Therapeutic vaccine for HPV-positive oropharyngeal cancer

Multicentric Randomized Phase I/IIa Trial of the Safety and Immunogenicity of a Therapeutic Anti-HPV DC Targeting Vaccine in Patients With Human Papillomavirus (HPV)-Positive Oropharyngeal Cancer

This study is testing a new vaccine to see if it can help people with HPV-positive throat cancer stay cancer-free after their treatment.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris (Academic / other)
• Drugs / interventions: prednisone
• Locations: 1 site (Villejuif)
• Trial ID: NCT06007092 on ClinicalTrials.gov

What this trial studies

This multicentric, double-blind, placebo-controlled trial evaluates a CD40HVac vaccine combined with poly-ICLC in patients with HPV16-positive oropharyngeal carcinoma who have no residual disease after surgery or radiochemotherapy. The study aims to determine the recommended phase 2 dose by assessing safety and immune response across two different dosage levels. Participants will receive three subcutaneous injections of either the vaccine or a placebo, with a focus on eliciting an immune response against HPV-related cancer. The trial will involve randomization and a careful review of safety data by an independent monitoring board.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed HPV16-positive oropharyngeal squamous cell carcinoma who have completed curative treatment.

Not a fit: Patients with active disease or those who have not undergone comprehensive curative treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this vaccine could provide a novel therapeutic option for patients with HPV-positive oropharyngeal cancer, potentially improving long-term outcomes.

How similar studies have performed: While there have been studies exploring therapeutic vaccines for HPV-related cancers, this specific approach using CD40HVac is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Males and females ≥ 18 years of age.
2. Willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study.
3. Subjects with histologically confirmed oropharyngeal squamous cell carcinoma.
4. HPV16 genotyping determined by a specified central reference laboratory with an established polymerase chain reaction (PCR)- based assay on FFPE archived tumor biopsies (or 10 slices of 5µm).If local HPV16 genotype assessment has been performed, the subject can be enrolled if the result shows HPV16 positivity. Confirmation of HPV16 positive status will be performed retrospectively by the central laboratory on archived tissue. Formalin- fixed tumour biopsies or surgical piece before local radical treatment can be optionally available for translational research.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
6. Comprehensive curative treatment according to the disease stage and national guidelines, completed at least 16 weeks prior to study drug administration. The recommended duration between end of curative treatment and study drug administration is 18 to 20 weeks.
7. No evidence of residual or recurrent disease on the last assessment, comprising a physical examination, a head and neck CT-scan or a head and neck MRI, and a thoracic CT Scan (and TEP-scan only for patients traited by radiotherapy or radiochemotherapy without surgery).
8. Vaccination for Covid and Flu vaccines are authorised 4 weeks before or after the administration of poly-ICLC-adjuvanted CD40HVac (2 weeks during flu period for the Flu vaccine)
9. Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to randomization:

   i) White blood cell count (WBC) ≥ 2 x 109/L ii) Absolute neutrophil count (ANC) ≥ 1.5 x 109/L iii) Platelets ≥ 100 x 109/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 (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 vi) Hepatic function: Total bilirubin ≤ 1.5 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.Transaminases (ALT and AST) ≤ 3 x ULN, Alkaline phosphatase ≤ 2.5 x ULN
10. Participants who were born female: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test performed before randomisation and on the day of initial IMP administration (W0)

    • Reproductive status: if heterosexually active female, consistently using an effective method of contraception with partner for sexual activity that could lead to pregnancy from at least 21 days prior to enrolment through 4 months after the last administration.

    Effective contraception is defined as using any of the following methods:
    * Condoms (male or female) with or without a spermicide;
    * Intrauterine device (IUD);
    * Intrauterine hormone releasing system (IUS);
    * Hormonal contraception (progesterone only);
    * Successful vasectomy in the male partner (considered successful if a participant reports that a male partner has (i) documentation of azoospermia by microscopy, or (ii) a vasectomy more than 2 years ago with no resultant pregnancy despite unprotected sexual activity postvasectomy);
    * Or not be of reproductive potential, such as having reached menopause (no menses for 1 year without an alternative medical cause) or having undergone hysterectomy, bilateral oophorectomy, or tubal ligation.
    * Agree not to seek pregnancy including through alternative methods, such as artificial insemination or in vitro fertilization until 4 months after the last administration.

    Participants who were born male, if heterosexually active male, using an effective method of contraception with their partner from the first day of IMP administration until 4 months after the last administration. This also applies to sperm donation.
11. Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed.
12. Patients must be affiliated to a social security system or beneficiary of the same

Exclusion Criteria:

1. Clinical evidence on physical or radiological examination of residual or recurrent HPV-driven carcinoma on the primary site, in neck lymph nodes, or in any distant site metastasis.
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. Subjects with active, known, diagnosed or suspected auto-immune 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.
4. Patients diagnosed with active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis within the last 5 years, or another condition requiring immunosuppressive doses of 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.
5. Subjects requiring maintenance treatment with immunosuppressive doses of systemic corticosteroids. Subjects being treated with a short course of corticosteroids (\> 10 mg/day prednisone equivalents) should discontinue this therapy at least 2 weeks prior to start of study treatment.
6. Prior treatment with therapeutic anti-HPV vaccines.
7. Invasive surgery (defined as surgical intervention requiring general or spinal anesthesia, and hospital admission) within 28 days prior to start of study treatment.
8. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus or hepatitis C virus.
9. Patient with active infection must be postponed until infection resolution
10. Subjects with an uncontrolled or significant heart disease such as long QT syndrome with QTcF \> 480 ms on baseline ECG, NYHA III/IV or uncontrolled arrhythmia.
11. History of organ transplantation, including allogenic peripheral stem cell or bone marrow transplantation.
12. Participation in another clinical study with an investigational product during the last 6 months and while on study treatment
13. Vaccination for Covid and Flu vaccines is not permitted within 4 weeks prior the first vaccination with polyICLC adjuvanted CD40HPVac (2 weeks during flu period for the Flu vaccine.
14. Treatment is not permitted within 4 weeks prior the first vaccination and 4 months after the last injection. Furthermore, the use of this medication will be considered as a deviation to the protocol.

    * curative treatment within 12 weeks before the first injection,
    * Corticosteroids,
    * Live attenuated vaccines (such as measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever) or any vaccines that are not live attenuated (eg, tetanus, pneumococcal, Hepatitis A or B) except IMP vaccine.
    * Immunosuppressive medications (Not excluded: \[1\] corticosteroid nasal spray; \[2\] inhaled corticosteroids; \[3\] topical corticosteroids for mild, uncomplicated dermatitis; or \[4\] a single course of oral/parenteral corticosteroids at doses \< 2 mg/kg/day and length of therapy \< 11 days with completion at least 30 days prior to enrollment)
    * Blood products
    * Immunoglobin
    * Anti-tuberculosis drugs
    * Immunomodulators (such as cytokines or interferons) or immunosuppressive drugs during 8 weeks preceding the screening visit and as of 4 months after the last injection will not be allowed. If any patient needs chronic use of one of these medicine during this period, the subject will be withdrawn from the investigational product but should be followed at all visits as planned by the protocol
    * Antipyretic will not be allowed twelve (12) hours before immunization as preventive treatment of pain or fever.
15. Pregnant or breastfeeding women or intending to become pregnant during study
16. Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent

Where this trial is running

Villejuif

• Gustave Roussy — Villejuif, France (Recruiting)

Study contacts

• Study coordinator: Philippe GORPHE, PhD

Conditions Head and Neck Carcinoma; Adult Disease