Open Menu
Meetings & Education
Meetings & Education
Research & Data
Practice & Patients
Career Development
News & Initiatives
Get Involved
A randomized, phase 2/3 clinical trial investigating RP2 plus nivolumab vs ipilimumab plus nivolumab in immune checkpoint inhibitor-naĂŻve patients with metastatic uveal melanoma.
Background: Uveal melanoma (UM) is the most common primary intraocular malignancy, accounting for nearly 90% of ocular melanomas and up to 5% of melanomas overall. Approximately 50% of patients (pts) with UM will develop metastatic disease, with the liver being the most common site of metastases (~90%). The prognosis for pts with metastatic UM (mUM) is poor, with a median overall survival (OS) of approximately 1 year. Effective treatment options for mUM are limited as it responds poorly to single-agent immune checkpoint inhibitors (ICIs; <10% response rate). Response rates are slightly higher with combination therapies (12%–18%), but often at the expense of increased toxicity. Tebentafusp is FDA approved for mUM based on survival benefit; however, its use is restricted to pts who are HLA-A*02:01 positive, and only ~10% of pts achieve an objective response. RP2 is a selectively replication-competent herpes simplex virus type 1–based oncolytic immunotherapy expressing GM-CSF, a fusogenic glycoprotein (GALV-GP-R–), and an anti–CTLA-4 antibody-like molecule. Prior phase 1 preliminary clinical data of RP2 as monotherapy or in combination with nivolumab (nivo) demonstrated a promising safety profile and anti-tumor activity with an ORR of 29.4% in 17 patients with mUM, most of whom had received prior ICIs. This study will assess the efficacy and safety of RP2 + nivo vs ipilimumab (ipi) + nivo in pts with ICI-naïve mUM (NCT06581406; RP2-202).
Methods: This is a randomized, controlled, phase 2/3 study. Key eligibility criteria include age ≥18 years and confirmed unresectable mUM with lesions amenable to injection. Pts with metastatic disease who have had prior exposure to ICIs since the time of UM diagnosis, involvement of >33.3% of the liver, or a history of prior liver- or lesion-directed therapy are not eligible for enrollment. Enrolled pts (N = ~280) will be randomized 1:1 to receive either RP2 + nivo or ipi + nivo. In the RP2 + nivo arm, RP2 will be given intratumorally initially at 1 x 106 PFU/mL, then every 2 weeks (Q2W) at 1 x 107 PFU/mL for 7 doses in combination with intravenous (IV) nivo (240 mg). In the ipi + nivo arm, pts will receive IV ipi (3 mg/kg) and IV nivo (1 mg/kg) Q3W for 4 doses. Pts in both arms may then receive IV nivo at 240 mg Q2W or 480 mg Q4W for up to 2 years from the first dose. The co-primary endpoints are OS and progression-free survival by independent central review using RECIST 1.1. Secondary endpoints are overall response rate, duration of response, disease control rate, clinical benefit rate, duration of clinical benefit, and safety, including incidence of treatment-emergent adverse events (AEs), serious AEs, and immune-mediated AEs.
Disclaimer
This material on this page is ©2025 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Author Details
Joseph Sacco
The Clatterbridge Cancer Centre and University of Liverpool, Wirral and Liverpool, United Kingdom
Authors chevron_right
Associated Organizations chevron_right
Abstract Details
Meeting
2025 ASCO Annual Meeting
Session Type
Poster Session
Session Title
Melanoma/Skin Cancers
Track
Melanoma/Skin Cancers
View MoreAbstract Disclosure
open_in_new
Your Privacy
ASCO is committed to transparency regarding our websites and the ways we process data. When you visit our site, we may store or retrieve information on your browser, mostly in the form of cookies. This information might be about you, your preferences, your location, or your device and is mostly used to make the site work as you expect it to and to personalize your web experience with us.
Because we respect your right to privacy, you can choose not to allow some or all types of cookies. Click on the different category headings to find out more about the types of cookies used on our websites and change your default settings to match your preferences. Please read these carefully. Blocking some types of cookies may impact your experience on the site, including our ability to personalize the content you receive from us.
For a full explanation of the personal and non-personal information we collect on our site, including how we use that information and your rights regarding that information, please review our Privacy Policy. Use of our website is also subject to our Terms of Use.
Allow All
Manage Consent Preferences
Essential Website Cookies
Always Active
These cookies are necessary for the website to function and are sometimes referred to as “strictly necessary” cookies. They make sure the website delivers you information and services in an optimal way.
They are often set in response to an action you take, such as changing your cookie preferences, setting your privacy preferences, logging in to our website, asking the site to remember you on subsequent pages, or filling in forms. These cookies do not identify you personally.
You can set your browser to block or alert you about all cookies, including essential website cookies, but some parts of the site will not work as a result.
Cookies Details‎
Performance and Functionality Cookies
Performance and Functionality Cookies
These cookies enhance the performance and functionality of our websites and the services we provide. For example, these cookies can keep track of your visitor session in between visits, enable you to share content through social media, use embedded media players, and use comment features. They also help us balance website load and improve site speed and performance.
All information these cookies collect is aggregated and therefore anonymous. These cookies may be set by us or by third party providers whose services we have added to our websites. These cookies are non-essential, but without these cookies, certain functionality or enhanced features may become unavailable.
Cookies Details‎
Personalization and Analytics Cookies
Personalization and Analytics Cookies
These cookies collect information that is used to help us understand how our websites and content are used, help us customize our websites and application for you in order to enhance your experience, and help us improve the content that ASCO creates to better meet our members’ and visitors’ needs. Examples include cookies that show us which content might be most popular with our visitors, understand browsing history of our users, understand the effectiveness of our own advertising, and enable us to recommend content to individual users based on their profile and activities on the website.
These cookies may be set by us or by third party providers whose services we have added to our websites.
These cookies are non-essential to the functionality of the site and may contain information that enables us or our third party providers to identify you and build a profile of your interests. Without these cookies, you will not be able to have a customized or personalized experience within our website.
Cookies Details‎
Advertising Cookies and Social Media Cookies
Advertising Cookies and Social Media Cookies
Advertising (or Targeting) cookies are third party cookies that may be set through our site by our advertising partners. They may be used by those companies to build a profile of your interests and show you relevant ads on other sites.
Social Media Cookies are cookies set by a range of social media services that we have added to the site to enable you to share our content with your friends and networks. They are capable of tracking your activities across other sites and building a profile of your interests. This may impact the content and messages you see on other websites you visit.
These cookies and the data collected by the third parties may be combined with data from other users or data about your activity on other sites. While the data collected on our site is aggregate or non-personal, the data may be used by such third parties to link you on other platforms or otherwise identify you.
If you do not allow these cookies, you may experience less targeted advertising.
Cookies Details‎
Back Button
Cookie List
Search Icon
Filter Icon
Clear
checkbox labellabel
ApplyCancel
ConsentLeg.Interest
checkbox labellabel
checkbox labellabel
checkbox labellabel
View Cookies
Name
cookie name
Save Settings
Download