Canakinumab’s cancer career ends with a whimper
Novartis's latest failure, in adjuvant lung cancer, heaps more doubt on a rival approach from Cantargia.
Five years ago, intriguing findings in a cardiovascular study set Novartis along a path to discover whether its IL-1 inhibitor canakinumab could have utility in lung cancer. Now that journey is over, with the project’s third and final phase 3 cancer failure, in the Canopy-A study in the adjuvant setting.
Unfortunately, Novartis did not investigate whether, as suggested by the original Cantos study, canakinumab prevented lung cancer – a question that now might never be answered. The Swiss group’s attention will now turn to other readouts, but a rival in the IL-1 space, Cantargia, is not so lucky.
Cantargia, whose entire pipeline is built around this mechanism, sank 5% today. That company recently presented data at Asco with its lead project, nadunolimab (CAN04), but these do not shed too much light on its chances.
On the face of it, a 33% immune overall response rate (iORR) with nadunolimab plus Abraxane and gemcitabine in first-line pancreatic cancer in the Canfour study look promising, on a cross-trial basis eclipsing the 23% ORR seen with Abraxane plus gemcitabine alone in this setting.
However, Cantargia’s use of iORR (referring to use of iRecist rather than Recist criteria) raises questions about whether its data are comparable to those for standard of care on a cross-trial basis.
Data from Canfour in NSCLC were even harder to interpret: some patients had previously received Keytruda first line, a difficult population to handicap given the lack of data in post-PD-(L)1 patients.
Cantargia is also trialling nadunolimab plus Keytruda in patients who had progressed on checkpoint inhibitors, in the phase 1 Cirifour study. So far the company has seen one immune partial response among 15 patients.
|Anti-IL-1 projects in development for cancer|
|Project||Trial details & readouts||Result & note|
|Canakinumab (Novartis)||Canopy-2, 2L NSCLC||Failed Mar 2021|
|Canopy-1, 1L NSCLC + Keytruda + chemo||Failed Oct 2021|
|Canopy-A, adjuvant NSCLC||Failed Aug 2022|
|Ph2 Canopy-N, neoadjuvant NSCLC +/- Keytruda||Ended Apr 2022; no results|
|Gevokizumab (Novartis)||Ph2* 1L CRC||Started Jan 2022|
|Ph1 1/2L CRC, 2L GEC; 2/3L RCC||Started Jan 2019|
|Ph1/2 Canfour in 1L PDAC + Abraxane + gemcitabine; NSCLC + cisplatin+ gemcitabine, previous Keytruda allowed||Interim data at Asco 2022:
1L PDAC: 33% iORR (23% ORR seen with Abraxane + gemcitabine);
NSCLC: ORR 53% (no clear comparator for post-PD-(L)1 NSCLC pts)
|Ph1 Cirifour + Keytruda in NSCLC, H&N & melanoma post-Keytruda||Interim data at Asco 2022: iORR 7% (no clear comparator for post-PD-(L)1 NSCLC pts)|
|Ph1/2 Cestafour chemo combo in NSCLC, BTC, CRC|
|Ph1/2 Trifour + gemcitabine + carboplatin in TNBC|
|Ph1 Capafour + Folfirinox in 1L PDAC|
|*Investigator-sponsored trial; BTC=biliary tract cancer; CRC=colorectal cancer; GEC=gastroesophageal cancer; H&N=head and neck cancer; iORR=immune overall response rate; NSCLC=non-small cell lung cancer; PDAC=pancreatic ductal adenocarcinoma; RCC=renal cell carcinoma; TNBC=triple-negative breast cancer.|
As for Novartis, it was probably right – scientifically at least – to investigate the canakinumab cancer signal, but its decision to evaluate cancer treatment, rather than prevention, is puzzling.
The size of a preventative cancer study might have been a factor here, but the company now looks like it has merely thrown good money after bad: the latest cancer flops come after the FDA rejected canakinumab for cardiovascular use in 2018, following mixed data in Cantos, which enrolled over 10,000 patients.
Canakinumab is marketed as Ilaris for several rare diseases, and last year brought in just over $1bn.
The big remaining readouts for Novartis for 2022 involve the pivotal Apply-PNH trial of the complement factor B inhibitor iptacopan in paroxysmal nocturnal haemoglobinuria, and the phase 3 PSMAfore study of its radioligand therapy Pluvicto in pre-taxane metastatic castrate-resistant prostate cancer. The latter drug is already approved for mCRPC, but after taxane-based chemotherapy.
This story has been updated to clarify the definition of iORR.