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.
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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Genetically modified herpes simplex type 1 virus
CCRT consisting of intensity modulated radiation therapy combined with a cis-platinum
chemotherapeutic agents
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
Time frame: 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)
Time frame: From Day 1 to documented progression of disease (up to 3 years)
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
Time frame: From Day 1 to documented progression of disease (up to 12 months)
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
Time frame: From Day 1 to date of death by any cause (up to 3 years)
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)
Time frame: 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
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anti-PD1 monoclonal antibody
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
...and 24 more locations
Complete response rate is the percentage of subjects achieving complete response Metabolic complete response rate is the percentage of subjects achieving metabolic complete response
Time frame: 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)
No-evidence-of-disease is defined as no evidence of malignancy at any site
Time frame: From Day 1 to end of study (up to 3 years)
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.
Time frame: From Day 1 to end of study (up to 3 years)
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.
Time frame: From Day 1 to end of study (up to 3 years)
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
Time frame: From Day 1 to documented progression of disease (up to 3 years)
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.
Time frame: From Day 1 to 52 Weeks.
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.
Time frame: From Day 1 to 52 Weeks
LA Cohort: Frequency, Nature, and Severity of TEAEs and SAEs
Percentage of subjects with TEAEs and SAEs
Time frame: 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
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
Time frame: From Day 1 to documented progression of disease (up to 3 years)
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
Time frame: From Day 1 to documented progression of disease (up to 12 months)
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
Time frame: From Day 1 to date of death by any cause (up to 3 years)
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
Time frame: From Day 1 to documented progression of disease (up to 3 years)
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
Time frame: From Day 1 to documented progression of disease (up to 3 years)
R/M Cohort: Complete Response Rate
Percentage of subjects achieving a complete response
Time frame: From Day 1 to documented progression of disease (up to 3 years)
R/M Cohort: Disease Control Rate
Percentage of patients achieving complete response, partial response, or stable disease
Time frame: From Day 1 to documented progression of disease (up to 3 years)
R/M Cohort: Number of Patients Who Undergo Attempted Definitive Resection
Number of Patients Who Undergo Attempted Definitive Resection
Time frame: From Day 1 to end of study (up to 3 years)
R/M Cohort: Frequency, Nature, and Severity of TEAEs and SAEs
Percentage of subjects with TEAEs and SAEs
Time frame: 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