CANOPY-N: A Phase 2 Study of Canakinumab or Pembrolizumab, Alone or in Combination, as Neoadjuvant Therapy in Patients With Resectable, Stage IB–IIIA NSCLC
Introduction: Canakinumab is a human monoclonal anti–interleukin-1β antibody with the potential to enhance the activity of programmed death-ligand 1 inhibitors by inhibiting protumor inflammation. Methods: CANOPY-N was a randomized, phase 2 study to evaluate safety and efficacy of neoadjuvant canaki...
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2025-08-01
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| Series: | JTO Clinical and Research Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364325000761 |
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| author | Jay M. Lee, MD Jean-Louis Pujol, MD, PhD Jun Zhang, MD, PhD Oleg Leonov, MD, PhD Masahiro Tsuboi, MD, PhD Edward S. Kim, MD, MBA Calvin Ng, MD Nicolas Moreno-Mata, MD, PhD Amy Cummings, MD, PhD Ilhan Hacibekiroglu, MD Abidin Sehitogullari, MD Nirmal Veeramachaneni, MD Cathy Spillane, PhD Jiawei Duan, PhD Claudia Bossen, PhD Alexander Savchenko, MD, PhD Chiara Lobetti-Bodoni, MD, PhD Tony Mok, MD Pilar Garrido, MD |
| author_facet | Jay M. Lee, MD Jean-Louis Pujol, MD, PhD Jun Zhang, MD, PhD Oleg Leonov, MD, PhD Masahiro Tsuboi, MD, PhD Edward S. Kim, MD, MBA Calvin Ng, MD Nicolas Moreno-Mata, MD, PhD Amy Cummings, MD, PhD Ilhan Hacibekiroglu, MD Abidin Sehitogullari, MD Nirmal Veeramachaneni, MD Cathy Spillane, PhD Jiawei Duan, PhD Claudia Bossen, PhD Alexander Savchenko, MD, PhD Chiara Lobetti-Bodoni, MD, PhD Tony Mok, MD Pilar Garrido, MD |
| author_sort | Jay M. Lee, MD |
| collection | DOAJ |
| description | Introduction: Canakinumab is a human monoclonal anti–interleukin-1β antibody with the potential to enhance the activity of programmed death-ligand 1 inhibitors by inhibiting protumor inflammation. Methods: CANOPY-N was a randomized, phase 2 study to evaluate safety and efficacy of neoadjuvant canakinumab (200 mg subcutaneous once every three weeks) and pembrolizumab (200 mg intravenous once every three weeks), either in combination or alone, in patients with early-stage (stage Ib–IIIa) NSCLC. The primary end point was major pathologic response (MPR) rates (≤10% of residual tumor cells) by central pathology review in the arms containing canakinumab. Secondary end points included overall response rates, safety, pharmacokinetics, surgical feasibility rates, and MPR rate in the pembrolizumab arm. The impact of treatment on surgical outcomes was assessed as an exploratory outcome. Results: In total, 88 patients were enrolled: 35 to the canakinumab arm, 35 to the canakinumab + pembrolizumab arm, and 18 to the pembrolizumab arm. One patient (2.9%) in the canakinumab arm (95% confidence interval [CI]: 0.07–14.92), six patients (17.1%) in the canakinumab + pembrolizumab arm (95% CI: 6.56–33.65), and three patients (16.7%) in the pembrolizumab arm (95% CI: 3.58–41.42) achieved MPR. No unexpected safety signals were observed. Of the 84 patients (95.5%) who underwent operation, the prespecified 6-week window was achieved for 72 patients (85.7%). Conclusions: Neoadjuvant treatment with canakinumab alone or combined with pembrolizumab did not improve MPR rates compared with pembrolizumab alone. No unexpected safety signals were observed and canakinumab did not adversely affect surgical outcomes. Intraoperative perihilar or perilobular fibrosis after neoadjuvant immunotherapy was rare. |
| format | Article |
| id | doaj-art-dfba2d0827924a368ac99bee35e76b99 |
| institution | DOAJ |
| issn | 2666-3643 |
| language | English |
| publishDate | 2025-08-01 |
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| series | JTO Clinical and Research Reports |
| spelling | doaj-art-dfba2d0827924a368ac99bee35e76b992025-08-20T02:56:32ZengElsevierJTO Clinical and Research Reports2666-36432025-08-016810085910.1016/j.jtocrr.2025.100859CANOPY-N: A Phase 2 Study of Canakinumab or Pembrolizumab, Alone or in Combination, as Neoadjuvant Therapy in Patients With Resectable, Stage IB–IIIA NSCLCJay M. Lee, MD0Jean-Louis Pujol, MD, PhD1Jun Zhang, MD, PhD2Oleg Leonov, MD, PhD3Masahiro Tsuboi, MD, PhD4Edward S. Kim, MD, MBA5Calvin Ng, MD6Nicolas Moreno-Mata, MD, PhD7Amy Cummings, MD, PhD8Ilhan Hacibekiroglu, MD9Abidin Sehitogullari, MD10Nirmal Veeramachaneni, MD11Cathy Spillane, PhD12Jiawei Duan, PhD13Claudia Bossen, PhD14Alexander Savchenko, MD, PhD15Chiara Lobetti-Bodoni, MD, PhD16Tony Mok, MD17Pilar Garrido, MD18UCLA Health, Los Angeles, California; Corresponding author. Address for correspondence: Jay M. Lee, MD, UCLA Division of Thoracic Surgery, Box 957313, Room 64-128 CHS, 10833 Le Conte Ave, Los Angeles 90095-7313, California.Centre Hospitalier Universitaire de Montpellier, Montpellier, FranceUniversity of Kansas Medical Center, Kansas City, KansasClinical Oncological Dispensary, Omsk, RussiaNational Cancer Center Hospital East, Kashiwa, JapanCity of Hope National Medical Center, Irvine, CaliforniaChinese University of Hong Kong, Hong Kong, People's Republic of ChinaHospital Universitario Ramón y Cajal, Madrid, SpainUCLA Health, Los Angeles, CaliforniaSakarya University, Sakarya, TurkeySakarya University, Sakarya, TurkeySaint Louis University School of Medicine, Saint Louis, MissouriNovartis Pharmaceuticals Corporation, Dublin, IrelandNovartis Pharmaceuticals Corporation, Dublin, IrelandNovartis Pharma AG, Basel, SwitzerlandNovartis Pharmaceuticals Corporation, Cambridge, MassachusettsNovartis Pharma AG, Basel, SwitzerlandChinese University of Hong Kong, Hong Kong, People's Republic of ChinaHospital Universitario Ramón y Cajal, Madrid, SpainIntroduction: Canakinumab is a human monoclonal anti–interleukin-1β antibody with the potential to enhance the activity of programmed death-ligand 1 inhibitors by inhibiting protumor inflammation. Methods: CANOPY-N was a randomized, phase 2 study to evaluate safety and efficacy of neoadjuvant canakinumab (200 mg subcutaneous once every three weeks) and pembrolizumab (200 mg intravenous once every three weeks), either in combination or alone, in patients with early-stage (stage Ib–IIIa) NSCLC. The primary end point was major pathologic response (MPR) rates (≤10% of residual tumor cells) by central pathology review in the arms containing canakinumab. Secondary end points included overall response rates, safety, pharmacokinetics, surgical feasibility rates, and MPR rate in the pembrolizumab arm. The impact of treatment on surgical outcomes was assessed as an exploratory outcome. Results: In total, 88 patients were enrolled: 35 to the canakinumab arm, 35 to the canakinumab + pembrolizumab arm, and 18 to the pembrolizumab arm. One patient (2.9%) in the canakinumab arm (95% confidence interval [CI]: 0.07–14.92), six patients (17.1%) in the canakinumab + pembrolizumab arm (95% CI: 6.56–33.65), and three patients (16.7%) in the pembrolizumab arm (95% CI: 3.58–41.42) achieved MPR. No unexpected safety signals were observed. Of the 84 patients (95.5%) who underwent operation, the prespecified 6-week window was achieved for 72 patients (85.7%). Conclusions: Neoadjuvant treatment with canakinumab alone or combined with pembrolizumab did not improve MPR rates compared with pembrolizumab alone. No unexpected safety signals were observed and canakinumab did not adversely affect surgical outcomes. Intraoperative perihilar or perilobular fibrosis after neoadjuvant immunotherapy was rare.http://www.sciencedirect.com/science/article/pii/S2666364325000761NSCLCNeoadjuvant treatmentMonoclonal antibodies |
| spellingShingle | Jay M. Lee, MD Jean-Louis Pujol, MD, PhD Jun Zhang, MD, PhD Oleg Leonov, MD, PhD Masahiro Tsuboi, MD, PhD Edward S. Kim, MD, MBA Calvin Ng, MD Nicolas Moreno-Mata, MD, PhD Amy Cummings, MD, PhD Ilhan Hacibekiroglu, MD Abidin Sehitogullari, MD Nirmal Veeramachaneni, MD Cathy Spillane, PhD Jiawei Duan, PhD Claudia Bossen, PhD Alexander Savchenko, MD, PhD Chiara Lobetti-Bodoni, MD, PhD Tony Mok, MD Pilar Garrido, MD CANOPY-N: A Phase 2 Study of Canakinumab or Pembrolizumab, Alone or in Combination, as Neoadjuvant Therapy in Patients With Resectable, Stage IB–IIIA NSCLC JTO Clinical and Research Reports NSCLC Neoadjuvant treatment Monoclonal antibodies |
| title | CANOPY-N: A Phase 2 Study of Canakinumab or Pembrolizumab, Alone or in Combination, as Neoadjuvant Therapy in Patients With Resectable, Stage IB–IIIA NSCLC |
| title_full | CANOPY-N: A Phase 2 Study of Canakinumab or Pembrolizumab, Alone or in Combination, as Neoadjuvant Therapy in Patients With Resectable, Stage IB–IIIA NSCLC |
| title_fullStr | CANOPY-N: A Phase 2 Study of Canakinumab or Pembrolizumab, Alone or in Combination, as Neoadjuvant Therapy in Patients With Resectable, Stage IB–IIIA NSCLC |
| title_full_unstemmed | CANOPY-N: A Phase 2 Study of Canakinumab or Pembrolizumab, Alone or in Combination, as Neoadjuvant Therapy in Patients With Resectable, Stage IB–IIIA NSCLC |
| title_short | CANOPY-N: A Phase 2 Study of Canakinumab or Pembrolizumab, Alone or in Combination, as Neoadjuvant Therapy in Patients With Resectable, Stage IB–IIIA NSCLC |
| title_sort | canopy n a phase 2 study of canakinumab or pembrolizumab alone or in combination as neoadjuvant therapy in patients with resectable stage ib iiia nsclc |
| topic | NSCLC Neoadjuvant treatment Monoclonal antibodies |
| url | http://www.sciencedirect.com/science/article/pii/S2666364325000761 |
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