Novartis top-line results for CANOPY-1 Phase III study support further evaluation of canakinumab in lung cancer
Novartis announced today that the CANOPY-1 Phase III study did not demonstrate the statistically significant primary endpoints of overall survival (OS) and?progression-free survival (PFS) in?patients treated with?canakinumab (ACZ885) combined?with pembrolizumab plus platinum-based doublet chemotherapy,?compared to patients receiving placebo in combination with pembrolizumab plus platinum-based doublet chemotherapy1. The trial data, however, showed potentially clinically meaningful improvements in both PFS and OS in pre-specified subgroups of patients based on the baseline inflammatory biomarker, hs-CRP, as well as other biomarker-defined subgroups. These data support further evaluation of canakunimab in lung cancer.
?CANOPY-1 provides critical insights into the treatment of this devastating disease, and we will continue to analyze the data and conclusions, as well as their potential clinical implications,??said John Tsai, MD, Head of Global Drug Development and Chief Medical Officer, Novartis. ?While this trial did not confirm the benefit for all patients we hoped for, we are energized by the overall CANOPY-1 findings as they support our commitment to continue studying canakinumab in lung cancer. We share our gratitude and thanks to the CANOPY-1 study patients and clinical investigators for their partnership.?
Novartis and investigators are collaborating on further data analysis and will present the full dataset at an upcoming medical meeting. The company is continuing with the evaluation of canakinumab in lung cancer, and is applying findings to the overall lung cancer development plan.
The?comprehensive CANOPY?clinical trial program continues with CANOPY-A, a?Phase III study investigating canakinumab as an adjuvant therapy (after surgery)2, and CANOPY-N, a Phase II study in the neoadjuvant setting (before surgery)5.?Enrollment for both trials is ongoing2,5. Patients in the CANOPY-A trial more closely reflect the earlier CANTOS study population than those in the CANOPY-1 trial2,3,4. CANTOS was the first study to show that blocking the IL-1? inflammatory signal may potentially reduce lung cancer?s incidence and mortality3.
Canakinumab is a potential first-in-class interleukin-1beta (IL-1?) inhibitor of the Pro-Tumor Inflammation (PTI) pathway in NSCLC6. PTI, which enables tumor development by driving cancer-causing processes and suppressing anti-tumor immune responses, is one of the potential hallmarks of cancer and targets in NSCLC3,6. Novartis is developing other potential PTI pathway inhibitors, which are at various stages of development, including gevokizumab7,8.
About canakinumab (ACZ885)
Canakinumab is a?human monoclonal antibody that binds with high affinity and selectivity to human interleukin-1beta (IL-1?) and?neutralizes IL-1? activity by blocking its interaction with?its receptors9,10.?By neutralizing IL-1?,?preliminary evidence suggests that?canakinumab may inhibit Pro-Tumor Inflammation (PTI) to 1) enhance anti-tumor immune response; 2) reduce tumor cell proliferation, survival, and invasiveness; and 3) impair angiogenesis11.?PTI enables tumor development by driving cancer-causing processes and?suppressing anti-tumor immune responses3,6.?Canakinumab is a potential first-in-class?IL-1ߠinhibitor of the PTI pathway?in?NSCLC6.
About the CANOPY?program
Novartis launched the CANOPY study program after observing?significantly?lower than expected rates of lung?cancer?mortality?among patients in the Phase III cardiovascular CANTOS trial. The CANTOS trial evaluated canakinumab as a secondary prevention measure for cardiovascular events in patients following a heart attack3,11. Patients in the CANTOS trial also were at high risk for inflammatory cancers, like lung cancer, due to advanced age, smoking history, and other clinical risk factors3,11. Based on these findings,?Novartis launched?three large-scale, randomized,?Phase III clinical trials?and a Phase II?clinical?trial?to investigate canakinumab as a potential treatment option in non-small cell lung cancer?(NSCLC).
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- CANOPY-A (NCT03447769)?is a double-blind, placebo-controlled Phase III trial studying canakinumab in the adjuvant setting following surgical resection and cisplatin-based chemotherapy, if required2.?The adjuvant study is designed to determine if treatment with canakinumab can prevent cancer relapse2.
- CANOPY-N (NCT03968419)?is a Phase II neoadjuvant trial evaluating canakinumab either as monotherapy or in combination with pembrolizumab among patients with?resectable?NSCLC prior to their planned surgery5.
- CANOPY-1?(NCT03631199)?was?a double-blind, placebo-controlled Phase III trial?evaluating canakinumab as a first-line treatment for locally advanced or metastatic NSCLC in combination with?pembrolizumab?and platinum-based?doublet chemotherapy4. As reported today, the trial did not met its primary endpoints of overall survival (OS) and progression-free survival (PFS)1.
- CANOPY-2 (NCT03626545)?was?a double-blind, placebo-controlled Phase III trial?investigating the role of canakinumab?in combination with the chemotherapy agent docetaxel?in second- or?third-line therapy versus?docetaxel?alone in NSCLC12. In March 2021, Novartis announced that the trial did not meet its primary endpoint, and data were presented at the European Society of Medical Oncology (ESMO) 2021 Congress13.
- Novartis Data on File
- ClinicalTrials.gov. Brief Title: Study of Efficacy and Safety of Canakinumab as Adjuvant Therapy in Adult Subjects With Stages AJCC/UICC v. 8 II-IIIA and IIIB (T>5cm N2) Completely Resected Non-small Cell Lung Cancer Acronym: CANOPY-A (Canopy-A). Available at:?https://www.clinicaltrials.gov/ct2/show/NCT03447769. Accessed on September 10, 2021.
- Ridker PM, Thuren T, Zalewski A, et al. Interleukin-1? inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011;162:597?605.
- ClinicalTrials.gov. Study of Efficacy and Safety of Pembrolizumab Plus Platinum-based Doublet Chemotherapy With or Without Canakinumab in Previously Untreated Locally Advanced or Metastatic Non-squamous and Squamous NSCLC Subjects (CANOPY-1). Available at:?https://clinicaltrials.gov/ct2/show/NCT03631199. Accessed on September 10, 2021.
- ClinicalTrials.gov. A Randomized, Open-label, Phase II Study of Canakinumab or Pembrolizumab as Monotherapy or in Combination as Neoadjuvant Therapy in Subjects With Resectable Non-small Cell Lung Cancer (CANOPY-N). Available at:?https://clinicaltrials.gov/ct2/show/NCT03968419. Accessed on September 10, 2021.
- Lu H, Ouyang W, Huang C. Inflammation, a key event in cancer development.?Mol Cancer Res. 2006;4(4):221-233.
- ClinicalTrials.gov. Gevokizumab With Standard of Care Anti-cancer Therapies for Metastatic Colorectal, Gastroesophageal, and Renal Cancers. Available at:?https://clinicaltrials.gov/ct2/show/NCT03798626. Accessed September 10, 2021.
- Jayaraman. P. Targeting IL-1? pathway for cancer immunotherapy. Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30.
- Dhimolea E, mAbs 2010;2:3?13; 3. Ilaris [Prescribing Information T2016-102].
- Rondeau JM, Ramage P, Zurini M, Gram H. The molecular mode of action and species specificity of canakinumab, a human monoclonal antibody neutralizing IL-1?. MAbs. 2015;7(6):1151-1160.
- Novartis data on file: Clinical Trial Protocol CACZ885M2301.
- ClinicalTrials.gov. Phase III Study Evaluating Efficacy and Safety of Canakinumab in Combination With Docetaxel in Adult Subjects With Non-small Cell Lung Cancers as a Second or Third Line Therapy (CANOPY-2). Available at:?https://clinicaltrials.gov/ct2/show/NCT03626545. Accessed on September 10, 2021.
- Paz-Ares, L. Canakinumab (CAN) + docetaxel (DTX) for the second- or third-line (2/3L) treatment of advanced non-small cell lung cancer (NSCLC): CANOPY-2 phase III results. European Society of Clinical Oncology 2021. Oral Presentation.
- World Health Organization. Cancer. Available at:?https://www.who.int/news-room/fact-sheets/detail/cancer. Accessed on September 10, 2021.
- Lemjabbar-Alaoui H, Hassan O, Yang UW, et al. Lung cancer: biology and treatment options.?Biochim Biophys Acta. 2015. 1856(2):189-210.
- American Cancer Society. About Lung Cancer. Available at?https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lung-cancer.html. Accessed September 10, 2021.
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Novartis Media Relations E-mail:?media.relations@novartis.comAnja von Treskow Novartis External Communications +41 61 324 2279 (direct) +41 79 392 8697 (mobile) anja.von_treskow@novartis.com Julie Masow Novartis US External Communications +1 862 579 8456 Julie.masow@novartis.com | Mary Curtin Creaser Director Global Oncology Communications, Solid Tumors +1 862 345-4102 (mobile) mary.curtin_creaser@novartis.com |
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