Study of RP3 in Combination With Nivolumab and Other Therapy in Patients With Locoregionally Advanced or Recurrent SCCHN

NCT ID: NCT05743270

Last Updated: 2025-03-11

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-30
• Study Completion Date: 2026-06-01

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

Conditions

Squamous Cell Carcinoma of Head and Neck; Locally Advanced Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Squamous Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LA Cohort: RP3 in combination with CCRT followed by nivolumab in Locally Advanced SCCHN

RP3 will be administered via direct intratumoral injection or via CT, ultrasound, or laryngoscopy guided intratumoral injection into superficial, subcutaneous (SC), or nodal lesions and into deeper lesions, including visceral lesions.

Group Type: EXPERIMENTAL

RP3

Intervention Type: BIOLOGICAL

Genetically modified herpes simplex type 1 virus

CCRT(concurrent chemoradiation therapy)

Intervention Type: OTHER

CCRT consisting of intensity modulated radiation therapy combined with a cis-platinum

nivolumab

Intervention Type: BIOLOGICAL

anti-PD1 monoclonal antibody

LA Cohort: concurrent chemoradiation therapy in Patients With Locoregionally Advanced SCCHN

standard-of-care CCRT (defined as intensity-modulated radiation therapy \[IMRT\] and cisplatin

Group Type: ACTIVE_COMPARATOR

CCRT(concurrent chemoradiation therapy)

Intervention Type: OTHER

CCRT consisting of intensity modulated radiation therapy combined with a cis-platinum

R/M Cohort:RP3 in combination with carboplatin, paclitaxel and then nivolumab in R/M SCCHN

RP3 will be administered via direct intratumoral injection or via CT, ultrasound, or laryngoscopy guided intratumoral injection into superficial, subcutaneous (SC), or nodal lesions and into deeper lesions, including visceral lesions.

Group Type: EXPERIMENTAL

RP3

Intervention Type: BIOLOGICAL

Genetically modified herpes simplex type 1 virus

carboplatin and paclitaxel

Intervention Type: OTHER

chemotherapeutic agents

nivolumab

Intervention Type: BIOLOGICAL

anti-PD1 monoclonal antibody

Interventions

RP3

Genetically modified herpes simplex type 1 virus

Intervention Type: BIOLOGICAL

CCRT(concurrent chemoradiation therapy)

CCRT consisting of intensity modulated radiation therapy combined with a cis-platinum

Intervention Type: OTHER

carboplatin and paclitaxel

chemotherapeutic agents

Intervention Type: OTHER

nivolumab

anti-PD1 monoclonal antibody

Intervention Type: BIOLOGICAL

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Replimune Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Cohan, MD/FACS

Role: STUDY_DIRECTOR

Replimune Inc.

Locations

University of California San Diego, UCSD

La Jolla, California, United States

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

UCLA Medicine Division of Hematology-Oncology

Los Angeles, California, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Thomas Jefferson University City Center and Abington

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center, UPMC

Pittsburgh, Pennsylvania, United States

Jefferson Health Abington Asplunhd Cancer Pavillion

Willow Grove, Pennsylvania, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

University of Washington / Fred Hutchinson Cancer Center

Seattle, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

University Hospital Olomouc

Olomouc, , Czechia

FN Kralovske Vinohrady

Prague, , Czechia

Fakultni Thomayerova Nemocnice

Prague, , Czechia

Centre Georges Francois Leclerc, Department of Oncology

Dijon, , France

Centre Leon Berard

Lyon, , France

Assistance Publique Hopitaux De Marseille

Marseille, , France

CHU Nimes, Instiut de Cancerologie du Gard, Medical Oncology

Nîmes, , France

Institut Gustave Roussy Paris

Villejuif, , France

Charite University Hospital of Berlin, Comprehensive Cancer Center

Berlin, , Germany

Universitatsklinik Jena Klinik und Poliklinik fur Hals-, Nasen - und Ohrenheilkunde

Jena, , Germany

University Hospital Leipzig Clinic and Polyclinic for otorhinolaryngology

Leipzig, , Germany

LMU Klinikum, Medizinische Klinik und Poliklinikum III

Munich, , Germany

Universitatsklinikum Ulm

Ulm, , Germany

University General Hospital Attikon

Chaïdári, , Greece

Agios Lukas Hospital

Thessaloniki, , Greece

Szpital Specjalistyczny im Ludwika Rydygiera w Krakowie sp z oo, Department of Clinical Oncology

Krakow, , Poland

Vall d'Hebron University Hospital, Vall d' Hebron Institute of Oncology (VHIO)

Barcelona, , Spain

La Paz Univeristy Hospital, Universidad Autonoma de Madrid

Madrid, , Spain

Hospital Universitario HM Sanchinarro

Madrid, , Spain

Clinica Universitaria de Navarra

Pamplona, , Spain

Fundacion Instituto Valenciano de Oncologia

Valencia, , Spain

The Royal Marsden NHS Foundation Trust

London, , United Kingdom

Countries

United States; Czechia; France; Germany; Greece; Poland; Spain; United Kingdom

Other Identifiers

RP3-002

Identifier Type: -

Identifier Source: org_study_id