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).
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 first-in-human trial are to assess the safety and tolerability
of CUE-101 in subjects with recurrent/metastatic HNSCC 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. This will be an open-label multicenter phase I trial
conducted in the U.S. involving approximately 50 patients.
1. 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 patient's disease. Patients must also be willing and able to comply with
study procedures, including the acquisition of specified research specimens.
2. Age ≥ 18 years old
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4. Life expectancy ≥ 12 weeks
5. 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.
6. Recurrent and metastatic HNSCC that has progressed following at least 1 prior systemic
therapy. Patients must have received platinum-based chemotherapy and been offered
checkpoint immunotherapy.The requirement for prior systemic therapy may be waived if a
patient was intolerant of or refused standard first or second-line therapies.
7. Patient must have HLA-A*0201 genotype as determined by genomic testing performed at a
central laboratory determined by the Sponsor prior to enrollment.
8. Patient 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 patients 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.
9. All tumors must have histologically or cytologically confirmed diagnoses. Laboratory
10. Acceptable laboratory parameters as follows:
1. Platelet count ≥ 100 x 103/µL
2. Hemoglobin ≥ 9.0 g/dL
3. Absolute neutrophil count ≥ 1.5 × 103/µL in the absence of any growth factor
support within 2 weeks prior to the initiation of study drug
4. ALT or AST ≤ 3.0 × upper limit of normal (ULN); for patients with hepatic
metastases, ALT and AST ≤ 5 × ULN
5. Total bilirubin ≤ 1.5 × ULN, except patients with Gilbert's syndrome, who may
enroll if the conjugated bilirubin (total and direct) is within normal limits
6. Creatinine < 1.5 mg/dL, or a calculated or measured creatinine clearance > 30
11. Female patients 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 patients 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 patients, 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.
12. Non-vasectomized male patients with partners of childbearing potential must use
barrier contraception. In addition, male patients should also have their partners use
another method of contraception from the time of consent through 30 days after
discontinuation of study drug administration
13. Female patients should not be pregnant or plan to become pregnant during the course of
14. Female patients must not be breastfeeding. Previous Checkpoint Inhibitor Therapy
15. Patients 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. (see also Exclusion Criteria 10). Note that
patients who experienced previous hypothyroidism toxicity on a checkpoint inhibitor
are eligible to enter study regardless of CTCAE Grade resolution as long as the
patient is well controlled on thyroid replacement hormone.
1. Patients with symptomatic central nervous system (CNS) metastases must have been
treated, be asymptomatic, and not have any of the following at the time of enrollment:
1. Need for concurrent treatment for the CNS disease (eg, surgery, radiation,
corticosteroids > 10 mg prednisone / day or equivalent);
2. 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
3. Concurrent leptomeningeal disease or cord compression.
2. Patients with any history of known or suspected autoimmune disease with the specific
exceptions of the following:
2. Resolved childhood atopic dermatitis
3. Psoriasis (with exception of psoriatic arthritis) not requiring systemic
treatment (within the past 2 years)
4. Patients with a history of Grave's disease that are now euthyroid clinically and
by laboratory testing
3. History of prior allogeneic bone marrow, stem-cell or solid organ transplantation.
4. Treatment with any systemic anti-neoplastic therapy, or investigational therapy within
the 2 weeks prior to the initiation of study drug administration. Patients may be on
an investigational or other anti-neoplastic therapy during the screening phase of the
5. Treatment with radiation therapy within 2 weeks prior to the initiation of study drug
6. 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.
7. History of clinically significant cardiovascular disease including, but not limited
1. Myocardial infarction or unstable angina within the 16 weeks prior to the
initiation of study drug
2. Clinically significant cardiac arrhythmias
3. Uncontrolled hypertension: systolic blood pressure (BP) >180 mmHg, diastolic BP
4. Deep vein thrombosis, pulmonary embolism, stroke, or transient ischemic attack
within the 16 weeks prior to the initiation of study drug
5. QTcB prolongation > 480 msec
6. Congestive heart failure (New York Heart Association class III- IV)
7. Pericarditis/clinically significant pericardial effusion
8. Clinically significant pulmonary compromise (eg, requirement for supplemental oxygen)
9. Clinically significant GI disorders including:
1. History of GI perforation within 1 year prior to study drug administration.
Patients 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;
2. History of clinically significant GI bleeding within 3 months prior to the
initiation of study drug;
3. History of acute pancreatitis within 3 months prior to the initiation of study
4. 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.
10. Patients who experienced the following immune checkpoint inhibitor-related AEs are
ineligible even if the AE resolved to ≤ Grade 1 or baseline:
1. ≥ Grade 3 ocular AE
2. Changes in liver function tests that met the criteria for Hy's Law (> 3 × ULN of
either ALT/AST with concurrent >2 × ULN of total and direct bilirubin and without
3. ≥ Grade 3 neurologic toxicity
4. ≥ Grade 3 colitis
5. ≥ Grade 3 renal toxicity
11. Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral
treatment within 7 days prior to the initiation of study drug. Patients 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.
12. Known positive testing for human immunodeficiency virus or history of acquired immune
13. 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
14. Second primary invasive malignancy that has not been in remission for greater than 2
years. Exceptions that do not require a 2-year remission include: non- melanoma skin
cancer; cervical carcinoma in situ on biopsy; or squamous intraepithelial lesion on
Pap smear; localized prostate cancer (Gleason score < 6); or resected melanoma in
15. History of trauma or major surgery within 4 weeks prior to the initiation of study
16. Any serious underlying medical or psychiatric condition that would impair the ability
of the patient to receive or tolerate the planned treatment at the investigational
17. Known hypersensitivity to recombinant proteins, polysorbate 80 or any excipient
contained in the drug formulation for CUE-101.
18. Vaccination with any live virus vaccine within 4 weeks prior to the initiation of
study drug administration. Inactivated annual influenza vaccination is allowed.
19. Dementia or altered mental status that would preclude understanding and rendering of
20. Active or history of alcohol or other substance abuse within 1 year prior to the
initiation of study drug administration.
21. Any investigative site personnel directly affiliated with this study.
22. Prisoners or other individuals who are involuntarily detained.
23. Any issue that would contraindicate the patient's participation in the study or
confound the results of the study.