for people ages 18 years and up (full criteria)
at La Jolla, California and other locations
study start
estimated completion



This is a Phase 2, multicenter, open-label, 2-cohort (Locoregionally Advanced Cohort or Recurrent/Metastatic Cohort) study evaluating RP3 in combination with concurrent chemoradiation therapy (CCRT) followed by nivolumab (for the LA Cohort) or combined with chemotherapy and nivolumab (for the R/M Cohort) in patients with advanced, inoperable squamous cell carcinomas of the head and neck (SCCHN), including of the oral cavity, oropharynx, hypopharynx, larynx, or unknown primary.

Official Title

A Phase 2, Open-label, Multicenter Study Investigating Oncolytic Immunotherapy in Combination With Other Therapy in Patients With Locoregionally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck


RP3 is a genetically modified herpes simplex type 1 virus (HSV-1) that expresses exogenous genes (anti-CTLA-4 antibody, CD40 ligand and h4-1BBL) designed to directly kill tumor cells and generate a systemic anti-tumor immune response


Squamous Cell Carcinoma of Head and Neck, Locally Advanced Head and Neck Squamous Cell Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma, Squamous cell carcinomas of head and neck, Immunotherapy, Immuno-oncology, Oncolytic virus, Oncolytic immuno-gene therapy, Carcinoma, Squamous Cell Carcinoma, Recurrence, Paclitaxel, Carboplatin, Nivolumab, CCRT(concurrent chemoradiation therapy), carboplatin and paclitaxel


You can join if…

Open to people ages 18 years and up

  • Histological diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx or of a lymph node(s) anywhere in levels I to V of the neck that has been excluded clinically from association with cancer from a non-head and neck site
  • All patients Must be willing to consent to provide archival or fresh tumor biopsy samples obtained within 60 days prior to initiation of study treatment. Patients must also consent to provide on-treatment biopsies as per protocol.
  • At least 1 measurable lesion of ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes), in accordance with RECIST.
  • At least injectable tumors of at least 1 cm in aggregate overall longest diameter.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 -1.

    Locally Advanced Cohort Only • patients must not be amenable to surgery with curative intent Previously untreated high-risk disease meeting at least 1 of the following criteria:

  • Oral cavity, hypopharynx, larynx, oropharynx (p16 negative): Stage III/ IV Note: Cancers of the oral cavity, hypopharynx, and larynx are eligible irrespective of p16 status. These patients will not be stratified by p16 status.
  • For p16 positive oropharynx cancers, patients must have either
    • T3 and/or N2 or greater disease with active smoking and/or greater than 20 pack year smoking history OR
    • T4 and/or N3 disease irrespective of tobacco use
  • SCCHN of unknown primary Stage III/IV irrespective of p16 status or smoking status.
  • Eligible for definitive CCRT with curative intent.

    R/M Cohort Only

  • Has recurrent or metastatic SCCHN eligible for first line systemic therapy for R/M disease.
  • Has a PD-L1 CPS <20.

You CAN'T join if...

  • Primary tumors of nasopharynx, paranasal sinuses, nasal passages, salivary gland, thyroid or parathyroid gland, or skin.
  • Tumors with histopathology indicating the tumor has sarcomatous, sarcomatoid, verrucous, mixed, undifferentiated, or otherwise nonsquamous components.
  • Has an airway that is not deemed safe and stable on flexible fiberoptic laryngoscopy (FFL) performed by a head & neck cancer specialist within 7 days of first RP3 injection.
  • Has a baseline serum albumin (at Screening) <2.5 g/dL and/or evidence of cachexia or muscle wasting during physical exam at Screening.
  • Known acute or chronic hepatitis B or acute or chronic hepatitis C
  • Systemic infection requiring intravenous (IV) antibiotics
  • Active significant herpetic infections or prior complications of HSV-1 infection (eg, herpetic keratitis or encephalitis)
  • History of interstitial lung disease.
  • History of (noninfectious) pneumonitis that required steroids or has current pneumonitis.
  • Patients who require intermittent or chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir).
  • Administration of live vaccine within 28 days prior to the first dose of study treatment.
  • History of allergy or sensitivity to study drug components or prior monoclonal antibody treatment.
  • History of life-threatening toxicity related to prior immune treatment or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
  • History of viral infections according to the protocol
  • Treatment with botanical preparations within 2 weeks prior to treatment.
  • Major surgery ≤ 2 weeks prior to starting study treatment.

    LA Cohort only

  • Has received prior radiotherapy for SCCHN.
  • Has received any prior systemic therapy for SCCHN.

    R/M cohort only

  • Is eligible for radiation and/or surgery with curative intent.
  • Has received systemic therapy for recurrence or new (ie, not present at the time of initial diagnosis) metastases of SCCHN.
  • Received a paclitaxel-containing regimen as part of frontline treatment (prior to R/M disease) with a documented best response of stable disease (SD) or PD (patients who achieved a partial response [PR] or CR are eligible).
  • Received a carboplatin-containing regimen as part of frontline treatment (prior to R/M disease) with a documented best response of SD or PD (patients who achieved PR or CR are eligible).
  • Patients with known intolerance to carbo-platinum and/or paclitaxel, including hypersensitivity to Cremophor® EL (polyoxyethylated castor oil).
  • Previously received multiple courses of irradiation to the same anatomic site unless such patient has nondoubly-irradiated, measurable, injectable lesions, which are the only lesions to be used as target lesions (for nodal disease, only lesions in nodal basins that have been previously irradiated just once or not irradiated at all may be injected and/or used as target lesions).

    Note: Other protocol defined inclusion/exclusion criteria apply for each cohort


  • University of California San Diego, UCSD
    La Jolla California 92037 United States
  • UCLA Medicine Division of Hematology-Oncology
    Los Angeles California 90095 United States


not yet accepting patients
Start Date
Completion Date
Replimune Inc.
Phase 2 research study
Study Type
Expecting 130 study participants
Last Updated