Spartalizumab in combination with platinum-doublet chemotherapy with or without canakinumab in patients with PD-L1-unselected, metastatic NSCLC
Abstract Background Despite promising outcomes of treatment with anti-programmed cell death (PD)-1/PD-ligand (L)1 agents in combination with platinum-doublet chemotherapy (PDC) in the first-line setting, a significant unmet medical need remains in patients with PD-L1-unselected non-small cell lung c...
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BMC
2024-10-01
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| Online Access: | https://doi.org/10.1186/s12885-024-12841-2 |
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| author | Armando Santoro Garrido Pilar Daniel S.W. Tan Jon Zugazagoitia Frances A. Shepherd Alessandra Bearz Fabrice Barlesi Tae Min Kim Tobias R. Overbeck Enriqueta Felip Can Cai Simantini Eddy Tracey McCulloch Eric S. Schaefer |
| author_facet | Armando Santoro Garrido Pilar Daniel S.W. Tan Jon Zugazagoitia Frances A. Shepherd Alessandra Bearz Fabrice Barlesi Tae Min Kim Tobias R. Overbeck Enriqueta Felip Can Cai Simantini Eddy Tracey McCulloch Eric S. Schaefer |
| author_sort | Armando Santoro |
| collection | DOAJ |
| description | Abstract Background Despite promising outcomes of treatment with anti-programmed cell death (PD)-1/PD-ligand (L)1 agents in combination with platinum-doublet chemotherapy (PDC) in the first-line setting, a significant unmet medical need remains in patients with PD-L1-unselected non-small cell lung cancer (NSCLC). Methods This multicenter, open-label, phase 1b study comprising dose-confirmation and dose-expansion parts investigated the combination of spartalizumab and various PDC regimens, with or without canakinumab, in treatment-naïve patients with PD-L1-unselected, metastatic NSCLC. The primary objectives were to determine maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of spartalizumab, with or without canakinumab, in combination with PDC in the dose-confirmation part and antitumor activity of spartalizumab in the dose-expansion part. Results The MTD/RDE of spartalizumab was 300 mg every 3 weeks (Q3W) when administered with either gemcitabine (1250 mg/m2)/cisplatin (75 mg/m2) (group A; no dose-limiting toxicities [DLTs]), pemetrexed (500 mg/m2)/cisplatin (group B; 2 DLTs: grade 2 posterior reversible encephalopathy syndrome and grade 4 hyponatremia), or paclitaxel (200 mg/m2)/carboplatin area under the curve 6 min*mg/mL (group C; 1 DLT: grade 4 neutropenic colitis). The RDE of canakinumab combined with spartalizumab and pemetrexed/cisplatin (group E; no DLTs) was 200 mg Q3W (no dose-expansion part was initiated). No new safety signals were identified. In groups A, B, C, and E, the overall response rates were 57.6%, 55.3%, 51.5%, and 57.1%, respectively. Group B compared with other groups had the longest median progression-free survival (10.4 months vs. 6.2–7.5 months), overall survival (29.7 months vs. 16.1–21.0 months), and duration of response (30.1 months vs. 6.0-8.2 months). Conclusions The combination of spartalizumab and PDC, with or without canakinumab, was well tolerated across treatment groups. The antitumor activity across treatment groups was comparable with that of pembrolizumab and pemetrexed combination. Canakinumab did not appear to improve the antitumor activity when combined with spartalizumab, pemetrexed and cisplatin. Trial registration The trial was registered in Clinicaltrials.gov with identifier no. NCT03064854. Date of Registration: 06 February 2017. |
| format | Article |
| id | doaj-art-49d4a4474e494f5081ff231d7fc7b4f8 |
| institution | OA Journals |
| issn | 1471-2407 |
| language | English |
| publishDate | 2024-10-01 |
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| series | BMC Cancer |
| spelling | doaj-art-49d4a4474e494f5081ff231d7fc7b4f82025-08-20T02:22:29ZengBMCBMC Cancer1471-24072024-10-0124111110.1186/s12885-024-12841-2Spartalizumab in combination with platinum-doublet chemotherapy with or without canakinumab in patients with PD-L1-unselected, metastatic NSCLCArmando Santoro0Garrido Pilar1Daniel S.W. Tan2Jon Zugazagoitia3Frances A. Shepherd4Alessandra Bearz5Fabrice Barlesi6Tae Min Kim7Tobias R. Overbeck8Enriqueta Felip9Can Cai10Simantini Eddy11Tracey McCulloch12Eric S. Schaefer13Department of Biomedical Sciences, Humanitas UniversityDepartment of Medical Oncology, Hospital Ramón Y CajalDepartment of Medical Oncology, National Cancer Center SingaporeDepartment of Medical Oncology, University Hospital 12 de OctubreDepartment of Medical Oncology and Hematology, Princess Margaret Cancer CentreDepartment of Medical Oncology, Centro di Riferimento Oncologico - CRODepartment of Multidisciplinary Oncology and Therapeutic Innovations, Aix Marseille University, CNRS, INSERM, CRCM, APHM, CEPCM, CLIPDepartment of Internal Medicine, Seoul National University HospitalDepartment of Hematology and Medical Oncology, University Medical Center GöttingenDepartment of Medical Oncology Service, Vall d’Hebron University Hospital and Vall d’Hebron Institute of OncologyNovartis Pharmaceuticals CorporationNovartis Pharmaceuticals CorporationNovartis Pharma AGDepartment of Medical Oncology, Highlands Oncology GroupAbstract Background Despite promising outcomes of treatment with anti-programmed cell death (PD)-1/PD-ligand (L)1 agents in combination with platinum-doublet chemotherapy (PDC) in the first-line setting, a significant unmet medical need remains in patients with PD-L1-unselected non-small cell lung cancer (NSCLC). Methods This multicenter, open-label, phase 1b study comprising dose-confirmation and dose-expansion parts investigated the combination of spartalizumab and various PDC regimens, with or without canakinumab, in treatment-naïve patients with PD-L1-unselected, metastatic NSCLC. The primary objectives were to determine maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of spartalizumab, with or without canakinumab, in combination with PDC in the dose-confirmation part and antitumor activity of spartalizumab in the dose-expansion part. Results The MTD/RDE of spartalizumab was 300 mg every 3 weeks (Q3W) when administered with either gemcitabine (1250 mg/m2)/cisplatin (75 mg/m2) (group A; no dose-limiting toxicities [DLTs]), pemetrexed (500 mg/m2)/cisplatin (group B; 2 DLTs: grade 2 posterior reversible encephalopathy syndrome and grade 4 hyponatremia), or paclitaxel (200 mg/m2)/carboplatin area under the curve 6 min*mg/mL (group C; 1 DLT: grade 4 neutropenic colitis). The RDE of canakinumab combined with spartalizumab and pemetrexed/cisplatin (group E; no DLTs) was 200 mg Q3W (no dose-expansion part was initiated). No new safety signals were identified. In groups A, B, C, and E, the overall response rates were 57.6%, 55.3%, 51.5%, and 57.1%, respectively. Group B compared with other groups had the longest median progression-free survival (10.4 months vs. 6.2–7.5 months), overall survival (29.7 months vs. 16.1–21.0 months), and duration of response (30.1 months vs. 6.0-8.2 months). Conclusions The combination of spartalizumab and PDC, with or without canakinumab, was well tolerated across treatment groups. The antitumor activity across treatment groups was comparable with that of pembrolizumab and pemetrexed combination. Canakinumab did not appear to improve the antitumor activity when combined with spartalizumab, pemetrexed and cisplatin. Trial registration The trial was registered in Clinicaltrials.gov with identifier no. NCT03064854. Date of Registration: 06 February 2017.https://doi.org/10.1186/s12885-024-12841-2CanakinumabNSCLCPD-L1Platinum-doublet chemotherapySpartalizumab |
| spellingShingle | Armando Santoro Garrido Pilar Daniel S.W. Tan Jon Zugazagoitia Frances A. Shepherd Alessandra Bearz Fabrice Barlesi Tae Min Kim Tobias R. Overbeck Enriqueta Felip Can Cai Simantini Eddy Tracey McCulloch Eric S. Schaefer Spartalizumab in combination with platinum-doublet chemotherapy with or without canakinumab in patients with PD-L1-unselected, metastatic NSCLC BMC Cancer Canakinumab NSCLC PD-L1 Platinum-doublet chemotherapy Spartalizumab |
| title | Spartalizumab in combination with platinum-doublet chemotherapy with or without canakinumab in patients with PD-L1-unselected, metastatic NSCLC |
| title_full | Spartalizumab in combination with platinum-doublet chemotherapy with or without canakinumab in patients with PD-L1-unselected, metastatic NSCLC |
| title_fullStr | Spartalizumab in combination with platinum-doublet chemotherapy with or without canakinumab in patients with PD-L1-unselected, metastatic NSCLC |
| title_full_unstemmed | Spartalizumab in combination with platinum-doublet chemotherapy with or without canakinumab in patients with PD-L1-unselected, metastatic NSCLC |
| title_short | Spartalizumab in combination with platinum-doublet chemotherapy with or without canakinumab in patients with PD-L1-unselected, metastatic NSCLC |
| title_sort | spartalizumab in combination with platinum doublet chemotherapy with or without canakinumab in patients with pd l1 unselected metastatic nsclc |
| topic | Canakinumab NSCLC PD-L1 Platinum-doublet chemotherapy Spartalizumab |
| url | https://doi.org/10.1186/s12885-024-12841-2 |
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