIST 1.1 measurements)	RECIST 1.1 measurements before and after treatment	4 weeks
Pharmacokinetics (Peak plasma concentrations of KTN3379 Trough plasma concentrations of KTN3379)	Peak plasma concentrations of KTN3379 Trough plasma concentrations of KTN3379	4 weeks
Anti drug antibodies	Measurement of anti KTN3379 antibodies in blood	6 weeks

Collaborators and Investigators

• Sponsor: Celldex Therapeutics

Publications and helpful links

General Publications

• Duvvuri U, George J, Kim S, Alvarado D, Neumeister VM, Chenna A, Gedrich R, Hawthorne T, LaVallee T, Grandis JR, Bauman JE. Molecular and Clinical Activity of CDX-3379, an Anti-ErbB3 Monoclonal Antibody, in Head and Neck Squamous Cell Carcinoma Patients. Clin Cancer Res. 2019 Oct 1;25(19):5752-5758. doi: 10.1158/1078-0432.CCR-18-3453. Epub 2019 Jul 15.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): September 22, 2016
• Study Completion (Actual): October 10, 2016

Study Registration Dates

• First Submitted: June 11, 2015
• First Submitted That Met QC Criteria: June 16, 2015
• First Posted (Estimate): June 17, 2015

Study Record Updates

• Last Update Posted (Actual): August 1, 2019
• Last Update Submitted That Met QC Criteria: July 30, 2019
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: CDX3379
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: KTN3379-CL-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No