Phase II basket trial of Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) SWOG S1609: pancreatic neuroendocrine neoplasm (PNEN) cohort
Purpose SWOG S1609 Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) studied the efficacy of ipilimumab combined with nivolumab across multiple rare tumor types. We report the results of the pancreatic neuroendocrine neoplasm (PNEN) cohort.Experimental design Treatment consisted of ipili...
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BMJ Publishing Group
2025-06-01
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| Series: | Journal for ImmunoTherapy of Cancer |
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| author | Ignacio I Wistuba Jianhua Zhang Anup Kasi Hong Chen Seunghee Kim-Schulze Holden T Maecker Elad Sharon Razelle Kurzrock Sacha Gnjatic Young Kwang Chae Jiexin Zhang Jianjun Zhang Sandip Pravin Patel Cara L Haymaker Megan Othus Charles Blanke Edwin Parra Gheath Al-Atrash Caroline Duault J Jack Lee Helen X Chen Edgar Gonzalez-Kozlova Dzifa Yawa Duose Luisa Solis Soto Ganiraju Manyam Christopher W Ryan Jillian Fisher Bhavana Konda Mark Walshauser Caddie Laberiano Fernandez Raja Luthra Christine M Magner |
| author_facet | Ignacio I Wistuba Jianhua Zhang Anup Kasi Hong Chen Seunghee Kim-Schulze Holden T Maecker Elad Sharon Razelle Kurzrock Sacha Gnjatic Young Kwang Chae Jiexin Zhang Jianjun Zhang Sandip Pravin Patel Cara L Haymaker Megan Othus Charles Blanke Edwin Parra Gheath Al-Atrash Caroline Duault J Jack Lee Helen X Chen Edgar Gonzalez-Kozlova Dzifa Yawa Duose Luisa Solis Soto Ganiraju Manyam Christopher W Ryan Jillian Fisher Bhavana Konda Mark Walshauser Caddie Laberiano Fernandez Raja Luthra Christine M Magner |
| author_sort | Ignacio I Wistuba |
| collection | DOAJ |
| description | Purpose SWOG S1609 Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) studied the efficacy of ipilimumab combined with nivolumab across multiple rare tumor types. We report the results of the pancreatic neuroendocrine neoplasm (PNEN) cohort.Experimental design Treatment consisted of ipilimumab 1 mg/kg intravenously every 6 weeks with nivolumab 240 mg intravenously every 2 weeks. The primary endpoint was overall response rate (ORR) (Response Evaluation Criteria In Solid TumorsRECIST V.1.1). Secondary endpoints include progression-free survival (PFS), overall survival (OS), and toxicity. Clinical benefit rate (includes ORR plus stable disease (SD)>6 months was examined. Correlative studies were performed. The trial was conducted by the National Cancer Institute/Southwest Oncology Group Early Therapeutics and Rare Cancers Committee and opened at >1,000 sites.Results 19 patients with PNEN were enrolled. The median number of lines of prior therapy was 2 (range: 0–4). The ORR was 11% (2/19 patients); the clinical benefit rate (CBR; stable disease >6 months+partial response+complete response), 26% (5/19). The median PFS was 3 months; median OS, 24 months. The longest PFSs were 26 (intermediate grade PNEN), 31 (low grade) and 39+months (intermediate grade). The most common toxicities were fatigue (47% of patients) and aspartate aminotransferase (AST) elevation (32%); the most common grade 3/4 immune-related adverse event (AE) was AST (32%) and bilirubin elevation (26%), with no grade 5 events. Programmed death-ligand 1 expression by chromogenic immunohistochemistry (N=12 patients assessed) did not associate with ORR; tumor mutation burden (TMB) was high in three patients; one of the two patients with partial remission (PFS=26 months) had high TMB (150 mutations/mb). Peripheral effector memory T-cell activation (N=11 patients assessed by cytometry by time-of-flight with 5 having longitudinal analysis) was associated with response, though the number of patients evaluated was limited.Conclusions Low-dose ipilimumab plus nivolumab demonstrated an 11% ORR and 26% CBR (includes SD>6 months) in patients with refractory PNEN, with durable benefit (>2 years) in 3 (16%) patients.Trial registration number NCT02834013. |
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| issn | 2051-1426 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-65f07993b70a4bd8a5202f36fb8b5b0f2025-07-01T02:50:15ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-06-0113610.1136/jitc-2025-011760Phase II basket trial of Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) SWOG S1609: pancreatic neuroendocrine neoplasm (PNEN) cohortIgnacio I Wistuba0Jianhua Zhang1Anup Kasi2Hong Chen3Seunghee Kim-Schulze4Holden T Maecker5Elad Sharon6Razelle Kurzrock7Sacha Gnjatic8Young Kwang Chae9Jiexin Zhang10Jianjun Zhang11Sandip Pravin Patel12Cara L Haymaker13Megan Othus14Charles Blanke15Edwin Parra16Gheath Al-Atrash17Caroline Duault18J Jack Lee19Helen X Chen20Edgar Gonzalez-Kozlova21Dzifa Yawa Duose22Luisa Solis Soto23Ganiraju Manyam24Christopher W Ryan25Jillian Fisher26Bhavana Konda27Mark Walshauser28Caddie Laberiano Fernandez29Raja Luthra30Christine M Magner3111 University of Texas MD Anderson Cancer Center, Houston, Texas, USA12 Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA5 KUMC, Kansas City, Kansas, USA11 University of Texas MD Anderson Cancer Center, Houston, Texas, USA13 Icahn School of Medicine at Mount Sinai, New York, New York, USA14 Stanford University School of Medicine, Stanford, California, USA19 National Cancer Institute, Bethesda, Maryland, USA22 Medical College of Wisconsin, Milwaukee, Wisconsin, USA15 Medicine - Hem/Onc, Icahn School of Medicine at Mount Sinai, New York, New York, USA3 Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA8 Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Hosuton, Texas, USA16 Thoracic Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, UK1 UC San Diego Health Moores Cancer Center, La Jolla, California, USA4 Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA20 Fred Hutchinson Cancer Research Center, Seattle, Washington, USA21 OHSU, Portland, Oregon, USA4 Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA11 University of Texas MD Anderson Cancer Center, Houston, Texas, USA9 Institute for Immunity, Transplantation, Infections, Stanford University School of Medicine, Stanford, California, USA8 Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Hosuton, Texas, USA18 CTEP, National Cancer Institute, Bethesda, Maryland, USA10 Precision Immunology Institute and Tisch Cancer Institute, Department of Immunology, Icahn School of Medicine at Mount Sinai, New York, New York, USA11 University of Texas MD Anderson Cancer Center, Houston, Texas, USA4 Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA11 University of Texas MD Anderson Cancer Center, Houston, Texas, USA21 OHSU, Portland, Oregon, USA2 University of Washington, Seattle, Washington, USA6 Internal Medicine, Division Of Medical Oncology, The Ohio State University, Columbus, Ohio, USA7 Cancer Care Center of O’Fallon, O’Fallon, Illinois, USA11 University of Texas MD Anderson Cancer Center, Houston, Texas, USA11 University of Texas MD Anderson Cancer Center, Houston, Texas, USA17 SWOG, San Antonio, Texas, USAPurpose SWOG S1609 Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) studied the efficacy of ipilimumab combined with nivolumab across multiple rare tumor types. We report the results of the pancreatic neuroendocrine neoplasm (PNEN) cohort.Experimental design Treatment consisted of ipilimumab 1 mg/kg intravenously every 6 weeks with nivolumab 240 mg intravenously every 2 weeks. The primary endpoint was overall response rate (ORR) (Response Evaluation Criteria In Solid TumorsRECIST V.1.1). Secondary endpoints include progression-free survival (PFS), overall survival (OS), and toxicity. Clinical benefit rate (includes ORR plus stable disease (SD)>6 months was examined. Correlative studies were performed. The trial was conducted by the National Cancer Institute/Southwest Oncology Group Early Therapeutics and Rare Cancers Committee and opened at >1,000 sites.Results 19 patients with PNEN were enrolled. The median number of lines of prior therapy was 2 (range: 0–4). The ORR was 11% (2/19 patients); the clinical benefit rate (CBR; stable disease >6 months+partial response+complete response), 26% (5/19). The median PFS was 3 months; median OS, 24 months. The longest PFSs were 26 (intermediate grade PNEN), 31 (low grade) and 39+months (intermediate grade). The most common toxicities were fatigue (47% of patients) and aspartate aminotransferase (AST) elevation (32%); the most common grade 3/4 immune-related adverse event (AE) was AST (32%) and bilirubin elevation (26%), with no grade 5 events. Programmed death-ligand 1 expression by chromogenic immunohistochemistry (N=12 patients assessed) did not associate with ORR; tumor mutation burden (TMB) was high in three patients; one of the two patients with partial remission (PFS=26 months) had high TMB (150 mutations/mb). Peripheral effector memory T-cell activation (N=11 patients assessed by cytometry by time-of-flight with 5 having longitudinal analysis) was associated with response, though the number of patients evaluated was limited.Conclusions Low-dose ipilimumab plus nivolumab demonstrated an 11% ORR and 26% CBR (includes SD>6 months) in patients with refractory PNEN, with durable benefit (>2 years) in 3 (16%) patients.Trial registration number NCT02834013.https://jitc.bmj.com/content/13/6/e011760.full |
| spellingShingle | Ignacio I Wistuba Jianhua Zhang Anup Kasi Hong Chen Seunghee Kim-Schulze Holden T Maecker Elad Sharon Razelle Kurzrock Sacha Gnjatic Young Kwang Chae Jiexin Zhang Jianjun Zhang Sandip Pravin Patel Cara L Haymaker Megan Othus Charles Blanke Edwin Parra Gheath Al-Atrash Caroline Duault J Jack Lee Helen X Chen Edgar Gonzalez-Kozlova Dzifa Yawa Duose Luisa Solis Soto Ganiraju Manyam Christopher W Ryan Jillian Fisher Bhavana Konda Mark Walshauser Caddie Laberiano Fernandez Raja Luthra Christine M Magner Phase II basket trial of Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) SWOG S1609: pancreatic neuroendocrine neoplasm (PNEN) cohort Journal for ImmunoTherapy of Cancer |
| title | Phase II basket trial of Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) SWOG S1609: pancreatic neuroendocrine neoplasm (PNEN) cohort |
| title_full | Phase II basket trial of Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) SWOG S1609: pancreatic neuroendocrine neoplasm (PNEN) cohort |
| title_fullStr | Phase II basket trial of Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) SWOG S1609: pancreatic neuroendocrine neoplasm (PNEN) cohort |
| title_full_unstemmed | Phase II basket trial of Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) SWOG S1609: pancreatic neuroendocrine neoplasm (PNEN) cohort |
| title_short | Phase II basket trial of Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) SWOG S1609: pancreatic neuroendocrine neoplasm (PNEN) cohort |
| title_sort | phase ii basket trial of dual anti ctla 4 and anti pd 1 blockade in rare tumors dart swog s1609 pancreatic neuroendocrine neoplasm pnen cohort |
| url | https://jitc.bmj.com/content/13/6/e011760.full |
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