Nemvaleukin alfa, a modified interleukin-2 cytokine, as monotherapy and with pembrolizumab in patients with advanced solid tumors (ARTISTRY-1)
Background Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel, engineered cytokine that selectively binds to the intermediate-affinity interleukin-2 receptor, preferentially activating CD8+ T cells and natural killer cells, with minimal expansion of regulatory T cells, thereby mitigating the risk...
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BMJ Publishing Group
2024-11-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/11/e010143.full |
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| author | Lucy Gilbert Jameel Muzaffar Vamsidhar Velcheti Anna Spreafico Emiliano Calvo David F McDermott Marc S Ernstoff Valentina Boni Karl D Lewis Ira Winer Olivier Dumas Aman Chauhan Arvind Chaudhry Christoper J Hoimes Seth D Rosen Debora S Bruno James F Strauss Rita Dalal Ulka N Vaishampayan Quincy S Chu |
| author_facet | Lucy Gilbert Jameel Muzaffar Vamsidhar Velcheti Anna Spreafico Emiliano Calvo David F McDermott Marc S Ernstoff Valentina Boni Karl D Lewis Ira Winer Olivier Dumas Aman Chauhan Arvind Chaudhry Christoper J Hoimes Seth D Rosen Debora S Bruno James F Strauss Rita Dalal Ulka N Vaishampayan Quincy S Chu |
| author_sort | Lucy Gilbert |
| collection | DOAJ |
| description | Background Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel, engineered cytokine that selectively binds to the intermediate-affinity interleukin-2 receptor, preferentially activating CD8+ T cells and natural killer cells, with minimal expansion of regulatory T cells, thereby mitigating the risk of toxicities associated with high-affinity interleukin-2 receptor activation. Clinical outcomes with nemvaleukin are unknown. ARTISTRY-1 investigated the safety, recommended phase 2 dose (RP2D), and antitumor activity of nemvaleukin in patients with advanced solid tumors.Methods This was a three-part, open-label, phase 1/2 study: part A, dose-escalation monotherapy, part B, dose-expansion monotherapy, and part C, combination therapy with pembrolizumab. The study was conducted at 32 sites in 7 countries. Adult patients with advanced solid tumors were enrolled and received intravenous nemvaleukin once daily on days 1–5 (21-day cycle) at 0.1–10 µg/kg/day (part A), or at the RP2D (part B), or with pembrolizumab (part C). Primary endpoints were RP2D selection and dose-limiting toxicities (part A), and overall response rate (ORR) and safety (parts B and C).Results From July 2016 to March 2023, 243 patients were enrolled and treated (46, 74, and 166 in parts A, B, and C, respectively). The maximum tolerated dose was not reached. RP2D was determined as 6 µg/kg/day. ORR with nemvaleukin monotherapy was 10% (7/68; 95% CI 4 to 20), with seven partial responses (melanoma, n=4; renal cell carcinoma, n=3). Robust CD8+ T and natural killer cell expansion, and minimal regulatory T cell expansion were observed following nemvaleukin treatment. ORR with nemvaleukin plus pembrolizumab was 13% (19/144; 95% CI 8 to 20), with 5 complete and 14 partial responses; 6 responses were in PD-(L)1 inhibitor-approved and five in PD-(L)1 inhibitor-unapproved tumor types. Three responses were in patients with platinum-resistant ovarian cancer. The most common grade 3–4 treatment-related adverse events (TRAEs) in parts B and C, respectively, were neutropenia (49%, 21%) and anemia (10%, 11%); 4% of patients in each part discontinued due to TRAEs.Conclusions Nemvaleukin was well tolerated and demonstrated promising antitumor activity across heavily pretreated advanced solid tumors. Phase 2/3 studies of nemvaleukin are ongoing.Trial registration number NCT02799095. |
| format | Article |
| id | doaj-art-effa100105de4e66b831c7e9c39c98ff |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-effa100105de4e66b831c7e9c39c98ff2024-11-27T04:55:13ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-11-01121110.1136/jitc-2024-010143Nemvaleukin alfa, a modified interleukin-2 cytokine, as monotherapy and with pembrolizumab in patients with advanced solid tumors (ARTISTRY-1)Lucy Gilbert0Jameel Muzaffar1Vamsidhar Velcheti2Anna Spreafico3Emiliano Calvo4David F McDermott5Marc S Ernstoff6Valentina Boni7Karl D Lewis8Ira Winer9Olivier Dumas10Aman Chauhan11Arvind Chaudhry12Christoper J Hoimes13Seth D Rosen14Debora S Bruno15James F Strauss16Rita Dalal17Ulka N Vaishampayan18Quincy S Chu19Division of Gynecologic Oncology, The Gerald Bronfman Department of Oncology, McGill University Health Centre, Montreal, Quebec, CanadaDepartment of Medicine, Duke University School of Medicine, Durham, North Carolina, USALaura and Isaac Perlmutter Cancer Center, New York University, New York, New York, USADepartment of Medicine, Division of Medical Oncology and Hematology, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, CanadaSTART Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Madrid, SpainBeth Israel Deaconess Medical Center, Boston, Massachusetts, USADivision of Cancer Treatment & Diagnosis, National Cancer Institute, NIH, Bethesda, Maryland, USASTART Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Madrid, SpainUniversity of Colorado School of Medicine, Aurora, Colorado, USABarbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USACHU de Québec-Université Laval, Quebec City, Quebec, CanadaSylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, USASummit Cancer Centers, Spokane, Washington, USAPhase I Program, Case Comprehensive Cancer Center, University Hospitals, Cleveland, Ohio, USAHematology Oncology Association of the Treasure Coast, Port St. Lucie, Florida, USADepartment of Medicine, University Hospitals Cleveland Medical Center, Seidman Cancer Center, Cleveland, Ohio, USAMary Crowley Cancer Research Center, Dallas, Texas, USAMural Oncology, Inc, Waltham, Massachusetts, USADivison of Hematology/Oncology, University of Michigan, Ann Arbor, Michigan, USAUniversity of Alberta/Alberta Health Services, Cross Cancer Institute, Edmonton, Alberta, CanadaBackground Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel, engineered cytokine that selectively binds to the intermediate-affinity interleukin-2 receptor, preferentially activating CD8+ T cells and natural killer cells, with minimal expansion of regulatory T cells, thereby mitigating the risk of toxicities associated with high-affinity interleukin-2 receptor activation. Clinical outcomes with nemvaleukin are unknown. ARTISTRY-1 investigated the safety, recommended phase 2 dose (RP2D), and antitumor activity of nemvaleukin in patients with advanced solid tumors.Methods This was a three-part, open-label, phase 1/2 study: part A, dose-escalation monotherapy, part B, dose-expansion monotherapy, and part C, combination therapy with pembrolizumab. The study was conducted at 32 sites in 7 countries. Adult patients with advanced solid tumors were enrolled and received intravenous nemvaleukin once daily on days 1–5 (21-day cycle) at 0.1–10 µg/kg/day (part A), or at the RP2D (part B), or with pembrolizumab (part C). Primary endpoints were RP2D selection and dose-limiting toxicities (part A), and overall response rate (ORR) and safety (parts B and C).Results From July 2016 to March 2023, 243 patients were enrolled and treated (46, 74, and 166 in parts A, B, and C, respectively). The maximum tolerated dose was not reached. RP2D was determined as 6 µg/kg/day. ORR with nemvaleukin monotherapy was 10% (7/68; 95% CI 4 to 20), with seven partial responses (melanoma, n=4; renal cell carcinoma, n=3). Robust CD8+ T and natural killer cell expansion, and minimal regulatory T cell expansion were observed following nemvaleukin treatment. ORR with nemvaleukin plus pembrolizumab was 13% (19/144; 95% CI 8 to 20), with 5 complete and 14 partial responses; 6 responses were in PD-(L)1 inhibitor-approved and five in PD-(L)1 inhibitor-unapproved tumor types. Three responses were in patients with platinum-resistant ovarian cancer. The most common grade 3–4 treatment-related adverse events (TRAEs) in parts B and C, respectively, were neutropenia (49%, 21%) and anemia (10%, 11%); 4% of patients in each part discontinued due to TRAEs.Conclusions Nemvaleukin was well tolerated and demonstrated promising antitumor activity across heavily pretreated advanced solid tumors. Phase 2/3 studies of nemvaleukin are ongoing.Trial registration number NCT02799095.https://jitc.bmj.com/content/12/11/e010143.full |
| spellingShingle | Lucy Gilbert Jameel Muzaffar Vamsidhar Velcheti Anna Spreafico Emiliano Calvo David F McDermott Marc S Ernstoff Valentina Boni Karl D Lewis Ira Winer Olivier Dumas Aman Chauhan Arvind Chaudhry Christoper J Hoimes Seth D Rosen Debora S Bruno James F Strauss Rita Dalal Ulka N Vaishampayan Quincy S Chu Nemvaleukin alfa, a modified interleukin-2 cytokine, as monotherapy and with pembrolizumab in patients with advanced solid tumors (ARTISTRY-1) Journal for ImmunoTherapy of Cancer |
| title | Nemvaleukin alfa, a modified interleukin-2 cytokine, as monotherapy and with pembrolizumab in patients with advanced solid tumors (ARTISTRY-1) |
| title_full | Nemvaleukin alfa, a modified interleukin-2 cytokine, as monotherapy and with pembrolizumab in patients with advanced solid tumors (ARTISTRY-1) |
| title_fullStr | Nemvaleukin alfa, a modified interleukin-2 cytokine, as monotherapy and with pembrolizumab in patients with advanced solid tumors (ARTISTRY-1) |
| title_full_unstemmed | Nemvaleukin alfa, a modified interleukin-2 cytokine, as monotherapy and with pembrolizumab in patients with advanced solid tumors (ARTISTRY-1) |
| title_short | Nemvaleukin alfa, a modified interleukin-2 cytokine, as monotherapy and with pembrolizumab in patients with advanced solid tumors (ARTISTRY-1) |
| title_sort | nemvaleukin alfa a modified interleukin 2 cytokine as monotherapy and with pembrolizumab in patients with advanced solid tumors artistry 1 |
| url | https://jitc.bmj.com/content/12/11/e010143.full |
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