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

Squamous Cell Carcinoma of Head and Neck Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05743270
• Other study ID #: RP3-002
• Status: Withdrawn
• Phase: Phase 2
• Start date: January 30, 2024
• Est. completion date: June 1, 2026

Study information

• Verified date: December 2023
• Source: Replimune Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 1, 2026
• Est. primary completion date: March 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Locally Advanced Head and Neck Squamous Cell Carcinoma
• Recurrence
• Recurrent Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Biological:
• RP3
Genetically modified herpes simplex type 1 virus

Other:
• CCRT(concurrent chemoradiation therapy)
CCRT consisting of intensity modulated radiation therapy combined with a cis-platinum
• carboplatin and paclitaxel
chemotherapeutic agents

Biological:
• nivolumab
anti-PD1 monoclonal antibody

Locations

Country	Name	City	State
Czechia	University Hospital Olomouc	Olomouc
Czechia	Fakultni Thomayerova Nemocnice	Prague
Czechia	FN Kralovske Vinohrady	Praha
France	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
Germany	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
Greece	University General Hospital Attikon	Chaïdári
Greece	Agios Lukas Hospital	Thessaloníki
Poland	Szpital Specjalistyczny im Ludwika Rydygiera w Krakowie sp z oo, Department of Clinical Oncology	Kraków
Spain	Vall d'Hebron University Hospital, Vall d' Hebron Institute of Oncology (VHIO)	Barcelona
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	La Paz Univeristy Hospital, Universidad Autonoma de Madrid	Madrid
Spain	Clinica Universitaria de Navarra	Pamplona
Spain	Fundacion Instituto Valenciano de Oncologia	Valencia
United Kingdom	The Royal Marsden NHS Foundation Trust	London
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of California San Diego, UCSD	La Jolla	California
United States	UCLA Medicine Division of Hematology-Oncology	Los Angeles	California
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Thomas Jefferson University City Center and Abington	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center, UPMC	Pittsburgh	Pennsylvania
United States	University of Washington / Fred Hutchinson Cancer Center	Seattle	Washington
United States	Jefferson Health Abington Asplunhd Cancer Pavillion	Willow Grove	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Replimune Inc.	Bristol-Myers Squibb

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	LA Cohort: Progression-free Survival Rates at 6 and 12 Months	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 12 months)
Secondary	LA Cohort: Overall Survival Rate at 1, 2, and 3 Years	Overall survival is defined as the time from the first day of study treatment to the date of death by any cause	From Day 1 to date of death by any cause (up to 3 years)
Secondary	LA Cohort: Overall Response Rate and Metabolic Overall Response Rate	Overall Response Rate is the percentage of subjects achieving objective response (complete response + partial response) Metabolic overall response rate is the percentage of subjects achieving objective metabolic response (complete metabolic response + partial metabolic response)	From Day 1 to documented progression of disease (up to 3 years)
Secondary	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	Complete response rate is the percentage of subjects achieving complete response; Metabolic complete response rate is the percentage of subjects achieving metabolic complete response	From Day 1 to documented progression of disease (up to 8Months Following of Initiation of Radiation)
Secondary	LA Cohort: Proportion of Patients Achieving No-Evidence-of-Disease Status by Any Means (Including Salvage Surgery)	No-evidence-of-disease is defined as no evidence of malignancy at any site	From Day 1 to end of study (up to 3 years)
Secondary	LA Cohort: Cumulative Incidence of Locoregional Failure	Locoregional Failure is defined as tumor growth or disease infiltration or spread at the primary tumor location and/or at anatomic areas of local and/or regional disease.	From Day 1 to end of study (up to 3 years)
Secondary	LA Cohort: Cumulative Incidence of Distant Metastatic Failure	Distant metastatic failure is defined as growth of metastases or new appearance of metastases in lung, bone, liver, other distant organs, and/or distant lymph node stations.	From Day 1 to end of study (up to 3 years)
Secondary	LA Cohort: Duration of Clinical Benefit	Duration of clinical benefit is defined as the time from the first day of study treatment to last progression of disease, which was subsequently confirmed or with no further follow-up for response, or death due to any cause, whichever occurs first, for subjects who achieve complete response, partial response, or stable disease	From Day 1 to documented progression of disease (up to 3 years)
Secondary	LA Cohort: Summary of Patient-Reported Outcomes Measured by FACT-HNSI-22	FACT-HNSI-22 is a Functional Assessment of Cancer Therapy Head & Neck Cancer Symptom Index which consists of 22 items. Each item is scored in a 5 point Likert-type scale: 0=Not at all, 1=A little bit, 2=Some-what, 3=Quite a bit, and 4=Very much. The higher the score, the worse the patient outcome.	From Day 1 to 52 Weeks.
Secondary	LA Cohort: Summary of Patient-Reported Outcomes Measured by EQ-5D-5L	EQ-5D-5L is a self-assessed, health related, quality of life questionnaire which consists of 2 pages: EQ-5D descriptive system and EQ visual analogue scale (EQ VAS). The EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale which is numbered from 0 to 100. 0 means the worst health the patient can imagine. 100 means the best health the patient can imagine. The higher the score, the better the patient outcome.	From Day 1 to 52 Weeks
Secondary	LA Cohort: Frequency, Nature, and Severity of TEAEs and SAEs	Percentage of subjects with TEAEs and SAEs	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
Secondary	R/M 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)
Secondary	R/M Cohort: Progression-free Survival Rates at 6 and 12 Months	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 12 months)
Secondary	R/M Cohort: Overall Survival Rates at 1, 2, and 3 Years	Overall survival is defined as the time from the first day of study treatment to the date of death by any cause	From Day 1 to date of death by any cause (up to 3 years)
Secondary	R/M Cohort: Duration of Response	Duration of response is defined as the time from documented response until the date of progression of disease, which was subsequently confirmed or with no further follow-up, or death due to any cause, whichever occurs first	From Day 1 to documented progression of disease (up to 3 years)
Secondary	R/M Cohort: Duration of Clinical Benefit	Duration of clinical benefit is defined as the time from the first day of study treatment to last progression of disease, which was subsequently confirmed or with no further follow-up for response, or death due to any cause, whichever occurs first, for subjects who achieve complete response, partial response, or stable disease	From Day 1 to documented progression of disease (up to 3 years)
Secondary	R/M Cohort: Complete Response Rate	Percentage of subjects achieving a complete response	From Day 1 to documented progression of disease (up to 3 years)
Secondary	R/M Cohort: Disease Control Rate	Percentage of patients achieving complete response, partial response, or stable disease	From Day 1 to documented progression of disease (up to 3 years)
Secondary	R/M Cohort: Number of Patients Who Undergo Attempted Definitive Resection	Number of Patients Who Undergo Attempted Definitive Resection	From Day 1 to end of study (up to 3 years)
Secondary	R/M Cohort: Frequency, Nature, and Severity of TEAEs and SAEs	Percentage of subjects with TEAEs and SAEs	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