Therapeutic Vaccine in Patients With Human Papillomavirus HPV-positive Oropharyngeal Cancer

NCT06007092 | Recruiting Phase 1 DMC

• 2 other identifiers: 2022-502930-25-002022/3459
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a multicentric double-blind placebo-controlled dose escalation trial of a CD40HVac vaccine (humanized anti-CD40 mAb fused to HPV16 E6/E7 oncoproteins) adjuvanted with poly-ICLC (Hiltonol) in patients with HPV16 oropharyngeal carcinoma with no evidence of residual or recurrent disease after surgery and/or radiochemotherapy. The primary objective is to determine the recommended phase 2 dose (RP2D) of a poly-ICLC(Hiltonol)-adjuvanted CD40HVac vaccine according to the safety and the capacity to elicit immune responses of different doses Two dose levels of poly-ICLC-adjuvanted CD40.HVac will be explored

• 1st dose level: CD40.HVac 1.0 mg, with 1.0 mg poly-ICLC
• 2nd dose level: CD40.HVac 3.0 mg, with 1.0 mg poly-ICLC The safety data will be reviewed by an IDSMB that will give recommendations.

Conditions

Head and Neck Carcinoma; Adult Disease

Outcome Measures

Primary Outcomes (2)

• immunological outcomes: The frequency (%) of HPV16-specific T cells

  The primary immunological outcomes is: The frequency (%) of HPV16-specific T cells will be evaluated using Activation Induced Marker (AIM) assay using CD69 and CD137 (4-1BB) activation markers after a 24 hours stimulation using two validated tests routinely used in vaccine studies including ICS and AIM assays. These tests will be performed in all collected samples at W0, W2, W6, W26 and W48 for the durability of the responses.

  at the end of the study, 24 months after the first inclusion

• recommended phase 2 dose (mg) (RP2D) of poly-ICLC-adjuvanted CD40HVac

  The recommended phase 2 dose (RP2D) of poly-ICLC-adjuvanted CD40HVac will be determined by the Extensive Steering Committee according to the safety analysis and to the capacity of the vaccine to elicit immune responses. The capacity to elicit immune response will be used to choose the RP2D in the event that several doses of vaccine are acceptable in terms of safety (i.e. that meet of the "go-criterion").

  1year after the last visit of last patient

Study Arms (4)

level dose 1 HPVDC injection

EXPERIMENTAL

10 patients with experimental injection at 1.0 mg

Biological: HPVDC injection level dose 1

level dose 1 placebo injection

PLACEBO COMPARATOR

2 patients with experimental injection at 1.0 mg

Biological: placebo injection level dose 1

level dose 2 HPVDC injection

EXPERIMENTAL

10 patients with experimental injection at 3.0 mg

Biological: HPVDC injection level dose 2

level dose 2 placebo injection

PLACEBO COMPARATOR

2 patients with experimental injection at 3.0 mg

Biological: placebo injection level dose 2

Interventions

HPVDC injection level dose 1 BIOLOGICAL

patient receive 3 injections of vaccine at the same level dose

level dose 1 HPVDC injection

placebo injection level dose 1 BIOLOGICAL

patient receive 3 injections of vaccine at the same level dose

level dose 1 placebo injection

HPVDC injection level dose 2 BIOLOGICAL

patient receive 3 injections of vaccine at the same level dose

level dose 2 HPVDC injection

placebo injection level dose 2 BIOLOGICAL

patient receive 3 injections of vaccine at the same level dose

level dose 2 placebo injection

Eligibility Criteria

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

You may qualify if:

• Males and females ≥ 18 years of age.
• Willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study.
• Subjects with histologically confirmed oropharyngeal squamous cell carcinoma.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• 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.
• 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).
• 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)
• 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
• 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);

You may not qualify if:

• 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.
• 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.
• 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.
• 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.
• 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.
• Prior treatment with therapeutic anti-HPV vaccines.
• Invasive surgery (defined as surgical intervention requiring general or spinal anesthesia, and hospital admission) within 28 days prior to start of study treatment.
• Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus or hepatitis C virus.
• Patient with active infection must be postponed until infection resolution
• 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.
• History of organ transplantation, including allogenic peripheral stem cell or bone marrow transplantation.
• Participation in another clinical study with an investigational product during the last 6 months and while on study treatment
• 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.
• 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,

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead
• LinKinVax: collaborator

Study Sites (1)

Gustave Roussy

Villejuif, 94 805, France

RECRUITING

MeSH Terms

Conditions

Disease

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Caroline EVEN, Dr

  Gustave Roussy, Cancer Campus, Grand Paris

  STUDY CHAIR

Central Study Contacts

Philippe GORPHE, PhD

CONTACT

+33 (0)1 42 11 42 11; philippe.gorphe@gustaveroussy.fr

Caroline EVEN, Dr

CONTACT

+33 (0)1 42 11 42 11; Caroline.even@gustaveroussy.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: double blinded
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Within each group, patients will be randomized between poly-ICLC- adjuvanted CD40HVac or placebo in a 5:1 ratio. 12 patients will be treated at each dose level (10 with vaccine and 2 with placebo). The patients will receive three subcutaneous injections of a poly-ICLC- adjuvanted CD40HVac or placebo: * The first injection will occur at week 0 * The second injection will occur at week 4 (±7 days) * The third injection will occur at week 24 (±7 days)

Study Record Dates

• First Submitted: August 2, 2023
• First Posted: August 23, 2023
• Study Start: July 31, 2023
• Primary Completion: November 1, 2025
• Study Completion (Estimated): August 1, 2026
• Last Updated: December 1, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)