Clinical Trials /

Utomilumab and ISA101b Vaccination in Patients With HPV-16-Positive Incurable Oropharyngeal Cancer

NCT03258008

Description:

The goal of this clinical research study is to learn if utomilumab, when given with ISA101b, is able to shrink or slow the growth of tumors in patients with incurable HPV+ oropharyngeal squamous cell carcinoma. This is an investigational study. Utomilumab and ISA101b are not FDA approved or commercially available. They are currently being used for research purposes only. The study doctor can explain how the study drugs are designed to work. Up to 27 participants will be enrolled. All will take part at MD Anderson.

Related Conditions:
  • Oropharyngeal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Utomilumab and ISA101b Vaccination in Patients With HPV-16-Positive Incurable Oropharyngeal Cancer
  • Official Title: Phase II Trial of Utomilumab and ISA101b Vaccination in Patients With HPV-16-Positive Incurable Oropharyngeal Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2017-0145
  • NCT ID: NCT03258008

Conditions

  • Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites
  • Malignant Neoplasms of Lip Oral Cavity and Pharynx
  • Oropharyngeal Cancer

Interventions

DrugSynonymsArms
UtomilumabPF-05082566, Anti-CD137Utomilumab + ISA101b
ISA101bUtomilumab + ISA101b

Purpose

The goal of this clinical research study is to learn if utomilumab, when given alone or combined with ISA101b, is able to shrink or slow the growth of tumors in patients with incurable HPV+ oropharyngeal squamous cell carcinoma.

Detailed Description

      Study Groups:

      If participant is found to be eligible to take part in this study, participant will be
      assigned to a study group based on which type of HPV is found in the tumor. Participants with
      HPV-16 will be assigned to Group 1. Those with other types will be assigned to Group 2. Each
      group will enroll up to 22 participants.

        -  If participant is in Group 1, participant will receive utomilumab and ISA101b.

        -  If participant is in Group 2, participant will receive utomilumab alone.

      All participants in groups 1 and 2 will receive the same dose of utomilumab.

      Study Drug Administration:

      There are 28 days in each study cycle.

      Participant will receive utomilumab by vein every 4 weeks for up to 12 doses beginning on
      Cycle 1 Day 1. The drug will be given over about 1 hour each time participant receives it.

      If participant is in Group 1, participant will receive ISA101b as an injection under the skin
      every 4 weeks for 3 doses. Participant will receive 2 injections each time. One may be in
      participant's arm and one in participant's leg.

      Length of Study:

      Participant may continue taking utomilumab for up to 1 year as long as participant's doctor
      thinks it is in participant's best interest. Participant will no longer be able to take the
      study drug(s) if intolerable side effects occur or if participant is unable to follow study
      directions. Participant may not be able to take the study drug(s) if the disease gets worse,
      which is explained below.

      Participation on the study will be over after the follow-up visits.

      Study Visits:

      On Day 1 of Cycles 1-12:

        -  Participant will have a physical exam.

        -  Blood (about 1 tablespoon) and urine will be collected for routine tests, thyroid
           function tests, and liver function tests.

        -  If participant can become pregnant, blood (about ½ teaspoon) or urine will be collected
           for a pregnancy test.

        -  During Cycles 1, 2, 3, 4, 8, and 12, blood (up to 10 tablespoons) will be drawn for
           biomarker testing (including genetic biomarkers).

      At the end of Cycle 2 and every 8 weeks after that, participant will have an MRI or CT scan
      to check the status of the disease.

      Study Continuation:

      If the disease appears to have gotten worse, participant may still be eligible to continue
      receiving participant's assigned study drug(s). This is because participant may be
      benefitting from the study drug(s) even though the tumor(s) got larger. Participant's doctor
      will discuss this with participant.

      If this happens, participant's doctor will talk to participant about whether or not
      participant wants to continue. If participant does continue taking part in the study,
      participant will follow the study visits as described above.

      However, there are risks of continuing to receive the study drug(s) because the disease may
      actually be getting worse. Participant is still at risk for side effects due to utomilumab
      and ISA101b. Continuing on this study could also delay starting other treatments. The disease
      may get worse to the point that participant is no longer able to receive other treatments.
      There are also risks from the additional tests that may be performed, such as biopsies and
      blood draws. Participant and participant's doctor will discuss these possible risks, and
      participant will be asked to decide if participant wants to continue receiving the study
      drug(s).

      End-of-Treatment and Follow-up Visits:

      At about 30 days after participant's last study drug dose:

        -  Participant will have a physical exam.

        -  Blood (about 1 tablespoon) and urine will be collected for routine tests, thyroid
           function tests, and liver function tests.

        -  If participant is able to become pregnant, blood (about ½ teaspoon) or urine will be
           collected for a pregnancy test.

      At about 70 days after participant's last study drug dose:

        -  Participant will have a physical exam.

        -  Blood (about 1 tablespoon) and urine will be collected for routine tests, thyroid
           function tests, and liver function tests.

        -  If participant is able to become pregnant, blood (about ½ teaspoon) or urine will be
           collected for a pregnancy test.

      Participant will also be called every 3 months until the study ends and asked about
      participant's health. Each call should last about 10-15 minutes.

      If participant stopped taking the study drug for reasons other than the disease getting
      worse, participant will continue to have MRI/CT scans every 8 weeks. If the disease appears
      to get worse, or participant starts a new anticancer therapy, these scans will stop.

      Every 8 weeks for up to 18 months after your 70-day follow-up visit:

        -  Participant will have a physical exam.

        -  Blood (about 1 tablespoon) and urine will be collected for routine tests, thyroid
           function tests, and liver function tests.

      This is an investigational study. Utomilumab and ISA101b are not FDA approved or commercially
      available. They are currently being used for research purposes only. The study doctor can
      explain how the study drugs are designed to work.

      Up to 44 participants will be enrolled. All will take part at MD Anderson.
    

Trial Arms

NameTypeDescriptionInterventions
Utomilumab + ISA101bExperimentalUtomilumab by vein every 4 weeks for up to 12 doses beginning on Cycle 1 Day 1. ISA101b as an injection under the skin every 4 weeks for 3 doses. Participants receive 2 injections each time.
  • Utomilumab
UtomilumabExperimentalUtomilumab by vein every 4 weeks for up to 12 doses beginning on Cycle 1 Day 1.
  • Utomilumab

Eligibility Criteria

        Inclusion Criteria:

          1. Subjects must have signed and dated an IRB/IEC approved written informed consent form
             in accordance with regulatory and institutional guidelines. This must be obtained
             before the performance of any protocol related procedures that are not part of normal
             subject care.

          2. Subjects must be willing and able to comply with scheduled visits, treatment schedule,
             laboratory tests and other requirements of the study.

          3. Men and women >/= 18 years of age.

          4. Eastern Cooperative Oncology Group (ECOG) performance status of </= 1.

          5. Subjects with histologically- or cytologically-documented incurable Human
             Papillomavirus (HPV)-positive OPSCC. HPV-16 serotype will be assessed by Cervista
             assay.

          6. Subjects can be treatment naïve or may have had two prior regimens, including PD-1
             inhibitors.

          7. Subjects must have measurable disease by CT or MRI per RECIST 1.1 criteria;
             Radiographic Tumor Assessment performed within 28 days of study inclusion.

          8. Target lesions may be located in a previously irradiated field if there is documented
             (radiographic) disease progression in that site.

          9. Subject entering the study will need to consent for mandatory biopsy at study entrance
             and as an optional procedure at Week 9 for biomarker evaluation. Biopsy should be
             excisional, incisional or core needle. Fine needle aspiration is insufficient.

         10. Prior chemotherapy, immunotherapy, monoclonal antibody therapy, must have been
             completed at least 4 weeks prior to start. Radiotherapy or radiosurgery must have been
             completed at least 2 weeks prior to start.

         11. All baseline laboratory requirements will be assessed and should be obtained within
             -14 days of study registration. Screening laboratory values must meet the following
             criteria i) White blood cells (WBCs) >/= 2000/microL ii) Neutrophils >/= 1500/microL
             iii) Platelets >/= 100 x 10^3/microL iv) Hemoglobin >/= 9.0 g/dL Patients must not be
             transfused for at least 14 days prior to study entry v) Serum creatinine of </=1.5 x
             upper limit of normal(ULN) or creatinine clearance(CrCl) > 50 mL/minute (using
             Cockcroft/Gault formula) Female CrCl= 0.85 x [(140 - age in years) x weight in kg]/(72
             x serum creatinine in mg/dL) Male CrCl= 1.00 x [(140 - age in years) x weight in
             kg]/(72 x serum creatinine in mg/dL) vi) AST </= 2.5 x ULN vii) ALT </= 2.5 x ULN
             viii) Total bilirubin</= 1.5 x ULN (except subjects with Gilbert Syndrome who must
             have total bilirubin <3.0 mg/dl).

         12. Women of childbearing potential (WOCBP) must use method(s) of contraception for 30
             days + 5 half-lives (60 days) of the study drugs. For a teratogenic study drug and/or
             when there is insufficient information to assess teratogenicity (preclinical studies
             have not been done), a highly effective method(s) of contraception (failure rate of
             less than 1% per year) is required. Highly effective birth control in this study is
             defined as a double barrier method. Examples include a condom (with spermicide) in
             combination with a diaphragm, cervical cap, or intrauterine device (IUD). The
             individual methods of contraception should be determined in consultation with the
             investigator.

         13. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L
             or equivalent units of HCG) within 24 hours prior to the start of investigational
             product.

         14. Women must not be breastfeeding.

         15. Men who are sexually active with WOCBP must use any contraceptive method with a
             failure rate of less than 1% per year. The investigator shall review contraception
             methods and the time period that contraception must be followed. Men that are sexually
             active with WOCBP must follow instructions for birth control for a period of 90 days
             plus the time required for the investigational drug to undergo 5 half- lives (60
             days).

        Exclusion Criteria:

          1. Subjects with active CNS metastases are excluded. Subjects are eligible if CNS
             metastases are adequately treated and subjects are neurologically returned to baseline
             (except for residual signs or symptoms related to the CNS treatment) for at least 4
             weeks prior to enrollment. In addition, subjects must be either off corticosteroids,
             or on a stable or decreasing dose of </= 10 mg daily prednisone (or equivalent) for 2
             weeks.

          2. Subjects with carcinomatous meningitis.

          3. Subjects with active, known or suspected systemic autoimmune disease. Subjects with
             vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune
             thyroiditis only requiring hormone replacement, or conditions not expected to recur in
             the absence of an external trigger are permitted to enroll.

          4. Subjects with a condition requiring systemic treatment with either corticosteroids
             (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14
             days of start. Inhaled or topical steroids, and adrenal replacement steroid doses > 10
             mg daily prednisone equivalent, are permitted in the absence of active autoimmune
             disease.

          5. Prior therapy with anti-CD137 or ISA101.

          6. Subjects with a history of interstitial lung disease.

          7. Other active malignancy requiring concurrent intervention.

          8. Subjects with previous malignancies (except non-melanoma skin cancers, and the
             following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia,
             melanoma, or breast) are excluded unless a complete remission was achieved at least 2
             years prior to study entry AND no additional therapy is required during the study
             period.

          9. Subjects with toxicities attributed to prior anti-cancer therapy other than alopecia
             and fatigue that have not resolved to grade 1 (NCI CTCAE version 4) or baseline before
             administration of study drug.

         10. Subjects who have not recovered from the effects of major surgery or significant
             traumatic injury at least 14 days before the first dose of study treatment.

         11. Treatment with any investigational agent within 28 days of first administration of
             study treatment.

         12. Known history of testing positive for human immunodeficiency virus (HIV) or known
             acquired immunodeficiency syndrome (AIDS).

         13. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus
             ribonucleic acid (HCV RNA) indicating acute or chronic infection.

         14. History of allergy or intolerance (unacceptable adverse event) to study drugs
             components.

         15. WOCBP who are pregnant or breastfeeding.

         16. Women with a positive pregnancy test at enrollment or prior to administration of study
             medication.

         17. Any other serious or uncontrolled medical disorder, active infection, physical exam
             finding, laboratory finding, altered mental status, or psychiatric condition that, in
             the opinion of the investigator, would limit a subject's ability to comply with the
             study requirements, substantially increase risk to the subject, or impact the
             interpretability of study results.

         18. Prisoners or subjects who are involuntarily incarcerated.

         19. Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical (eg, infectious disease) illness.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate of Utomilumab Alone and Combined with ISA 101b
Time Frame:9 weeks from start of treatment
Safety Issue:
Description:Overall Response Rate assessed by RECIST 1.1 Criteria

Secondary Outcome Measures

Measure:Adverse Events of Utomilumab Alone and Combined with ISA 101b
Time Frame:Baseline, and continuously throughout the study at the beginning of each subsequent cycle up to 2 years
Safety Issue:
Description:Adverse events assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Measure:Response Rate by irRC of Utomilumab Alone and Combined with ISA 101b
Time Frame:Every-8-week schedule beginning from the first on-study assessment on Week 9 up to 2 years
Safety Issue:
Description:Response rate monitored by radiographic assessment.
Measure:Immune-Related Progression Free Survival (PFS) of Utomilumab Alone and Combined with ISA 101b
Time Frame:Every-8-week schedule beginning from the first on-study assessment on Week 9 up to 2 years
Safety Issue:
Description:PFS monitored by radiographic assessment.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Malignant neoplasms of lip oral cavity and pharynx
  • Malignant neoplasms of ill-defined secondary and unspecified sites
  • Oropharyngeal Cancer
  • Oropharyngeal squamous cell carcinoma
  • OPSCC
  • Human Papillomavirus - positive (HPV+)
  • Utomilumab
  • PF-05082566
  • Anti-CD137
  • ISA101b

Last Updated

August 21, 2017