Novartis looks for silver lining in $2B canakinumab repurposing after 2nd lung cancer failure

Novartis
Despite the two failures in metastatic lung cancer, Novartis is continuing with the phase 3 CANOPY-A trial, testing canakinumab as an adjuvant therapy for preventing cancer relapse following surgery and chemo. (Novartis)

Is autoinflammatory disease treatment Ilaris a potential new therapy for non-small cell lung cancer (NSCLC)? After two pivotal trial failures, the answer seems to be no; but Novartis is still seeing a glimmer of hope.

Adding Ilaris, or canakinumab, to Merck’s Keytruda and platinum-based chemotherapy couldn’t extend the lives of newly diagnosed NSCLC patients, Novartis said Monday. The experimental regimen also failed to show a benefit in slowing tumor progression over the standard immunotherapy-chemo combo.

The latest trial flop comes on top of a defeat revealed in March for previously treated patients. Still, Novartis said the data support further evaluation of Ilaris in lung cancer.

In the previous CANOPY-2 trial of second- or third-line NSCLC, the addition of Ilaris to the chemotherapy docetaxel also failed to pare down the risk of death or disease progression. Patients on the Ilaris-chemo cocktail lived a median 10.5 months, compared with 11.3 months for solo chemo, according to data presented at the recent European Society for Medical Oncology annual meeting.

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In the CANOPY-1 trial among first-line NSCLC patients, investigators noted “potentially clinically meaningful” improvements in both disease progression and overall survival among prespecified subgroups of patients with certain biomarkers, Novartis said, including an inflammation indicator called hs-CRP.

Ilaris targets IL-1beta and has been approved to treat several inflammatory diseases, including systemic juvenile idiopathic arthritis. Novartis first noticed the drug’s anticancer potential in the phase 3 Cantos trial, which tested the med for prevention of recurrent cardiovascular events. There, patients who got Ilaris showed a significantly lower rate of lung cancer death.

Despite the two failures in metastatic NSCLC, Novartis is continuing with the phase 3 CANOPY-A trial, testing Ilaris as a so-called adjuvant therapy for preventing cancer relapse following surgery and chemo. Patients in that study more closely reflect those in the Cantos cardiovascular study than those in CANOPY-1, Novartis argued.

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A phase 2 trial dubbed CANOPY-N is evaluating Ilaris either by itself or in combo with Keytruda for neoadjuvant use, or before a planned surgery.

Jefferies analyst Peter Welford has put canikunumab’s peak sales potential in NSCLC at $2 billion but noted that both the first-line and second-line indications were high-risk. Instead, he has pegged the drug’s probability of success in the field at 40%, mainly related to the perioperative settings.

Novartis believes that by inhibiting IL-1beta, Ilaris could inhibit protumor inflammation while enhancing antitumor immune response and that it could also reduce tumor cell proliferation and reduce the formation of blood vessels that feed valuable nutrients to tumors.

The role of inflammation in cancer is complex, Welford said in a note in March after the negative CANOPY2 readout. “Reducing inflammation with anti-IL1beta, canakinumab, may have a greater impact earlier in the course of the disease,” he wrote, adding that failure in the metastatic setting had little bearing on the chances of success in the adjuvant setting.