An experimental study in men and women with head and neck cancer to test the efficacy, safety and tolerability of a vaccine directed against an infection with Human Papilloma virus Type 16 (HPV16) in combination with an antibody that activates part of the immune system
- Conditions
- Recurrent/metastatic HPV16- positive Oropharyngeal Cancer (OPC)MedDRA version: 21.0Level: PTClassification code 10031098Term: Oropharyngeal cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-003652-32-DE
- Lead Sponsor
- ISA Therapeutics B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 65
1. Men and women = 18 years of age.
2. Provide informed consent signed by study patient.
3. Willing and able to comply with site visits and study-related procedures and requirements.
4. Histologically confirmed recurrent or metastatic HPV16-positive Oropharyngeal Cancer (OPC)*. Patients with squamous cell carcinoma SCC of occult primary site, presenting with lymph node(s) limited only to the neck, are also eligible. Patients should have HPV16 positivity confirmed before being considered a candidate for this study, see inclusion criteria 5.
* Recurrent or metastatic disease in the context of this study if defined as recurrent, metastatic or advanced disease.
5. HPV16 genotyping as determined by a specified central reference laboratory with an established polymerase chain reaction (PCR)-based assay. If local HPV16 genotype assessment (PCR or in situ hybridization (ISH) has been performed, the patient can be enrolled if the result shows HPV16 positivity. Confirmation of HPV16 positive status will then subsequently have to be performed by the central laboratory.
6. Patients who have received a minimum total dose of 600 mg of pembrolizumab or 960 mg of nivolumab or equivalent anti-PD-1 antibody with or without chemotherapy for only 1st or 2nd line recurrent/metastatic HPV16-positive OPC. The last dose of anti-PD-1 must been no more than 6 months prior to enrollment into the trial. Progressive disease (PD) must have been diagnosed during or after anti-PD-1 therapy (but not longer than 6 months after the last dose). Prior treatment regimens must have included platrinum- based chemotherapy, 5-fluorouacil (5-FU) or an alternative fluoroparimidine, and cetuximab, if appropriate. Anti PD-1 therapy (as 1st or 2nd line for recurrent/metastatic HPV16 positive OPC) should have been the last treatment regimen that the patient received before entry into the current trial.
7. Prescreening consent only: ability to provide archived tumor sample (preferably tumor block or otherwise at least 10 unstained slides) to allow determination of HPV16-positive status by the central laboratory -or a local laboratory if applicable- using an investigational use only assay.
8. At least one measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST version 1.1 criteria. Target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site.
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
10. Adequate organ and bone marrow function documented by:
a. Hemoglobin = 8 g/dL
b. Absolute neutrophil count = 1.0 x 109/L
c. Platelet count = 75 x 109/L
d. Serum creatinine = 1.5 x upper limit of normal (ULN) and etimated glomerular filtration rate > 30 mL/ min/1.73m2. A 24-hour urine creatinine collection may substitute for the calculated creatinine clearance to meet eligibility criteria or creatinine clearance (CrCl) > 30 mL/min (using the Cockcroft-Gault formula):
Female CrCl = (140 - age in years) x weight in kg x 0.85
72 x serum creatinine in mg/dL
Male CrCl = (140 - age in years) x weight in kg x 1.00
72 x serum creatinine in mg/dL
e. Adequate hepatic function:
i. Total bilirubin = 1.5 x upper limit of normal (ULN) (=3 x ULN if tumor liver involvement)
ii. Aspartate Aminotransferase (AST) = 2.5 x ULN (=3 x ULN if tumor liver involvement)
iii. Alanine Aminotransferase (ALT) = 2.5 x ULN (=3 x ULN if tumor liver involvement)
iv. Alkaline Phosphatas
1. Invasive surgery (defined as surgical intervention requiring general or spinal anesthesia and hospital admission) within 4 weeks prior to start
of study treatment.
2. Patients who, after progressing on anti-PD-1, received additional anticancer therapy (chemotherapy, radiotherapy, experimental TKI's, immunotherapy, anti-EGFR antibodies, surgery). The following palliative treatments are allowed:
- palliative radiotherapy (but NOT for target lesions)
- palliative surgery
- bone resorptive therapy such as bisphosphonates and denosumab but only if patients have been on stable doses for > 4 weeks prior to first
dose of test treatment
3. Patients who have permanently discontinued anti-cancer immune modulating therapies due to drug-related toxicity.
4. Another malignancy that is progressing or requires active treatment and/or history of malignancy other than oropharyngeal cancer within 3
years of date of first planned dose of study drug, except:
a. Non-melanoma skin cancer that has undergone potentially curative therapy
b. In situ cervical carcinoma
c. Ductal carcinoma in situ of the breast
d. In-situ prostate cancer with non-detectable prostate specific antigen
e. Any tumor that has been deemed to be effectively treated with definitive local control (with or without continued adjuvant hormonal therapy), and the patient is deemed to be in complete remission for at least 2 years prior to randomization, and no additional therapy is required during the study period.
5. Any condition that requires ongoing/continuous corticosteroid therapy (> 10 mg prednisone/day or anti-inflammatory equivalent) within 1 week prior to the first dose of study therapy. Patients who require a brief course of steroids (up to 2 days in the week before enrollment) or physiologic replacement are not excluded.
6. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments. The following are not exclusionary: vitiligo, resolved childhood asthma , endocrinopathies that require only hormone replacement, or psoriasis that does not require systemic treatment.
7. Subjects with known brain metastases or leptomeningeal metastases.
8. Encephalitis, meningitis, organic brain disease (e.g. Parkinson's disease) or uncontrolled seizures in the year prior to first dose of study
therapy.
9. Known history of, or any evidence of interstitial lung disease, or active, non-infectious pneumonitis (in the past 5 years). A history of radiation pneumonitis in the radiation field is permitted.
10. Has participated in a study of an investigational agent or an investigational device, unless approved by the Sponsor.
11. Prior treatment with therapeutic anti-HPV vaccines including ISA101 or ISA101b. Patients who have received a preventive HPV vaccine are allowed.
12. 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.
13. Uncontrolled infection with HIV, hep B or hep C infection; or diagnosis of immunodeficiency.
allowed
14. Any infection requiring hospitalization or treatment with IV antiinfectives within 2 weeks of first dose of study therapy.
15. Receipt of a live vaccine within 4 weeks of planned start of study drug.
16. Allogeneic stem cell transplantation, or autologous stem cell transp
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • To estimate the clinical benefit of ISA101b plus cemiplimab after progression on prior anti-PD-1 therapy, as assessed by objective response rate (ORR) according to RECIST 1.1.;Secondary Objective: • To characterize the safety profile of ISA101b plus cemiplimab.<br>• To assess preliminary efficacy of ISA101b plus cemiplimab as measured by multiple criteria.<br>;Primary end point(s): • Objective Response Rate (ORR) based on radiographic response, measured by RECIST version 1.1.<br>;Timepoint(s) of evaluation of this end point: Continuously throughout the study
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Incidence and severity of TEAEs/AESIs/SAEs and =3 grade laboratory abnormalities during the treatment period and up to 105 days after the last dose of study treatment.<br>• Duration of Response (DOR).<br>• Progression-free Survival (PFS).<br>• Overall survival (OS) until death, loss to follow-up or termination of the study by the Sponsor.<br>;Timepoint(s) of evaluation of this end point: Continuously throughout the study