Clinical trial NCT05743270: Study of RP3 in Combination With Nivolumab and Other Therapy in Patients With Locoregionally Advanced or Recurrent SCCHN
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Squamous Cell Carcinoma of Head and Neck
Locally Advanced Head and Neck Squamous Cell Carcinoma
Recurrent Head and Neck Squamous Cell Carcinoma
Keywords: Squamous cell carcinomas of head and neck
Immunotherapy
Immuno-oncology
Oncolytic virus
Oncolytic immuno-gene therapy
Lead sponsor: Replimune Inc.
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2023-02-24
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: LA Cohort: Progression-free Survival
timeFrame: From Day 1 to documented progression of disease (up to 3 years)
measure: R/M Cohort: Objective Response Rate
timeFrame: From Day 1 to documented progression of disease (up to 3 years)
Secondary outcomes:
measure: LA Cohort: Progression-free Survival Rates at 6 and 12 Months
timeFrame: From Day 1 to documented progression of disease (up to 12 months)
measure: LA Cohort: Overall Survival Rate at 1, 2, and 3 Years
timeFrame: From Day 1 to date of death by any cause (up to 3 years)
measure: LA Cohort: Overall Response Rate and Metabolic Overall Response Rate
timeFrame: From Day 1 to documented progression of disease (up to 3 years)
measure: LA Cohort: Complete Response Rate and Metabolic Complete Response Rate at 5-and 8-months Following of Initiation of Radiation Following of Initiation of Radiation
timeFrame: From Day 1 to documented progression of disease (up to 8Months Following of Initiation of Radiation)
measure: LA Cohort: Proportion of Patients Achieving No-Evidence-of-Disease Status by Any Means (Including Salvage Surgery)
timeFrame: From Day 1 to end of study (up to 3 years)
measure: LA Cohort: Cumulative Incidence of Locoregional Failure
timeFrame: From Day 1 to end of study (up to 3 years)
measure: LA Cohort: Cumulative Incidence of Distant Metastatic Failure
timeFrame: From Day 1 to end of study (up to 3 years)
measure: LA Cohort: Duration of Clinical Benefit
timeFrame: From Day 1 to documented progression of disease (up to 3 years)
measure: LA Cohort: Summary of Patient-Reported Outcomes Measured by FACT-HNSI-22
timeFrame: From Day 1 to 52 Weeks.
measure: LA Cohort: Summary of Patient-Reported Outcomes Measured by EQ-5D-5L
timeFrame: From Day 1 to 52 Weeks
measure: LA Cohort: Frequency, Nature, and Severity of TEAEs and SAEs
timeFrame: From Screening through 60 days after last dose of RP3, or 100 days after last dose of nivolumab, or 28 days after last dose of either cisplatin, carboplatin, or paclitaxel, whichever occurs last
measure: R/M Cohort: Progression-free Survival
timeFrame: From Day 1 to documented progression of disease (up to 3 years)
measure: R/M Cohort: Progression-free Survival Rates at 6 and 12 Months
timeFrame: From Day 1 to documented progression of disease (up to 12 months)
measure: R/M Cohort: Overall Survival Rates at 1, 2, and 3 Years
timeFrame: From Day 1 to date of death by any cause (up to 3 years)
measure: R/M Cohort: Duration of Response
timeFrame: From Day 1 to documented progression of disease (up to 3 years)
measure: R/M Cohort: Duration of Clinical Benefit
timeFrame: From Day 1 to documented progression of disease (up to 3 years)
measure: R/M Cohort: Complete Response Rate
timeFrame: From Day 1 to documented progression of disease (up to 3 years)
measure: R/M Cohort: Disease Control Rate
timeFrame: From Day 1 to documented progression of disease (up to 3 years)
measure: R/M Cohort: Number of Patients Who Undergo Attempted Definitive Resection
timeFrame: From Day 1 to end of study (up to 3 years)
measure: R/M Cohort: Frequency, Nature, and Severity of TEAEs and SAEs
timeFrame: From Screening through 60 days after last dose of RP3, or 100 days after last dose of nivolumab, or 28 days after last dose of either cisplatin, carboplatin, or paclitaxel, whichever occurs last
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego, UCSD
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA Medicine Division of Hematology-Oncology
state: California
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University City Center and Abington
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center, UPMC
state: Pennsylvania
city: Willow Grove
country: United States
facility: Jefferson Health Abington Asplunhd Cancer Pavillion
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Seattle
country: United States
facility: University of Washington / Fred Hutchinson Cancer Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Olomouc
country: Czechia
facility: University Hospital Olomouc
city: Prague
country: Czechia
facility: Fakultni Thomayerova Nemocnice
city: Praha
country: Czechia
facility: FN Kralovske Vinohrady
city: Dijon
country: France
facility: Centre Georges Francois Leclerc, Department of Oncology
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Assistance Publique Hopitaux De Marseille
city: Nîmes
country: France
facility: CHU Nimes, Instiut de Cancerologie du Gard, Medical Oncology
city: Villejuif
country: France
facility: Institut Gustave Roussy Paris
city: Berlin
country: Germany
facility: Charite University Hospital of Berlin, Comprehensive Cancer Center
city: Jena
country: Germany
facility: Universitatsklinik Jena Klinik und Poliklinik fur Hals-, Nasen - und Ohrenheilkunde
city: Leipzig
country: Germany
facility: University Hospital Leipzig Clinic and Polyclinic for otorhinolaryngology
city: Munich
country: Germany
facility: LMU Klinikum, Medizinische Klinik und Poliklinikum III
city: Ulm
country: Germany
facility: Universitatsklinikum Ulm
city: Chaïdári
country: Greece
facility: University General Hospital Attikon
city: Thessaloníki
country: Greece
facility: Agios Lukas Hospital
city: Kraków
country: Poland
facility: Szpital Specjalistyczny im Ludwika Rydygiera w Krakowie sp z oo, Department of Clinical Oncology
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital, Vall d' Hebron Institute of Oncology (VHIO)
city: Madrid
country: Spain
facility: La Paz Univeristy Hospital, Universidad Autonoma de Madrid
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
city: Valencia
country: Spain
facility: Fundacion Instituto Valenciano de Oncologia
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Replimune Inc.
name: David Cohan, MD/FACS
role: STUDY_DIRECTOR
References: