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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Patients with advanced or metastatic non-neurological solid tumors, who have progressed on standard therapy or cannot tolerate standard therapy, or for whom there is no standard therapy preferred to enrollment in a clinical study
* All patients must consent to provide archival tumor biopsy samples within 12 months, or a fresh tumor biopsy is needed. Patients must also consent to provide on treatment biopsies as per protocol
* At least one measurable tumor ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes)
* At least one injectable tumor ≥ 1 cm in longest diameter or injectable tumors which in aggregate are ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes
* Have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Note: Predefined inclusion criteria may apply for each additional expansion cohort.
Exclusion Criteria:
* Prior treatment with an oncolytic virus therapy
* History of viral infections according to the protocol
* Systemic infection requiring intravenous (IV) antibiotics
* Active significant herpetic infections or prior complications of HSV-1 infection (e.g., herpetic keratitis or encephalitis)
* Requires intermittent or chronic use of systemic antivirals
a. Hepatocellular carcinoma patients with a diagnosis of hepatitis B must be off antiviral therapy for at least 4 weeks prior to enrollment . Hepatocellular carcinoma patients with a history of or ongoing hepatitis C infection must have completed treatment for hepatitis C at least 1 month prior to study enrollment and hepatitis
* History of interstitial lung disease
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
Additional Exclusion Criteria for Patients Enrolled in Part 2 (Expansion Cohorts):
* 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
* Treatment with botanical preparations within 2 weeks prior to treatment.
* Active, known, or suspected autoimmune disease requiring systemic treatment.
* History of interstitial lung disease.
* Severe hypersensitivity to another monoclonal antibody.
* Has received prior radiotherapy within 2 weeks of start of study treatment.
* Has received a live vaccine within 28 days prior to the first dose of study treatment.
* History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
* History of myocarditis or congestive heart failure within 6 months of screening.
* Has a serious or uncontrolled medical disorder.
* Has a QT interval corrected for heart rate using Fridericia's formula (QTcF) \> 480 msec, except for right bundle branch block.
Primary outcome measure(s)
Incidence of dose limiting toxicities (DLTs) during the DLT period — From Day 1 up to 30 days after last dose Percentage of participants with DLTs
Incidence and severity of treatment emergent adverse events (TEAEs) — From Day 1 up to 60 days after last dose Percentage of participants with TEAEs
Incidence and severity of serious adverse events (SAEs) — From Day 1 up to 60 days after last dose Percentage of participants with SAEs
Incidence of TEAEs ≥ Grade 3 — From Day 1 up to 60 days after last dose Percentage of participants with TEAEs ≥ Grade 3
Percentage of events requiring withdrawal — From Day 1 up to last dose (up to 8 weeks in escalation phase and up to 2 years in combination phase) Percentage of participants experiencing events requiring withdrawal from treatment.
Recommended phase 2 dose (RP2D) of RP3 — 7 months RP2D of RP3 based on the safety and response data collected during the dose escalation phase (Part 1)
Trial sites (13)
Facility
City
Region
Status
University of Iowa
Iowa City
Iowa
UPMC Hillman Cancer Center
Pittsburgh
Pennsylvania
MD Anderson Cancer Center
Houston
Texas
Laboratoire de Recherche Translationnelle en Immunotherapie (LRTI), Gustave Roussy
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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