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

NCT05743270 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: RP3-002
• Study Type: interventional
• Target: N/A
• Locations: 8 countries
• Sites: 34

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.

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

Outcome Measures

Primary Outcomes (2)

• LA Cohort: Progression-free Survival

  Progression-free survival is defined as the time from the first day of study treatment to the date of progression of disease, which was subsequently confirmed, or death by any cause, whichever occurs first

  From Day 1 to documented progression of disease (up to 3 years)

• R/M Cohort: Objective Response Rate

  Percentage of subjects achieving objective response (complete response + partial response)

  From Day 1 to documented progression of disease (up to 3 years)

Secondary Outcomes (20)

• LA Cohort: Progression-free Survival Rates at 6 and 12 Months

  From Day 1 to documented progression of disease (up to 12 months)

• LA Cohort: Overall Survival Rate at 1, 2, and 3 Years

  From Day 1 to date of death by any cause (up to 3 years)

• LA Cohort: Overall Response Rate and Metabolic Overall Response Rate

  From Day 1 to documented progression of disease (up to 3 years)

• 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

  From Day 1 to documented progression of disease (up to 8Months Following of Initiation of Radiation)

• LA Cohort: Proportion of Patients Achieving No-Evidence-of-Disease Status by Any Means (Including Salvage Surgery)

  From Day 1 to end of study (up to 3 years)

Study Arms (3)

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

EXPERIMENTAL

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.

Biological: RP3; Other: CCRT(concurrent chemoradiation therapy); Biological: nivolumab

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

ACTIVE COMPARATOR

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

Other: CCRT(concurrent chemoradiation therapy)

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

EXPERIMENTAL

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.

Biological: RP3; Other: carboplatin and paclitaxel; Biological: nivolumab

Interventions

RP3 BIOLOGICAL

Genetically modified herpes simplex type 1 virus

LA Cohort: RP3 in combination with CCRT followed by nivolumab in Locally Advanced SCCHN; R/M Cohort:RP3 in combination with carboplatin, paclitaxel and then nivolumab in R/M SCCHN

CCRT(concurrent chemoradiation therapy) OTHER

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

LA Cohort: RP3 in combination with CCRT followed by nivolumab in Locally Advanced SCCHN; LA Cohort: concurrent chemoradiation therapy in Patients With Locoregionally Advanced SCCHN

carboplatin and paclitaxel OTHER

chemotherapeutic agents

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

nivolumab BIOLOGICAL

anti-PD1 monoclonal antibody

LA Cohort: RP3 in combination with CCRT followed by nivolumab in Locally Advanced SCCHN; R/M Cohort:RP3 in combination with carboplatin, paclitaxel and then nivolumab in R/M SCCHN

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify 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.

Sponsors & Collaborators

• Replimune Inc.: lead
• Bristol-Myers Squibb: collaborator

Study Sites (34)

University of California San Diego, UCSD

La Jolla, California, 92037, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

UCLA Medicine Division of Hematology-Oncology

Los Angeles, California, 90095, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Thomas Jefferson University City Center and Abington

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Medical Center, UPMC

Pittsburgh, Pennsylvania, 15232, United States

Location

Jefferson Health Abington Asplunhd Cancer Pavillion

Willow Grove, Pennsylvania, 19090, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

University of Washington / Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

University Hospital Olomouc

Olomouc, 779 00, Czechia

Location

FN Kralovske Vinohrady

Prague, 100 00, Czechia

Location

Fakultni Thomayerova Nemocnice

Prague, 140 59, Czechia

Location

Centre Georges Francois Leclerc, Department of Oncology

Dijon, 21079, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

Assistance Publique Hopitaux De Marseille

Marseille, 13005, France

Location

CHU Nimes, Instiut de Cancerologie du Gard, Medical Oncology

Nîmes, 30029, France

Location

Institut Gustave Roussy Paris

Villejuif, 94805, France

Location

Charite University Hospital of Berlin, Comprehensive Cancer Center

Berlin, 12203, Germany

Location

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

Jena, 07747, Germany

Location

University Hospital Leipzig Clinic and Polyclinic for otorhinolaryngology

Leipzig, 04103, Germany

Location

LMU Klinikum, Medizinische Klinik und Poliklinikum III

Munich, 81377, Germany

Location

Universitatsklinikum Ulm

Ulm, 89075, Germany

Location

University General Hospital Attikon

Chaïdári, 12462, Greece

Location

Agios Lukas Hospital

Thessaloniki, 55236, Greece

Location

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

Krakow, 31-826, Poland

Location

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

Barcelona, 08035, Spain

Location

La Paz Univeristy Hospital, Universidad Autonoma de Madrid

Madrid, 28046, Spain

Location

Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

Location

Clinica Universitaria de Navarra

Pamplona, 31008, Spain

Location

Fundacion Instituto Valenciano de Oncologia

Valencia, 46009, Spain

Location

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Carboplatin; Paclitaxel; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• David Cohan, MD/FACS

  Replimune Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2023
• First Posted: February 24, 2023
• Study Start: January 30, 2024
• Primary Completion: March 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: March 11, 2025

Record last verified: 2025-03

Locations

ES (5); DE (5); GR (2); PL (1); US (12); CZ (3); FR (5); GB (1)