Study of RP2 Monotherapy and RP2 in Combination With Nivolumab in Patients With Solid Tumors

NCT04336241 | Active Not Recruiting Phase 1

• 1 other identifier: RP2-001-18
• Study Type: interventional
• Target: 36
• Locations: 2 countries
• Sites: 6

Brief Summary

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.

Conditions

Cancer

Keywords

Uveal Melanoma; Gastrointestinal Cancers; Lung Cancer; Breast Cancer

Outcome Measures

Primary Outcomes (8)

• Percentage of adverse events (AEs)

  Percentage of subjects with AEs

  From Day 1 up to 60 days after last dose

• Percentage of serious adverse events (SAEs)

  Percentage of subjects with SAEs

  From Day 1 up to 60 days after last dose

• Percentage of dose limiting toxicities (DLTs)

  Percentage of subjects with DLTs

  From Day 1 up to 30 days after last dose.

• Percentage of treatment emergent adverse events (TEAEs)

  Percentage of subjects with TEAEs

  From Day 1 up to 60 days after last dose.

• Percentage of TEAEs ≥ Grade 3

  Percentage of subjects with TEAEs ≥ Grade 3

  From Day 1 up to 60 days after last dose.

• Percentage of events requiring withdrawal

  Percentage of subjects experiencing events requiring withdrawal from treatment.

  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).

  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).

  7 months

Secondary Outcomes (10)

• Percentage of biologic activity

  20 weeks

• Percentage of subjects with detectable RP2

  20 weeks

• Change in HSV-1 antibody levels

  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)

  3 years

• Median duration of response

  3 years

Study Arms (5)

Dose escalation of RP2 - superficial tumors

EXPERIMENTAL

Dose escalation of RP2 alone in 3 cohorts with IT injections in superficial tumors.

Biological: RP2

Dose escalation of RP2 - deep/visceral tumors

EXPERIMENTAL

Dose escalation of RP2 alone in 3 cohorts with imaging guided IT injections in deep/visceral tumors.

Biological: RP2

Dose expansion of RP2 and nivolumab - superficial tumors

EXPERIMENTAL

Doses of RP2 (IT) in superficial tumors with nivolumab (IV).

Biological: RP2; Biological: nivolumab

Dose expansion of RP2 and nivolumab - deep/visceral tumors

EXPERIMENTAL

Imaging guided doses of RP2 (IT) in deep/visceral tumors.

Biological: RP2; Biological: nivolumab

Seronegative cohort

EXPERIMENTAL

Doses of RP2 (IT) in HSV seronegative participants.

Biological: RP2

Interventions

RP2 BIOLOGICAL

Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation

Dose escalation of RP2 - deep/visceral tumors; Dose escalation of RP2 - superficial tumors; Dose expansion of RP2 and nivolumab - deep/visceral tumors; Dose expansion of RP2 and nivolumab - superficial tumors; Seronegative cohort

nivolumab BIOLOGICAL

Programmed death receptor (PD-1) blocking antibody

Also known as: Opdivo

Dose expansion of RP2 and nivolumab - deep/visceral tumors; Dose expansion of RP2 and nivolumab - superficial tumors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to participate and comply with all trial requirements and able to provide signed and dated informed consent prior to initiation of any trial procedures
• Male or Female ≥ 18 years of age
• Patients with advanced or metastatic non-neurological solid tumors, who have progressed on standard therapy or cannot tolerate standard therapy, or for which there is no standard therapy preferred to enrolment in a clinical trial
• Consent to provide archival tumour biopsy samples within 6 months, or a fresh tumour biopsy is needed. Patients must also consent to provide on-treatment biopsies as per protocol
• At least one measurable and injectable tumor of ≥ 1 cm in longest diameter (or shorter diameter for lymph nodes).
• Women of child-bearing potential (WOCBP) must have a negative urine pregnancy test at screening and a negative urine pregnancy test prior to administration of each dose of RP2 or nivolumab
• WOCBP must agree to use adequate birth control throughout their participation and for 3 months after RP2 alone and 5 months after nivolumab last study treatment
• Males with partners of child-bearing potential must agree to use adequate birth control throughout their participation and for 3 months for RP2 alone and 7 months after nivolumab last study treatment
• Have laboratory values (obtained ≤ 28 days prior to first infusion day) in accordance with the study protocol
• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• Cohort 2a only:
• Baseline ECG that does not show abnormalities according to the protocol
• Baseline troponin \< 0.06 ng/mL
• Baseline oxygen saturation levels that do not show abnormalities according to the protocol
• Cohort 2b and Part 3 only:

You may not qualify if:

• Prior treatment with an oncolytic virus therapy
• History of viral infections according to the protocol
• Systemic infection requiring IV antibiotics within 14 days prior to dosing
• Prior complications with herpes infections
• Chronic use of anti-virals
• Systemic therapies for cancer within five half-lives or 4 weeks of first dose; whichever is shorter
• Conditions that require certain doses of steroids (some doses and types will be permitted)
• Known active brain metastases - previously treated brain metastases may be permitted
• Major surgery ≤ 2 weeks prior to starting study drug
• Prior malignancy active with the previous 3 years; except for locally curable cancers that have apparently been cured
• Female who has a positive urine pregnancy test or is breast-feeding or planning to become pregnant during study treatment and 90 days for RP2 alone or 5 months for RP2 and nivolumab after the last dose of treatment
• Participation in another clinical study within 4 weeks prior to the first dose
• History of myocarditis or congestive heart failure (as defined by the New York Heart Association Functional Classification III or IV), or unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction within 6 months of randomization
• History of allergy or sensitivity to study drug components
• Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study

Sponsors & Collaborators

• Replimune Inc.: lead

Study Sites (6)

Hospital Universitario d'Hebron

Barcelona, 119 08035, Spain

Location

Hospital Universitario HM Sanchinarro

Madrid, 10 28050, Spain

Location

Hospital Clinico de Valencia

Valencia, 46010, Spain

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, Merseyside, CH63 4JY, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

Churchill Hospital

Oxford, OX3 9DU, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms; Uveal Melanoma; Gastrointestinal Neoplasms; Lung Neoplasms; Breast Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Gary Vanasse, MD

  Replimune Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 - Dose Escalation - Patients will be enrolled into three sequential dose level cohorts. Part 2 - Dose expansion - Patients will receive a fixed dose of RP2 in combination with Nivolumab. Part 3 - Patients will receive four doses of RP2 monotherapy

Study Record Dates

• First Submitted: March 17, 2020
• First Posted: April 7, 2020
• Study Start: October 17, 2019
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

GB (3); ES (3)