This is a Phase 1, multicenter, open label, single agent dose escalation and combination treatment study of RP3 in adult participants with advanced solid tumors, to evaluate the safety and tolerability of RP3 both as a single agent and in combination with anti-PD1 therapy and to determine the recommended Phase 2 dose (RP2D) of RP3.
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 destroy tumors and generate an anti-tumor immune response
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
123
University of Iowa
Iowa City, Iowa, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States
MD Anderson Cancer Center
Houston, Texas, United States
Incidence of dose limiting toxicities (DLTs) during the DLT period
Percentage of participants with DLTs
Time frame: From Day 1 up to 30 days after last dose
Incidence and severity of treatment emergent adverse events (TEAEs)
Percentage of participants with TEAEs
Time frame: From Day 1 up to 60 days after last dose
Incidence and severity of serious adverse events (SAEs)
Percentage of participants with SAEs
Time frame: From Day 1 up to 60 days after last dose
Incidence of TEAEs ≥ Grade 3
Percentage of participants with TEAEs ≥ Grade 3
Time frame: From Day 1 up to 60 days after last dose
Percentage of events requiring withdrawal
Percentage of participants experiencing events requiring withdrawal from treatment.
Time frame: From Day 1 up to last dose (up to 8 weeks in escalation phase and up to 2 years in combination phase)
Recommended phase 2 dose (RP2D) of RP3
RP2D of RP3 based on the safety and response data collected during the dose escalation phase (Part 1)
Time frame: 7 months
Percentage of biologic activity
Percentage of participants with biological activity as assessed by individual tumor responses (including erythema, necrosis, and/or inflammation and changes in tumor sizes, in injected and uninjected tumors).
Time frame: From Day 1 to 24 months following the last dose in dose escalation. From Day 1 to 100 days following the last dose in dose combination
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Laboratoire de Recherche Translationnelle en Immunotherapie (LRTI), Gustave Roussy
Villejuif, France
University of Athens
Athens, Greece
University General Hospital Attikon
Athens, Greece
Vall d'Hebron Hospital Hospital Universitario Vall d´Hebron (Vall d'Hebron University Hospital)
Barcelona, Spain
Hospital Clinic Barcelona
Barcelona, Spain
START Madrid CIO Clara Campal, Hospital Universitario HM Sanchinarro Unidad de Ensayos Fase I Panta 3
Madrid, Spain
Hospital Clinico Universitario de Valencia
Valencia, Spain
...and 3 more locations
Incidence of clearance of RP3 from blood and urine
Incidence of clearance of RP3 from blood and urine before and after each injection
Time frame: From Day 1 to 60 days following the last dose in dose escalation. From Day 1 to 100 days following the last dose in dose combination
Percentage of participants with detectable RP3.
Data gathered from blood, urine, swabs of injection site, dressing and oral mucosa to determine the shedding and biodistribution of RP3
Time frame: From Day 1 to 60 days following the last dose in dose escalation. From Day 1 to 100 days following the last dose in dose combination
Change in HSV-1 antibody levels
Change in HSV-1 antibody levels during treatment compared to baseline
Time frame: From Day 1 to Day 43
Percentage of HSV-1 seronegative patients with TEAEs
Percentage of HSV-1 seronegative patients with TEAEs
Time frame: From Day 1 to 60 days following last dose in dose escalation. From Day 1 to 100 days post last dose in dose combination
Percentage of objective overall response rate (ORR)
Percentage of ORR
Time frame: Up to 3 years since first patient in
Median duration of response
Median duration of response of participants
Time frame: Up to 3 years since first patient in
Percentage of complete response (CR)
Percentage of participants with a CR
Time frame: From Day 1 up to last dose (Day 57 or 8th Re-initiation dose in escalation phase and up to 2 years for combination phase)
Percentage of partial response (PR)
Percentage of participants with a PR
Time frame: From Day 1 up to last dose (Day 57 or 8th Re-initiation dose in escalation phase and up to 2 years for combination phase)
Percentage of stable disease (SD)
Percentage of participants with SD
Time frame: From Day 1 up to last dose (Day 57 or 8th Re-initiation dose in escalation phase and up to 2 years for combination phase)
Progression-free survival by Investigator review
Length of time during and after treatment, that a patient lives with disease but it does not get worse
Time frame: From Day 1 to day of last follow-up
One-year and 2-year OS rates
Percentage of participants from Day 1 of treatment who reach one year or two year survival
Time frame: From Day 1 to Day 730