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

Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorGustave Roussy, Cancer Campus, Grand Paris

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

  • HPVDC injection level dose 1

    Biological/Vaccine

    patient receive 3 injections of vaccine at the same level dose

  • placebo injection level dose 1

    Biological/Vaccine

    patient receive 3 injections of vaccine at the same level dose

  • HPVDC injection level dose 2

    Biological/Vaccine

    patient receive 3 injections of vaccine at the same level dose

  • placebo injection level dose 2

    Biological/Vaccine

    patient receive 3 injections of vaccine at the same level dose

Treatment groups

24 Participants
are divided into 4 treatment groups
Group A: level dose 1 HPVDC injectionExperimental treatment 1 intervention
Group B: level dose 1 placebo injectionPlacebo comparator 1 intervention
Group C: level dose 2 HPVDC injectionExperimental treatment 1 intervention
Group D: level dose 2 placebo injectionPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

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.

Time frame
at the end of the study, 24 months after the first inclusion
2

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").

Time frame
1year after the last visit of last patient

Secondary outcomes

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.