Early On-Treatment Assessment of T Cells, Cytokines, and Tumor DNA with Adaptively Dosed Nivolumab + Ipilimumab: Final Results from the Phase 2 ADAPT-IT Study

The Adaptively Dosed ImmunoTherapy Trial (ADAPT-IT;NCT03122522) investigated adaptive ipilimumab discontinuation in melanoma based on early radiographic assessment. Initial findings indicated similar effectiveness compared with conventional nivolumab-ipilimumab (nivo-ipi). Exploratory biomarker anal...

Full description

Saved in:

Bibliographic Details
Published in:	Clinical cancer research Vol. 30; no. 16; pp. 3407 - 3415
Main Authors:	Smithy, James W, Kalvin, Hannah L, Ehrich, Fiona D, Shah, Ronak, Adamow, Matthew, Raber, Vladislav, Maher, Collen A, Kleman, Jenna, McIntyre, Deborah A G, Shoushtari, Alexander N, Betof Warner, Allison, Callahan, Margaret K, Momtaz, Parisa, Eton, Omar, Nair, Suresh, Wolchok, Jedd D, Chapman, Paul B, Berger, Michael F, Panageas, Katherine S, Postow, Michael A
Format:	Journal Article
Language:	English
Published:	United States 15-08-2024
Subjects:	Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biomarkers, Tumor Circulating Tumor DNA Cytokines - metabolism DNA, Neoplasm Female Humans Ipilimumab - administration & dosage Male Melanoma - drug therapy Melanoma - mortality Melanoma - pathology Middle Aged Nivolumab - administration & dosage T-Lymphocytes - immunology T-Lymphocytes - metabolism
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The Adaptively Dosed ImmunoTherapy Trial (ADAPT-IT;NCT03122522) investigated adaptive ipilimumab discontinuation in melanoma based on early radiographic assessment. Initial findings indicated similar effectiveness compared with conventional nivolumab-ipilimumab (nivo-ipi). Exploratory biomarker analyses and final clinical results are now reported. Patients with unresectable melanoma received two doses of nivo-ipi. Radiographic assessment at Week 6 informed continuation of ipilimumab before nivolumab maintenance. The primary endpoint was overall response rate at Week 12. Plasma was assayed for circulating tumor DNA and 10 cytokines using a multiplex immunoassay. Flow cytometry of peripheral blood mononuclear cells was performed with an 11-color panel. Among the treated patients, expansion of proliferating T-cell populations was observed in responders and nonresponders. Baseline IL6 levels were low in patients achieving an objective radiographic response (median 1.30 vs. 2.86 pg/mL; P = 0.025). High baseline IL6 levels were associated with short progression-free survival [PFS; HR = 1.24, 95% confidence interval (CI), 1.01-1.52; P = 0.041]. At Week 6, patients with response had lower average tumor variant allele fractions than nonresponders (median 0.000 vs. 0.019; P = 0.014). Greater increases in average variant allele fractions from baseline to Week 6 correlated with short PFS (HR = 1.11, 95% CI, 1.01-1.21; P = 0.023). Week 12 overall response rate was 47% (95% CI, 35%-59%) with a median follow-up of 34 months among survivors. Median PFS was 21 months (95% CI, 10-not reached); 76% of responses (95% CI, 64%-91%) persisted at 36 months. Adaptively dosed nivo-ipi responses are durable and resemble historical data for conventional nivo-ipi. Baseline IL6 and circulating tumor DNA changes during treatment warrant further study as biomarkers of nivo-ipi response.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1078-0432 1557-3265 1557-3265
DOI:	10.1158/1078-0432.CCR-23-3643