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.
Publication/Presentation Date
5-20-2024
Abstract
PURPOSE: ADAPT-IT (NCT03122522) investigated adaptive ipilimumab discontinuation in melanoma based on early radiographic assessment. Initial findings indicated similar effectiveness compared to conventional nivolumab-ipilimumab (nivo-ipi). Exploratory biomarker analyses and final clinical results are now reported.
PATIENTS AND METHODS: 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 (ORR) at Week 12. Plasma was assayed for circulating tumor DNA (ctDNA) and ten cytokines using a multiplex immunoassay. Flow cytometry of peripheral blood mononuclear cells was performed with an 11-color panel.
RESULTS: Among treated patients, expansion of proliferating T-cell populations was observed in both responders and non-responders. Baseline IL-6 levels were lower in patients achieving an objective radiographic response (median 1.30 vs 2.86 pg/mL; p=0.025). Higher baseline IL-6 levels were associated with shorter progression-freesurvival (PFS; hazard ratio (HR)=1.24, 95% CI:1.01-1.52; p=0.041). At Week 6, patients with response had lower average tumor variant allele fractions (VAF) compared to non-responders (median 0.000 v 0.019; p=0.014). Greater increases in average VAF from baseline to Week 6 correlated with shorter PFS (HR=1.11, 95% CI:1.01-1.21; p=0.023). Week 12 ORR 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.
CONCLUSIONS: Adaptively dosed nivo-ipi responses are durable and resemble historical data for conventional nivo-ipi. Baseline IL-6 and ctDNA changes during treatment warrant further study as biomarkers of nivo-ipi response.
First Page
100401
Last Page
100401
ISSN
1557-3265
Published In/Presented At
Smithy, J. W., Kalvin, H. L., Ehrich, F. D., Shah, R., Adamow, M., Raber, V., Maher, C. A., Kleman, J., McIntyre, D. A. G., Shoushtari, A. N., Betof Warner, A., Callahan, M. K., Momtaz, P., Eton, O., Nair, S., Wolchok, J. D., Chapman, P. B., Berger, M. F., Panageas, K. S., & Postow, M. A. (2024). 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. Clinical cancer research : an official journal of the American Association for Cancer Research, 10.1158/1078-0432.CCR-23-3643. Advance online publication. https://doi.org/10.1158/1078-0432.CCR-23-3643
Disciplines
Medicine and Health Sciences
PubMedID
38767650
Department(s)
Department of Medicine, Hematology-Medical Oncology Division
Document Type
Article