RP2-001-18 is a Phase 1, multicenter, open label, single agent dose escalation and combination treatment study of RP2 in adult subjects with advanced solid tumors, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), as well as to evaluate preliminary efficacy.
RP2 is a genetically modified herpes simplex type 1 virus (HSV-1) that expresses an anti-CTLA-4 antibody and is designed to directly destroy tumors and to generate an anti-tumor immune response. This is a Phase 1, multicenter, open label, dose escalation and expansion, first-in-human (FIH) clinical study to evaluate the safety and tolerability, biodistribution, shedding, and preliminary efficacy of RP2 alone and in combination with nivolumab in adult subjects with advanced solid tumors. The study will be conducted in two parts. The first part of the study is an open-label, dose escalation FIH Phase 1 study to assess the safety and tolerability of RP2 and to determine the recommended Phase 2 dose (RP2D) to be used in the second part of the study. The second part of the study is an open label design to further investigate safety of RP2 in combination with nivolumab. It will also assess the biological activity of multiple doses of RP2 in combination with nivolumab. An expansion to the second part of the study will include enrolment of a further 30 patients on RP2 in combination with nivolumab. Following completion of the expansion in part 2, part 3 will enroll a further 15 patients on RP3 monotherapy. The expansion to part 2 and part 3 will focus on patients with advanced or metastatic uveal melanoma, lung cancer, breast cancer or GI cancers and patients with liver metastasis.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Hospital Universitario d'Hebron
Barcelona, Spain
Hospital Universitario HM Sanchinarro
Madrid, Spain
Hospital Clinico de Valencia
Valencia, Spain
The Clatterbridge Cancer Centre NHS Foundation Trust
Bebington, Merseyside, United Kingdom
Percentage of adverse events (AEs)
Percentage of subjects with AEs
Time frame: From Day 1 up to 60 days after last dose
Percentage of serious adverse events (SAEs)
Percentage of subjects with SAEs
Time frame: From Day 1 up to 60 days after last dose
Percentage of dose limiting toxicities (DLTs)
Percentage of subjects with DLTs
Time frame: From Day 1 up to 30 days after last dose.
Percentage of treatment emergent adverse events (TEAEs)
Percentage of subjects with TEAEs
Time frame: From Day 1 up to 60 days after last dose.
Percentage of TEAEs ≥ Grade 3
Percentage of subjects with TEAEs ≥ Grade 3
Time frame: From Day 1 up to 60 days after last dose.
Percentage of events requiring withdrawal
Percentage of subjects experiencing events requiring withdrawal from treatment.
Time frame: From Day 1 up to last dose (up to 8 weeks for dose escalation phase and up to 2 years for expansion phase)).
Maximum tolerated dose (MTD) of RP2
MTD on the safety and response data collected during the dose escalation phase (Part 1).
Time frame: 7 months
Recommended Phase 2 dose (RP2D) of RP2
RP2D of RP2 based on the safety and response data collected during the dose escalation phase (Part 1).
Time frame: 7 months
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The Royal Marsden NHS Foundation Trust
London, United Kingdom
Churchill Hospital
Oxford, United Kingdom
Percentage of biologic activity
Percentage of subjects with biological activity determined by tumor biopsies and biomarker data
Time frame: 20 weeks
Percentage of subjects with detectable RP2
Data gathered from blood, urine, swabs of injection site, dressings, and oral mucosa to determine the shedding and biodistribution of RP2.
Time frame: 20 weeks
Change in HSV-1 antibody levels
Change in HSV-1 antibody levels during treatment compared to baseline
Time frame: From Day 1 up to last dose (up to 4 months for dose escalation phase and up to 5.5 months for expansion phase)).
Percentage of overall response rate (ORR)
Percentage of ORR.
Time frame: 3 years
Median duration of response
Median duration of response of subjects
Time frame: 3 years
Median progression-free survival
Median duration of progression-free survival of subjects
Time frame: 3 years
Median overall survival
Median overall survival rate of subjects
Time frame: 3 years
Percentage of complete response (CR)
Percentage of subjects with a CR
Time frame: From Day 1 up to last dose (up to 8 weeks for escalation phase and up to 2 years for expansion phase).
Percentage of partial response (PR)
Percentage of subjects with a PR
Time frame: From Day 1 up to last dose (up to 8 weeks for escalation phase and up to 2 years for expansion phase).
Percentage of stable disease (SD)
Percentage of subjects with SD
Time frame: From Day 1 up to last dose (up to 8 weeks for escalation phase and up to 2 years for expansion phase).