An experimental study in men and women with head and neck cancer to test the safety, tolerability and the effects of addition of a vaccine directed against an infection with Human Papilloma virus Type 16 (HPV16) in combination with an antibody that activate part of the immune system

Phase 1

• Conditions: HPV16-Positive Platin-Resistant Oropharyngeal Cancer (OPC); MedDRA version: 20.0 Level: PT Classification code 10031098 Term: Oropharyngeal cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-000789-13-GB
• Lead Sponsor: ISA Therapeutics B.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-07-20
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 164

Inclusion Criteria

1. Males and females, = 18 years of age.
2. Sign and date an IRB/IEC-approved written informed consent form.
3. Be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study.
4. Diagnosed with histologically confirmed recurrent or metastatic HPV16 positive OPC, not amenable to any therapy with curative intent. Subjects with HPV16 positive squamous cell carcinoma (SCC) of occult primary site, presenting with lymph node(s) in the neck, are also eligible.
5. HPV16 genotyping determined by a specified central reference laboratory with an established polymerase chain reaction (PCR)-based assay.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
7. Tumor progression or recurrence on or after platinum-containing chemotherapy for the treatment of primary, metastatic or recurrent disease, or within 6 months of platinum containing chemotherapy administered as part of neo-adjuvant or adjuvant therapy.
8. Measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension with a minimum size of 10 mm by computed tomography (CT) scan or magnetic resonance imaging (MRI) per RECIST 1.1 criteria. Indicator lesions must not have been previously treated with surgery, radiation therapy, or radiofrequency ablation, unless there is documented progression after therapy.
9. Fresh tumor tissue must be provided for biomarker correlative studies unless the investigator determines that this could impose a significant risk to the subject after discussion with Medical Monitor.
10. Prior curative radiation therapy must have been completed at least 8 weeks prior to study drug administration. Prior focal palliative radiotherapy must have been completed at least 2 weeks before study drug administration.
11. Screening laboratory values must meet the following criteria (using National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0) and should be obtained within 14 days prior to randomization:
i) White blood cell (WBC) count = 2 x 10 9/L
ii) Absolute neutrophil count (ANC) = 1.5 x 10 9/L
iii) Platelets = 100 x 10 9/L
iv) Hemoglobin = 9.0 g/dL
v) Serum creatinine = 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl)> 40 mL/min
vi) Hepatic function:
a. Total bilirubin = 1.5 x ULN (if liver metastases = 3 x ULN). Subjects with Gilbert’s Disease and total bilirubin up to 3 x ULN may be eligible if total bilirubin < 3.0 mg/dL.
b. Transaminases (ALT and AST) = 3 x ULN (or = 5.0 x ULN, if liver metastases)
c. Alkaline phosphatase = 2.5 x ULN (or = 5.0 x ULN, if liver or bone metastases)

Note for subjects with hepatic metastases: If transaminase levels (aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]) > 3 x but = 5 x ULN, total bilirubin must be = 1.5 x ULN. If total bilirubin > 1.5 x but = 3 x ULN, both transaminases (AST and ALT) must be = 3 x ULN.

Note regarding drug induced liver failure (DiLi): According to Hy's Law of Drug Induced Liver Injury a drug causes hepatocellular injury, generally defined as an elevated ALT or AST by 3-fold

Exclusion Criteria

1. Subjects with known active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if these have been treated and there is no MRI (or CT scan where MRI is contraindicated) evidence of progression for at least 4 weeks after the completion of the last treatment. Base of skull involvement without definitive evidence of dural or brain parenchymal involvement is acceptable. Subjects being treated with immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) should discontinue this therapy at least 2 weeks prior to entrance into the trial; patients requiring maintenance immunosuppressive doses of corticosteroids are excluded.
2. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
3. History of other malignancy = 3 years prior to entry into this trial with the exception of basal cell or squamous cell skin carcinoma which were treated with local resection only, OR carcinoma in situ of the cervix, prostate or breast, OR low grade non-muscle invasive superficial bladder cancer (TaLG)/carcinoma in situ of the bladder.
4. Subjects with active, known, diagnosed or suspected autoimmune disease. Subjects suffering from vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring thyroid hormone replacement therapy, or psoriasis not requiring systemic treatment can be enrolled.
5. Patients diagnosed with active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis or another condition requiring immunosuppressive doses of systemic medication such as systemic corticosteroids or absorbed topical corticosteroids (doses = 10 mg/day prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical corticosteroids and adrenal replacement doses < 10 mg daily prednisone or equivalent are permitted.
6. Prior treatment with an anti-PD-1 antibody (e.g., nivolumab, pembrolizumab, cemiplimab), as well as anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
7. Prior treatment with therapeutic anti-HPV vaccines including ISA101 or ISA101b. Subjects who have received a preventive HPV vaccine are allowed.
8. Grade 1 or greater toxicities attributed to systemic prior anti-cancer therapy other than alopecia, fatigue (NCI CTCAE), radiation dermatitis, laboratory abnormalities that are not considered clinically significant by the treating physician, before administration of study drug. Subjects with residual grade 1 toxicities or toxicities attributed to systemic prior anticancer therapy that have become chronic and are not expected to resolve, such as neuropathy after platinum based therapy, can be included in this trial.
9. Treatment with any chemotherapy, biological therapy for cancer, or investigational therapy unless five half-lives have elapsed.
10. Administration of any live vaccine within 30 days before first dose of study drug.
11. Uncontrolled infection with hum

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified