Clinical Trials /

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

NCT03978689

Description:

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).

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1 Study in Patients With HPV+ Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma
  • Official 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)

Clinical Trial IDs

  • ORG STUDY ID: Cue-101-01
  • NCT ID: NCT03978689

Conditions

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

Interventions

DrugSynonymsArms
CUE-101CUE-101 dose escalation and expansion

Purpose

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).

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 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.
    

Trial Arms

NameTypeDescriptionInterventions
CUE-101 dose escalation and expansionExperimentalCUE-101 Monotherapy IV infusion
  • CUE-101

Eligibility Criteria

        Inclusion Criteria:

          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
             Features

         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
                  mL/min.

             Reproductive Features

         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
             the trial.

         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.

        Exclusion Criteria:

          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:

               1. Vitiligo

               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
             study.

          5. Treatment with radiation therapy within 2 weeks prior to the initiation of study drug
             administration.

          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
             to:

               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
                  >100 mmHg

               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. Myocarditis

          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
                  drug; and/or

               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
                  alternate etiology)

               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
             deficiency syndrome.

         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
             reaction.

         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
             situ.

         15. History of trauma or major surgery within 4 weeks prior to the initiation of study
             drug administration.

         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
             site.

         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
             informed consent.

         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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicity
Time Frame:36 months
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Overall response rate (ORR) per RECIST 1.1
Time Frame:36 months
Safety Issue:
Description:Complete and partial responses as well as stable disease parameters will be followed

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Cue Biopharma

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