A Phase 1 Study in Patients With HPV16+ Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma

Phase 1

Active, not recruiting

Conditions: Head and Neck Cancer
HPV Positive Oropharyngeal Squamous Cell Carcinoma
HPV-Related Carcinoma

Brief Summary: This is a multi-center, open-label, phase 1 dose escalation and expansion study evaluating the safety, anti-tumor effect, and immunogenicity of CUE-101 as monotherapy treatment in second line or CUE-101 Combination Therapy with Pembrolizumab in first line patients with HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)

Detailed Description: CUE-101 is a novel fusion protein designed to activate and expand a population of tumor specific T cells to eradicate human papilloma virus (HPV)-driven malignancies. HPV causes multiple tumor types including cervical, head and neck squamous cell carcinoma (HNSCC) and anal cancers. Initial testing of CUE-101 will be conducted in HPV16+ HNSCC patients.

The primary objectives of the Part A\&B, first-in-human trial, are to assess the safety and tolerability of CUE-101 in subjects with recurrent/metastatic HNSCC in the second line setting and to determine the maximum tolerated dose or recommended Phase 2 dose based on markers of biological activity. Pharmacokinetics (PK), antitumor immune response, preliminary antitumor activity and the potential for immunogenicity will also be assessed. The goal of Part C\&D is to characterize the safety, tolerability, and biological effects of CUE-101 in combination with pembrolizumab in patients with recurrent/metastatic HNSCC in the first line setting. This will be an open-label multicenter phase I trial conducted in the U.S. involving approximately 85 patients.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
CUE-101 dose escalation and expansion	CUE-101	Part A\&B: CUE-101 Monotherapy IV infusion Q3W Dose Escalation (Part A) and Expansion (Part B)
Pembrolizumab and CUE-101	CUE-101	Part C\&D: CUE-101 Dose Escalation in Combination with KEYTRUDA® (pembrolizumab) for injection, for IV use 200 mg Q3W (Part C). Expansion of pembrolizumab plus CUE-101 at the combination RP2D (Part D)
Pembrolizumab and CUE-101	KEYTRUDA®, Pembrolizumab	Part C\&D: CUE-101 Dose Escalation in Combination with KEYTRUDA® (pembrolizumab) for injection, for IV use 200 mg Q3W (Part C). Expansion of pembrolizumab plus CUE-101 at the combination RP2D (Part D)

Primary Outcome Measures

Name	Time	Method
Dose Limiting Toxicity	36 months	The number of subjects who have dose limiting toxicities (DLTs), defined as clinically significant or ≥ Grade 3 Common Terminology Criteria for Adverse Events (CTCAE) v5.0, changes in adverse events (AEs), safety laboratory tests, physical examinations, electrocardiograms (ECGs), or vital signs
Serum PK parameters for CUE-101	36 months	Terminal half-life of CUE-101

Secondary Outcome Measures

Name	Time	Method
Overall response rate (ORR)	36 months	For ORR: Complete and partial responses as well as stable disease parameters will be followed

Locations (17): University of Washington School of Medicine
🇺🇸
Seattle, Washington, United States
Gabrail Cancer Center
🇺🇸
Canton, Ohio, United States
Affiliated Oncologists, LLC
🇺🇸
Chicago, Illinois, United States
Barbara Karmanos Cancer Center/ Wayne State University School of Medicine
🇺🇸
Detroit, Michigan, United States
George Washington University Cancer Center
🇺🇸
Washington, District of Columbia, United States
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
University of Arizona
🇺🇸
Tucson, Arizona, United States
Emory University School of Medicine
🇺🇸
Atlanta, Georgia, United States
University of Texas MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Moffitt Cancer Center
🇺🇸
Tampa, Florida, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Yale School of Medicine
🇺🇸
New Haven, Connecticut, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
🇺🇸
Baltimore, Maryland, United States
Vanderbilt-Ingram Cancer Center (VICC)
🇺🇸
Nashville, Tennessee, United States
Washington University
🇺🇸
Saint Louis, Missouri, United States
Stanford University Medical Center
🇺🇸
Palo Alto, California, United States