A Phase 1, First-in-Human, Open-Label, Dose Escalation and Expansion Study of CUE-101 Monotherapy in Second Line and CUE-101 Combination Therapy with Pembrolizumab in First Line Patients with HPV16+ Recurrent / Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
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).
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)
CUE-101 (); Pembrolizumab (Keytruda)
- 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. Eligibility will be determined based on either local or central laboratory testing. If local results are used, then a duplicate sample must be submitted for confirmation at a central laboratory designated by the Sponsor.
- Participant must have histologically and/or cytologically proven tumor(s) that are HPV16 positive and express p6INK4A. 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. Eligibility will be based on either local or central HPV16 and p16INK4A testing. If local results are used then tissue must be submitted for confirmation in a central laboratory designated by the Sponsor.
- 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 120 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.
- Additional criteria apply
- 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 tissue/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
- 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
- History of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
- Known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
- Second primary invasive malignancy that has not been in remission for greater than 2 years
- Other criteria apply
If you are interested in learning more about clinical trials, our clinical trial navigators can discuss your options and recommend opportunities that may be suitable for you. Call 813-745-6100 or 1-800-679-0775 (toll-free) or submit a clinical trials inquiry form.