Adaptive Dosing of Nivolumab + Ipilimumab Immunotherapy Based Upon Early, Interim Radiographic Assessment in Advanced Melanoma (The ADAPT-IT Study)

Authors

Michael A. Postow, Memorial Sloan Kettering Cancer Center, New York, NY.Follow
Debra A. Goldman, Memorial Sloan Kettering Cancer Center, New York, NY.
Alexander N. Shoushtari, Memorial Sloan Kettering Cancer Center, New York, NY.Follow
Allison Betof Warner, Memorial Sloan Kettering Cancer Center, New York, NY.Follow
Margaret K. Callahan, Memorial Sloan Kettering Cancer Center, New York, NY.Follow
Parisa Momtaz, Memorial Sloan Kettering Cancer Center, New York, NY.Follow
James W. Smithy, Memorial Sloan Kettering Cancer Center, New York, NY.
Ellesa Naito, Memorial Sloan Kettering Cancer Center, New York, NY.
Marina K. Cugliari, Memorial Sloan Kettering Cancer Center, New York, NY.
Vladislav Raber, Memorial Sloan Kettering Cancer Center, New York, NY.
Omar Eton, Hartford Healthcare, Hartford, CT.
Suresh G. Nair MD, Lehigh Valley Health NetworkFollow
Katherine S. Panageas, Memorial Sloan Kettering Cancer Center, New York, NY.Follow
Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY.Follow
Paul B. Chapman, Memorial Sloan Kettering Cancer Center, New York, NY.Follow

Document Type

Article

Publication Date

12-20-2021

Publication Title

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

E-ISSN

1527-7755

Department(s)

Hematology-Medical Oncology Division

Abstract

PURPOSE: Nivolumab + ipilimumab (nivo + ipi) is highly efficacious but has high toxicity. Standard treatment in advanced melanoma is four doses of nivo + ipi followed by nivo alone. Whether four doses of nivo + ipi are needed is unclear. METHODS: The Adaptively Dosed ImmunoTherapy Trial (ADAPT-IT) study (NCT03122522) is a multicenter, single-arm phase II clinical trial. Patients received two doses of nivo (1 mg/kg) + ipi (3 mg/kg) followed by a computed tomography scan at week 6. Patients without new lesions or index lesion tumor growth of > 4% had protocol-defined early favorable antitumor effect (FATE) and ceased nivo + ipi, transitioning to nivo monotherapy. Patients without FATE at week 6 received the standard third and fourth doses of nivo + ipi followed by nivo monotherapy. The primary end point was response rate by RECIST 1.1 at week 12. Secondary end points included additional efficacy assessments and safety. RESULTS: Sixty patients were enrolled; 41 patients (68%) had FATE at week 6 and met criteria for stopping nivo + ipi. Best overall response rates by RECIST at week 12 or any time afterward were 48% (95% CI, 35 to 62) and 58% (95% CI, 45 to 71), respectively. With a median follow-up of 25 months, the estimated 18-month progression-free survival and overall survival are 52% and 80%, respectively. Fifty seven percent of patients had grade 3-5 treatment-related toxicity. CONCLUSION: The efficacy and toxicity of standard four dose nivo + ipi induction therapy in melanoma is likely driven by the first two doses. An interim computed tomography scan after two doses guided cessation of combination dosing and identified almost all responders. Longer follow-up and further study are needed to fully understand the implications of a shortened induction course of nivo + ipi.

First Page

JCO2101570

DOI

10.1200/JCO.21.01570

PubMed ID

34928709

Recommended Citation

Postow, M. A., Goldman, D. A., Shoushtari, A. N., Betof Warner, A., Callahan, M. K., Momtaz, P., Smithy, J. W., Naito, E., Cugliari, M. K., Raber, V., Eton, O., Nair, S. G., Panageas, K. S., Wolchok, J. D., & Chapman, P. B. (2021). Adaptive Dosing of Nivolumab + Ipilimumab Immunotherapy Based Upon Early, Interim Radiographic Assessment in Advanced Melanoma (The ADAPT-IT Study). LVHN Scholarly Works. Retrieved from https://scholarlyworks.lvhn.org/research-historical-works/4
DOI: 10.1200/JCO.21.01570