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)
Conditions
Sponsors
ISA Therapeutics B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
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 count (WBC) = 2/mL ii) Absolute neutrophil count (ANC) = 1.5/mL iii) Platelets = 100 x103/µL 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 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 or greater above the upper limit of normal, combined with an elevation of serum total bilirubin of greater than 2× the upper limit of normal, without findings of cholestasis (defined as serum alkaline phosphatase activity less than 2× the upper limit of normal). i) Calcium levels must be normalized and maintained within normal limits for study entry and on tre
Exclusion criteria
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 treatment is complete. Base of skull involvement without definitive evidence of dural or brain parenchymal involvement is acceptable. Subjects who require treatment with immunosuppressive doses of systemic corticosteroids (more than 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration. 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 within 28 days of first administration of study treatment. 10. Administration of any live vaccine within 30 days before first dose of study drug. 11. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus or hepatitis C virus, except for: - Subjects with HIV who have controlled infection (undetectable viral load and CD4 count above 350 cells/mm3 either spontaneously or on a stable antiviral regimen) are permitted. -
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective: To evaluate if the addition of ISA101b to cemiplimab results in improved overall response rate (ORR) compared to cemiplimab alone, according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by independent review. Primary Safety Objective: To assess the safety and tolerability of the combination of cemiplimab plus ISA101b compared to placebo plus cemiplimab.;Secondary Objective: - To compare the overall response rate and other clinical outcome parameters in patients being treated with cemiplimab and ISA101b, and cemiplimab only, with patients concurrently being treated with standard therapy with a registered anti-programmed cell death (PD) 1 inhibitor such as nivolumab or pembrolizumab (historical controls). - Duration of response (DOR) by independent review in subjects randomized to receive ISA101b + cemiplimab compared to placebo + cemiplimab. - Time to response (TTR) by independent review in subjects randomized to receive ISA101b + cemiplimab compared to placebo + cemiplimab. - Progression-free survival (PFS) by independent review in subjects randomized to receive ISA101b + cemiplimab compared to placebo + cemiplimab. The PFS rate at 6 months will also be compared. - Median overall survival (OS) in subjects randomized to receive ISA101b plus cemiplimab compared to placebo + cemiplimab. The OS rate at 12 months will also be compared.;Primary end point(s): Primary Efficacy Endpoint: ORR by independent review in subjects randomized to receive ISA101b plus cemiplimab compared to cemiplimab alone.;Timepoint(s) of evaluation of this end point: Continuously throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety endpoint: Frequency and severity of toxicity in subjects randomized to receive ISA101b plus cemiplimab compared to cemiplimab alone.;Timepoint(s) of evaluation of this end point: Continuously throughout the study | — |
Countries
Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactClinical Department
ISA Therapeutics B.V.
Outcome results
None listed