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Clinical Trial 20144
Cancer Type: Head & Neck
Interventions:CUE-101 ()
Study Type: Treatment
Phase of Study: Phase I
Investigators:
- Christine Chung
Call 813-745-6100 or 1-800-679-0775
Overview
Study Title
A Phase 1, First-in-Human, Open-Label, Dose Escalation and Expansion Study of CUE-101 Monotherapy in Patients with HPV+ Recurrent / Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
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 in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).
Objective
Part A: Dose escalation and expansion of CUE-101 as monotherapy Part B: Dose confirmation Co-primary objectives: > To assess the safety and tolerability of CUE-101 in subjects with recurrent/metastatic HPV16-driven malignancies (HLA-A*0201, HPV16+ disease: HPV 16 genotyping, plus tumor p16+) and to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) based on markers of biological activity (biologically effective dose) (Part A) > To evaluate the pharmacokinetics (PK) of CUE-101 when administered in subjects with recurrent/metastatic HPV16-driven malignancies (Parts A and B) Secondary objectives: > To confirm safety and evaluate antitumor activity at the RP2D (Part B) > To assess the preliminary antitumor activity of CUE-101 based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Parts A and B) > To assess the potential for immune response upon treatment with CUE-101 (Parts A and B) > To assess the potential immunogenicity of CUE-101 (Parts A and B)
Inclusion Criteria
Ability to provide informed consent and documentation of informed consent prior to initiation of any study-related tests or procedures that are not part of standard of care for the Participant's disease. Participants must also be willing and able to comply with study procedures, including the acquisition of specified research specimens. Age >18 years old Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Life expectancy > 12 weeks Measurable disease as per RECIST 1.1 and documented by computed tomography (CT) and/or magnetic resonance imaging (MRI). Cutaneous or subcutaneous lesions must be measurable by calipers. Note: Lesions to be used as measurable disease for the purpose of response assessment must either a) not reside in a field that has been subjected to prior radiotherapy, or b) have demonstrated clear evidence of radiographic progression since the completion of prior radiotherapy and prior to study enrollment. Recurrent and metastatic HNSCC that has progressed following at least 1 prior systemic therapy. Participants must have received platinum-based chemotherapy and been offered checkpoint immunotherapy. The requirement for prior systemic therapy may be waived if a Participant was intolerant of or refused standard first or second-line therapies. Participant must have HLA-A*0201 genotype as determined by genomic testing performed at a central laboratory determined by the Sponsor prior to enrollment. Participant must have histologically and/or cytologically proven tumor(s) that are HPV16 positive and express 16INK4A. Archival tissue or formalin-fixed, paraffin-embedded (FFPE) tissue from a biopsy and / or surgery must be available for HPV16 and p16INK4A testing on all Participants enrolled. All tumors must test positive for HPV16 using ISH analysis and p16INK4A expression in tumor cells using IHC analysis performed at a central laboratory determined by the Sponsor prior to enrollment. All tumors must have histologically or cytologically confirmed diagnoses. Laboratory Features Acceptable laboratory parameters as per protocol Reproductive Features Female Participants of childbearing potential (not surgically sterilized and between menarche and 1 year post-menopause) must have a negative serum pregnancy test performed within 72 hours prior to the initiation of study drug administration. Further, female Participants of childbearing potential must agree to use acceptable contraceptive measures from the time of consent through 30 days after discontinuation of study drug administration. For female Participants, 2 forms of contraception must be utilized and may include oral, transdermal, injectable or implantable contraceptives, intrauterine device, female condom, diaphragm with spermicide, cervical cap, use of a condom by the sexual partner or a sterile or vasectomized sexual partner. Periodic abstinence (eg, calendar, ovulation, symptothermal, and post ovulation methods) and withdrawal are not considered acceptable forms of contraception in this study. Non-vasectomized male Participants with partners of childbearing potential must use barrier contraception. In addition, male Participants should also have their partners use another method of contraception from the time of consent through 30 days after discontinuation of study drug administration Female Participants should not be pregnant or plan to become pregnant during the course of the trial. Female Participants must not be breastfeeding. Previous Checkpoint Inhibitor Therapy Participants who have previously received an immune checkpoint inhibitor (eg, anti-PD-L1, anti-PD-1, anti-CTLA-4) prior to enrollment must have toxicities related to the checkpoint inhibitor resolved to < Grade 1 or baseline (prior to the checkpoint inhibitor) to be eligible for enrollment.
Exclusion Criteria
Participants with symptomatic central nervous system (CNS) metastases must have been treated and be asymptomatic Need for concurrent treatment for the CNS disease (eg, surgery, radiation, corticosteroids > 10 mg prednisone / day or equivalent) Progression of CNS metastases on MRI or CT for at least 28 days after last day of prior therapy for the CNS metastases; and/or Concurrent leptomeningeal disease or cord compression. Participants with any history of known or suspected autoimmune disease with the specific exceptions of the following: Vitiligo, Resolved childhood atopic dermatitis, Psoriasis (with exception of psoriatic arthritis) not requiring systemic treatment (within the past 2 years), Participants with a history of Grave's disease that are now euthyroid clinically and by laboratory testing History of prior allogeneic bone marrow, stem-cell or solid organ transplantation. Treatment with any systemic anti-neoplastic therapy, or investigational therapy within the 2 weeks prior to the initiation of study drug administration. Participants may be on an investigational or other anti-neoplastic therapy during the screening phase of the study. Treatment with radiation therapy within 2 weeks prior to the initiation of study drug administration. Treatment with corticosteroids (>10 mg per day prednisone or equivalent) or other immune suppressive drugs within the 14 days prior to the initiation of study drug administration. Steroids for topical, ophthalmic, inhaled, or nasal administration are allowed. Physiological replacement with hydrocortisone up to a maximum dose of 40 mg per day is allowed. History of clinically significant cardiovascular disease including, but not limited to: Myocardial infarction or unstable angina within the 16 weeks prior to the initiation of study drug Clinically significant cardiac arrhythmias Uncontrolled hypertension: systolic blood pressure (BP) >180 mmHg, diastolic BP >100 mmHg Deep vein thrombosis, pulmonary embolism, stroke, or transient ischemic attack within the 16 weeks prior to the initiation of study drug QTcB prolongation > 480 msec Congestive heart failure Pericarditis/clinically significant pericardial effusion Myocarditis Clinically significant pulmonary compromise (eg, requirement for supplemental oxygen) Clinically significant GI disorders including: History of GI perforation within 1 year prior to study drug administration. Participants with a history of GI perforation that occurred more than 1 year ago can only be enrolled if the Investigator no longer considers the previously affected area to be at risk for perforation; History of clinically significant GI bleeding within 3 months prior to the initiation of study drug; History of acute pancreatitis within 3 months prior to the initiation of study drug; and/or Diverticulitis that is clinically significant in the opinion of the Investigator based on the extent or severity of known disease and/or the occurrence of clinically significant disease flares within 4 weeks prior to the initiation of study drug administration. Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days prior to the initiation of study drug. Participants requiring any systemic antiviral, antifungal, or antibacterial therapy for active infection must have completed treatment no less than 1 week prior to the initiation of study drug Positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome Known history of hepatitis B or hepatitis C infection or known positive test for hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C polymerase chain reaction Second primary invasive malignancy that has not been in remission for greater than 2 years
