On October 25, 2021 Novartis reported 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 (Press release, Novartis, OCT 25, 2021, View Source [SID1234591880]). 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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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-1β inflammatory signal may potentially reduce lung cancer’s incidence and mortality3.

Canakinumab is a potential first-in-class interleukin-1beta (IL-1β) 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-1β) and neutralizes IL-1β activity by blocking its interaction with its receptors9,10. By neutralizing IL-1β, 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-1β inhibitor 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).

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) (Free ESMO Whitepaper) 2021 Congress13.
Novartis and lung cancer
Lung cancer is one of the most common cancers worldwide, accounting for more than 2 million new cases diagnosed each year14. More people die of lung cancer every year than any other cancer14. There are two main types of lung cancer—small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC)15. NSCLC accounts for approximately 85% of lung cancer diagnoses14,16.

Novartis is committed to working with the scientific and medical communities to reimagine the treatment of lung cancer and pursue advances in medicine that could extend the survival of people living with lung cancer. With one of the most diverse lung cancer development programs in the industry, Novartis is: developing experimental therapies that block cancer growth; learning more about ways to activate the body’s immune system; increasing understanding of the relationship between chronic inflammation and tumor growth and progression; and exploring the potential for advanced nuclear medicine to fight the disease. As part of this continuing and broad commitment to targeting lung cancer, data from CANOPY-1 will be evaluated and used to inform canakinumab’s future development program, including potential combination studies with tislelizumab.