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

NCT03258008 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 2017-0145
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

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

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)

  Overall Response Rate assessed by RECIST 1.1 Criteria

  9 weeks from start of treatment

Secondary Outcomes (3)

• Adverse Events of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)

  Baseline, and continuously throughout the study at the beginning of each subsequent cycle up to 2 years

• Response Rate by irRC of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)

  Every-8-week schedule beginning from the first on-study assessment on Week 9 up to 2 years

• Progression Free Survival (PFS) of Utomilumab Combined With ISA 101b in Patients With Incurable Human Papillomavirus - Positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OPSCC)

  Every-8-week schedule beginning from the first on-study assessment on Week 9 up to 2 years

Study Arms (1)

Utomilumab + ISA101b

EXPERIMENTAL

Utomilumab 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.

Drug: Utomilumab; Biological: ISA101b

Interventions

Utomilumab DRUG

Utomilumab given by vein on Cycle 1 Day 1. Cycle 1-2 100 mg, Cycle 3-12 50 mg until progressive disease, toxicity, or 1 yr.

Also known as: PF-05082566, Anti-CD137

Utomilumab + ISA101b

ISA101b BIOLOGICAL

ISA101b 100 mcg/peptide given subcutaneously every 4 weeks x 3 doses beginning cycle 1 day 1.

Utomilumab + ISA101b

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study.
• Men and women \>/= 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of \</= 1.
• Subjects with histologically- or cytologically-documented incurable Human Papillomavirus (HPV)-positive OPSCC. HPV-16 serotype will be assessed by Cervista assay.
• Subjects can be treatment naïve or may have had two prior regimens for recurrent cancer. They must be naive to treatment with PD-1/L1 or CTLA-4 inhibitors.
• Subjects must have progression within 6 months of platin exposure during definitive or palliative therapy.
• Target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site.
• Subject entering the study will need to consent for mandatory biopsy at study entrance and as an optional procedure prior to C3 for biomarker evaluation. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient.
• Prior chemotherapy, 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.
• 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).
• 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.
• 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.
• Women must not be breastfeeding.
• 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).

You may not qualify if:

• 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.
• Subjects with carcinomatous meningitis.
• 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.
• 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.
• Prior therapy with anti-CD137 or ISA101.
• Subjects with a history of interstitial lung disease.
• Other active malignancy requiring concurrent intervention.
• 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.
• Subjects with toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue that have not resolved to grade 1 (NCI CTCAE version 4.03) or baseline before administration of study drug.
• 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.
• Treatment with any investigational agent within 28 days of first administration of study treatment.
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection.
• History of allergy or intolerance (unacceptable adverse event) to study drugs components.
• WOCBP who are pregnant or breastfeeding.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• ISA Pharmaceuticals B.V.: collaborator
• Pfizer: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Papillomavirus Infections

Interventions

utomilumab

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. John Heymach, PHD-Chair, Thoracic-Head & Neck Med Onc
• Organization: UT MD Anderson Cancer Center

jheymach@mdanderson.org

(713) 792-6363

Study Officials

• Bonnie S. Glisson, BS,MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2017
• First Posted: August 22, 2017
• Study Start: April 4, 2018
• Primary Completion: November 5, 2021
• Study Completion: November 5, 2021
• Last Updated: December 16, 2022
• Results First Posted: December 16, 2022

Record last verified: 2022-11

Locations

US (1)