Phase I study of efineptakin alfa (NT-I7) for the treatment of Kaposi sarcoma
Background CD4+ T-cell lymphocytopenia and immune dysfunction are factors that drive the onset and persistence of Kaposi sarcoma (KS) in people with (PWH) and without HIV. Standard chemotherapy agents for KS can contribute to increasing CD4+ T cell lymphocytopenia. IL-7 is a cytokine that is essenti...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2025-02-01
|
| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/2/e010291.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1825206942551769088 |
|---|---|
| author | Leonard D’Amico Martin Cheever Steven P Fling Anna Wright Kathryn Lurain Ramya Ramaswami Irene Ekwede Thomas S Uldrick Robert Yarchoan Judith C Kaiser Angela Shaulov Kask Manoj P Menon Paul Couey Eli Burnham Allysson Angeldekao Byung Ha Lee Li-Lian Kwok Chia-Ching Jackie Wang |
| author_facet | Leonard D’Amico Martin Cheever Steven P Fling Anna Wright Kathryn Lurain Ramya Ramaswami Irene Ekwede Thomas S Uldrick Robert Yarchoan Judith C Kaiser Angela Shaulov Kask Manoj P Menon Paul Couey Eli Burnham Allysson Angeldekao Byung Ha Lee Li-Lian Kwok Chia-Ching Jackie Wang |
| author_sort | Leonard D’Amico |
| collection | DOAJ |
| description | Background CD4+ T-cell lymphocytopenia and immune dysfunction are factors that drive the onset and persistence of Kaposi sarcoma (KS) in people with (PWH) and without HIV. Standard chemotherapy agents for KS can contribute to increasing CD4+ T cell lymphocytopenia. IL-7 is a cytokine that is essential in T-cell development, proliferation and homeostasis. In PWH, IL-7 administration leads to increased numbers of circulating central memory and naïve T-cell phenotypes.Methods In this multicenter phase I study with a 3+3 dose escalation design, participants with KS with or without HIV received up to four intramuscular injections of IL-7 (NT-I7) every 9 weeks. The primary endpoint of the study was to evaluate safety over three escalating dose levels (DL) of NT-I7 (DL1:480 µg/kg, DL2: 960 µg/kg and DL3: 1200 µg/kg) and identify a maximum tolerated dose. Secondary endpoints included evaluation of antitumor activity per the modified AIDS Clinical Trials Group Criteria and assessment of the effect of NT-I7 on the kinetics of CD4+ and CD8+ T-cells.Results Eight cisgender male participants (five with HIV infection) were enrolled. Six participants were treated at DL1, and two were treated at DL2. The study was closed to accrual after enrolment of the second participant on DL2 due to termination of study funding. Four of the eight participants (three in DL1 and one in DL2) completed all four doses of the NT-I7. With regard to treatment-emergent adverse events (AEs), all participants had <grade 2 AEs, which included injection site reaction and alanine aminotransferase increase. Injection site reaction was a dose-limiting toxicity in one participant at DL1. The overall KS objective response rate to NT-I7 was 42.9% (95% CI 9.9%, 81.6%) and all three responders were PWH. Absolute lymphocyte counts, CD4+ and CD8+ T-cell counts increased among all participants following administration of NT-I7. Participants who experienced a response had HIV and lower CD4/CD8 ratio at baseline and throughout the study as compared with those who did not have KS response to NT-I7.Conclusions Preliminary data demonstrate safety and activity of IL-7 in patients with KS and activity specifically among individuals HIV-associated KS.Trial registration number NCT04893018. |
| format | Article |
| id | doaj-art-52ce46a83e874aafbd8a1f0971c6d971 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-52ce46a83e874aafbd8a1f0971c6d9712025-02-07T04:45:10ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-02-0113210.1136/jitc-2024-010291Phase I study of efineptakin alfa (NT-I7) for the treatment of Kaposi sarcomaLeonard D’Amico0Martin Cheever1Steven P Fling2Anna Wright3Kathryn Lurain4Ramya Ramaswami5Irene Ekwede6Thomas S Uldrick7Robert Yarchoan8Judith C Kaiser9Angela Shaulov Kask10Manoj P Menon11Paul Couey12Eli Burnham13Allysson Angeldekao14Byung Ha Lee15Li-Lian Kwok16Chia-Ching Jackie Wang17Cancer Immunotherapy Trials Network (CITN), Fred Hutchinson Cancer Center, Seattle, Washington, USACancer Immunotherapy Trials Network (CITN), Fred Hutchinson Cancer Center, Seattle, Washington, USACancer Immunotherapy Trials Network (CITN), Fred Hutchinson Cancer Center, Seattle, Washington, USACancer Immunotherapy Trials Network (CITN), Fred Hutchinson Cancer Center, Seattle, Washington, USAHIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland, USAHIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland, USAHIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland, USACancer Immunotherapy Trials Network (CITN), Fred Hutchinson Cancer Center, Seattle, Washington, USAHIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, Maryland, USACancer Immunotherapy Trials Network (CITN), Fred Hutchinson Cancer Center, Seattle, Washington, USACancer Immunotherapy Trials Network (CITN), Fred Hutchinson Cancer Center, Seattle, Washington, USAFred Hutchinson Cancer Research Center, Seattle, Washington, USADivision of Hematology and Medical Oncology, University of California San Francisco (UCSF) Helen Diller Comprehensive Cancer Center, San Francisco, California, USAHarborview Medical Center, Seattle, Washington, USAHarborview Medical Center, Seattle, Washington, USANeoImmuneTech Inc, Rockville, Maryland, USACytel (Shanghai) Co Ltd, Shanghai, ChinaDivision of Hematology and Medical Oncology, University of California San Francisco (UCSF) Helen Diller Comprehensive Cancer Center, San Francisco, California, USABackground CD4+ T-cell lymphocytopenia and immune dysfunction are factors that drive the onset and persistence of Kaposi sarcoma (KS) in people with (PWH) and without HIV. Standard chemotherapy agents for KS can contribute to increasing CD4+ T cell lymphocytopenia. IL-7 is a cytokine that is essential in T-cell development, proliferation and homeostasis. In PWH, IL-7 administration leads to increased numbers of circulating central memory and naïve T-cell phenotypes.Methods In this multicenter phase I study with a 3+3 dose escalation design, participants with KS with or without HIV received up to four intramuscular injections of IL-7 (NT-I7) every 9 weeks. The primary endpoint of the study was to evaluate safety over three escalating dose levels (DL) of NT-I7 (DL1:480 µg/kg, DL2: 960 µg/kg and DL3: 1200 µg/kg) and identify a maximum tolerated dose. Secondary endpoints included evaluation of antitumor activity per the modified AIDS Clinical Trials Group Criteria and assessment of the effect of NT-I7 on the kinetics of CD4+ and CD8+ T-cells.Results Eight cisgender male participants (five with HIV infection) were enrolled. Six participants were treated at DL1, and two were treated at DL2. The study was closed to accrual after enrolment of the second participant on DL2 due to termination of study funding. Four of the eight participants (three in DL1 and one in DL2) completed all four doses of the NT-I7. With regard to treatment-emergent adverse events (AEs), all participants had <grade 2 AEs, which included injection site reaction and alanine aminotransferase increase. Injection site reaction was a dose-limiting toxicity in one participant at DL1. The overall KS objective response rate to NT-I7 was 42.9% (95% CI 9.9%, 81.6%) and all three responders were PWH. Absolute lymphocyte counts, CD4+ and CD8+ T-cell counts increased among all participants following administration of NT-I7. Participants who experienced a response had HIV and lower CD4/CD8 ratio at baseline and throughout the study as compared with those who did not have KS response to NT-I7.Conclusions Preliminary data demonstrate safety and activity of IL-7 in patients with KS and activity specifically among individuals HIV-associated KS.Trial registration number NCT04893018.https://jitc.bmj.com/content/13/2/e010291.full |
| spellingShingle | Leonard D’Amico Martin Cheever Steven P Fling Anna Wright Kathryn Lurain Ramya Ramaswami Irene Ekwede Thomas S Uldrick Robert Yarchoan Judith C Kaiser Angela Shaulov Kask Manoj P Menon Paul Couey Eli Burnham Allysson Angeldekao Byung Ha Lee Li-Lian Kwok Chia-Ching Jackie Wang Phase I study of efineptakin alfa (NT-I7) for the treatment of Kaposi sarcoma Journal for ImmunoTherapy of Cancer |
| title | Phase I study of efineptakin alfa (NT-I7) for the treatment of Kaposi sarcoma |
| title_full | Phase I study of efineptakin alfa (NT-I7) for the treatment of Kaposi sarcoma |
| title_fullStr | Phase I study of efineptakin alfa (NT-I7) for the treatment of Kaposi sarcoma |
| title_full_unstemmed | Phase I study of efineptakin alfa (NT-I7) for the treatment of Kaposi sarcoma |
| title_short | Phase I study of efineptakin alfa (NT-I7) for the treatment of Kaposi sarcoma |
| title_sort | phase i study of efineptakin alfa nt i7 for the treatment of kaposi sarcoma |
| url | https://jitc.bmj.com/content/13/2/e010291.full |
| work_keys_str_mv | AT leonarddamico phaseistudyofefineptakinalfanti7forthetreatmentofkaposisarcoma AT martincheever phaseistudyofefineptakinalfanti7forthetreatmentofkaposisarcoma AT stevenpfling phaseistudyofefineptakinalfanti7forthetreatmentofkaposisarcoma AT annawright phaseistudyofefineptakinalfanti7forthetreatmentofkaposisarcoma AT kathrynlurain phaseistudyofefineptakinalfanti7forthetreatmentofkaposisarcoma AT ramyaramaswami phaseistudyofefineptakinalfanti7forthetreatmentofkaposisarcoma AT ireneekwede phaseistudyofefineptakinalfanti7forthetreatmentofkaposisarcoma AT thomassuldrick phaseistudyofefineptakinalfanti7forthetreatmentofkaposisarcoma AT robertyarchoan phaseistudyofefineptakinalfanti7forthetreatmentofkaposisarcoma AT judithckaiser phaseistudyofefineptakinalfanti7forthetreatmentofkaposisarcoma AT angelashaulovkask phaseistudyofefineptakinalfanti7forthetreatmentofkaposisarcoma AT manojpmenon phaseistudyofefineptakinalfanti7forthetreatmentofkaposisarcoma AT paulcouey phaseistudyofefineptakinalfanti7forthetreatmentofkaposisarcoma AT eliburnham phaseistudyofefineptakinalfanti7forthetreatmentofkaposisarcoma AT allyssonangeldekao phaseistudyofefineptakinalfanti7forthetreatmentofkaposisarcoma AT byunghalee phaseistudyofefineptakinalfanti7forthetreatmentofkaposisarcoma AT liliankwok phaseistudyofefineptakinalfanti7forthetreatmentofkaposisarcoma AT chiachingjackiewang phaseistudyofefineptakinalfanti7forthetreatmentofkaposisarcoma |