Open Menu
Meetings & Education
Meetings & Education
Research & Data
Practice & Patients
Career Development
News & Initiatives
Get Involved
The TIME trial: Phase II randomized controlled trial of time-of-day–specified immunotherapy for advanced melanoma.
Background: Ipilimumab + nivolumab is standard of care for advanced melanoma patients based on data from the CheckMate 067 trial. The recent 10-year outcomes results were reported with a melanoma specific survival of 52%. While data are very encouraging, 50% of patients still succumb to their disease by 10-years. Preclinical data suggests that the circadian rhythm may influence the anatomic localization, function and activity of T cells, the target of immunotherapy. More T cells in the tumor or tumor-draining lymph node during initial immunotherapy administration may improve clinical responses and long-term outcomes. To investigate this idea, we performed a retrospective analysis, the MEMOIR study, finding that more evening infusions of immunotherapy were associated with significantly worse progression free and overall survival for metastatic melanoma patients. These findings have now been reproduced in other cancer types, in a large meta-analysis, and in pre-clinical mechanistic studies. In light of these data, we hypothesize that patients receiving morning or midday infusions of immunotherapy will have better outcomes than patients receiving infusions in the evening.
Methods: The TIME trial is a three-arm phase II study of time-of-day specified administration of standard dose ipilimumab + nivolumab for metastatic melanoma. Newly diagnosed unresectable metastatic melanoma patients will be randomized to receive 4 cycles of ipilimumab + nivolumab every 3 weeks between either 8:00-11:00 (Arm A), 11:00-14:00 (Arm B), or 14:00-17:00 (Arm C). Following these 4 cycles, they will receive standard of care maintenance nivolumab in a time-of-day agnostic fashion. Eligible adult patients must have Stage III-IV unresectable cutaneous, acral or mucosal melanoma, no prior immunotherapy within 1 year, ECOG performance status of 0-1, and only asymptomatic brain metastases less than 2 cm. The primary objective is to determine whether progression free survival for Arm A or Arm B is superior to Arm C. Secondary objectives include assessments of adverse events, melanoma specific survival and overall survival. We also plan to evaluate the immune profiles of blood and tumor, when available, to assess the impact of time-of-day administered ipilimumab + nivolumab on the circulating immune responses and the tumor immune microenvironment. A sample size of 99 patients (33 in each arm) was selected for at least 80% power to detect a HR of 0.50 with a Type 1 error rate of 0.1 (2-sided) for a comparison of A vs. C and B vs. C.
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
Zachary Buchwald
Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA
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
Similar Abstracts
text_snippet
Abstract
2024 ASCO Genitourinary Cancers Symposium
First Author: Natalie Charnley
text_snippet
Abstract
2024 ASCO Annual Meeting
First Author: Ahmad A. Tarhini
text_snippet
Abstract
2022 ASCO Genitourinary Cancers Symposium
First Author: Petros Grivas
text_snippet
Abstract
2023 ASCO Annual Meeting
First Author: Shiaowen David Hsu
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